Recently, MYBL2 is frequently found to be overexpressed and associated with poor patient outcome in breast cancer, colorectal cancer, bladder carcinoma, hepatocellular carcinoma, neuroblastoma and acute myeloid leukemia. In view of the fact that there is an association between MYBL2 expression and the clinicopathological features of human cancers, most studies reported so far are limited in their sample size, tissue type and discrete outcomes. Furthermore, we need to verify which additional cancer entities are also affected by MYBL2 deregulation and which patients could specifically benefit from using MYBL2 as a biomarker or therapeutic target. We characterized the up-regulated expression level of MYBL2 in a large variety of human cancer via TCGA and oncomine database. Subsequently, we verified the elevated MYBL2 expression effect on clinical outcome using various databases. Then, we investigate the potential pathway in which MYBL2 may participate in and find 4 TFs (transcript factors) that may regulate MYBL2 expression using bioinformatic methods. At last, we confirmed elevated MYBL2 expression can be useful as a biomarker and potential therapeutic target of poor patient prognosis in a large variety of human cancers. Additionally, we find E2F1, E2F2, E2F7 and ZNF659 could interact with MYBL2 promotor directly or indirectly, indicating the four TFs may be the upstream regulator of MYBL2. TP53 mutation or TP53 signaling altered may lead to elevated MYBL2 expression. Our findings indicate that elevated MYBL2 expression represents a prognostic biomarker for a large number of cancers. What's more, patients with both P53 mutation and elevated MTBL2 expression showed a worse survival in PRAD and BRCA.
Citation: Zekun Xin, Yang Li, Lingyin Meng, Lijun Dong, Jing Ren, Jianlong Men. Elevated expression of the MYB proto-oncogene like 2 (MYBL2)-encoding gene as a prognostic and predictive biomarker in human cancers[J]. Mathematical Biosciences and Engineering, 2022, 19(2): 1825-1842. doi: 10.3934/mbe.2022085
[1] | Cherechi Ndukwe, M. Tariq Iqbal, Xiaodong Liang, Jahangir Khan, Lawrence Aghenta . LoRa-based communication system for data transfer in microgrids. AIMS Electronics and Electrical Engineering, 2020, 4(3): 303-325. doi: 10.3934/ElectrEng.2020.3.303 |
[2] | Efthymios N. Lallas . A survey on key roles of optical switching and labeling technologies on big data traffic of Data Centers and HPC environments. AIMS Electronics and Electrical Engineering, 2019, 3(3): 233-256. doi: 10.3934/ElectrEng.2019.3.233 |
[3] | Shahzad Ashraf, Arshad Ahmad, Adnan Yahya, Tauqeer Ahmed . Underwater routing protocols: Analysis of link selection challenges. AIMS Electronics and Electrical Engineering, 2020, 4(3): 234-248. doi: 10.3934/ElectrEng.2020.3.234 |
[4] | Boualem Djehiche, Alain Tcheukam, Hamidou Tembine . Mean-Field-Type Games in Engineering. AIMS Electronics and Electrical Engineering, 2017, 1(1): 18-73. doi: 10.3934/ElectrEng.2017.1.18 |
[5] | Farhan Khan, Sing Kiong Nguang . Dual sensing scheduling algorithm for WSN based road network surveillance. AIMS Electronics and Electrical Engineering, 2021, 5(1): 38-54. doi: 10.3934/electreng.2021003 |
[6] | Vuong Quang Phuoc, Nguyen Van Dien, Ho Duc Tam Linh, Nguyen Van Tuan, Nguyen Van Hieu, Le Thai Son, Nguyen Tan Hung . An optimized LSTM-based equalizer for 100 Gigabit/s-class short-range fiber-optic communications. AIMS Electronics and Electrical Engineering, 2024, 8(4): 404-419. doi: 10.3934/electreng.2024019 |
[7] | Asim Anwar, Boon-Chong Seet, Xue Jun Li . NOMA for V2X under similar channel conditions. AIMS Electronics and Electrical Engineering, 2018, 2(2): 48-58. doi: 10.3934/ElectrEng.2018.2.48 |
[8] | Deven Nahata, Kareem Othman . Exploring the challenges and opportunities of image processing and sensor fusion in autonomous vehicles: A comprehensive review. AIMS Electronics and Electrical Engineering, 2023, 7(4): 271-321. doi: 10.3934/electreng.2023016 |
[9] | B Naresh Kumar, Jai Sukh Paul Singh . Intelligence-based optimized cognitive radio routing for medical data transmission using IoT. AIMS Electronics and Electrical Engineering, 2022, 6(3): 223-246. doi: 10.3934/electreng.2022014 |
[10] | Minglong Zhang, Iek Cheong Lam, Arun Kumar, Kin Kee Chow, Peter Han Joo Chong . Optical environmental sensing in wireless smart meter network. AIMS Electronics and Electrical Engineering, 2018, 2(3): 103-116. doi: 10.3934/ElectrEng.2018.3.103 |
Recently, MYBL2 is frequently found to be overexpressed and associated with poor patient outcome in breast cancer, colorectal cancer, bladder carcinoma, hepatocellular carcinoma, neuroblastoma and acute myeloid leukemia. In view of the fact that there is an association between MYBL2 expression and the clinicopathological features of human cancers, most studies reported so far are limited in their sample size, tissue type and discrete outcomes. Furthermore, we need to verify which additional cancer entities are also affected by MYBL2 deregulation and which patients could specifically benefit from using MYBL2 as a biomarker or therapeutic target. We characterized the up-regulated expression level of MYBL2 in a large variety of human cancer via TCGA and oncomine database. Subsequently, we verified the elevated MYBL2 expression effect on clinical outcome using various databases. Then, we investigate the potential pathway in which MYBL2 may participate in and find 4 TFs (transcript factors) that may regulate MYBL2 expression using bioinformatic methods. At last, we confirmed elevated MYBL2 expression can be useful as a biomarker and potential therapeutic target of poor patient prognosis in a large variety of human cancers. Additionally, we find E2F1, E2F2, E2F7 and ZNF659 could interact with MYBL2 promotor directly or indirectly, indicating the four TFs may be the upstream regulator of MYBL2. TP53 mutation or TP53 signaling altered may lead to elevated MYBL2 expression. Our findings indicate that elevated MYBL2 expression represents a prognostic biomarker for a large number of cancers. What's more, patients with both P53 mutation and elevated MTBL2 expression showed a worse survival in PRAD and BRCA.
A 2-(v,k,λ) design D is a pair (P,B), where P is a set of v points, and B is a set of k-subsets of P called blocks, such that any 2 points are contained in exactly λ blocks. A flag is a point-block pair (α,B) with α∈B. The Fisher's inequality in [8, 1.3.8] shows that the number of blocks is at least v. Design D is said to be non-symmetric if v<b and non-trivial if 2<k<v−1. We always assume D to be non-trivial and non-symmetric in this paper. An automorphism of D is a permutation of P that leaves B invariant. All automorphisms of the design D form a group called the full automorphism group of D, denoted by Aut(D). Let G≤Aut(D). The design D is called point (block, flag)-transitive if G acts transitively on the set of points (blocks, flags) and point-primitive if G acts primitively on P, that is, G does not preserve a partition of P in classes of size c with 1<c<v.
For decades, works have been done on the classification of 2-designs admitting a transitive automorphism group. In 1988, Buekenhout, Delandtsheer, and Doyen first proved in [5] that the flag-transitive automorphism group of a 2-(v,k,1) design must be of affine or almost simple type. Then, the classification of flag-transitive 2-(v,k,1) designs was given in [6] by a six-person team, except for the case of the one-dimensional affine type. In recent years, some researchers have focused on into classifying 2-(v,k,λ) designs with general λ admitting flag-transitive automorphism group, such as [1,3,12,16,25,26,27]. Moreover, some of the works also considered classification of such designs admitting automorphism groups in a weaker condition, namely, block-transitive rather than flag-transitive [21,22,23,24].
The current paper tackles the 2-(v,k,λ) designs where λ is a prime. In [25], Zhang and Chen reduced the flag-transitive, point-primitive automorphism groups of such 2-designs either to the affine type (with an elementary abelian p-group as socle) or to the almost simple type (with a nonabelian simple socle). Hence, it is possible to classify such 2-designs based on the classification of simple groups. The aim of this paper is to consider the case when the socle of the automorphism group G is an exceptional simple group of Lie type. Note that groups G2(2), 2G2(3), 2B2(2), and 2F4(2) are not simple, so they are not under consideration in this work. It is also worth noting that the symmetric 2-designs with exceptional simple socle have been studied in [1,2,20]. The main result of the current paper is the following:
Theorem 1.1. Let D be a non-symmetric 2-(v,k,λ) design with λ prime and G a flag-transitive automorphism group of D. If the socle T of G is an exceptional Lie type simple group in characteristic p, then one of the following holds:
(1) T is 2B2(q) with q=22n+1>2 and (v,k,λ)=(q2+1,q,q−1), where q−1 is a Mersenne prime;
(2) T is G2(q), and (v,k,λ)=(q3(q3−1)2,q32,q+1) where q>2 is even and q+1 is a Fermat prime.
Remark 1.1. For the parameters in Theorem 1.1(1), the design D is described in [26]. For the parameters in Theorem 1.1(2), the existence of such a design remains uncertain at this time.
We begin with some well-established results about the parameters of 2-(v,k,λ) designs and the automorphism groups of them. For any point α, we denote by r the number of blocks that contain α, as it is a constant.
Lemma 2.1. ([8]) For a 2-(v,k,λ) design D, it is well known that
(1) bk=vr;
(2) λ(v−1)=r(k−1);
(3) λv<r2.
Lemma 2.2. ([8,Section 1.2]) Assume that G is an automorphism group of D. Then the flag-transitivity of G is equivalent to one of the following:
(1) G is point-transitive, and the point stabilizer Gα is transitive on all blocks that contain α;
(2) G is block-transitive, and the block stabilizer GB is transitive on the k points in block B.
Lemma 2.3. [7]) Assume that G is a flag-transitive automorphism group of D, and T is the socle of G. Then, we have
(1) r∣|Gα|, where Gα is the point-stabilizer of G;
(2) r∣λdi, where di is any nontrivial subdegree of G.
Assume that λ is a prime. Then either (λ,r)=1 or λ∣r. For the former case, by the results of [26], we immediately obtain the following Lemma:
Lemma 3.1. Assume that G and D satisfy the hypothesis of Theorem 1.1. If (λ,r)=1, then T=2B2(q) with q=22n+1≥8, and D is a 2-(q2+1,q,q−1) design with q−1 a Mersenne prime. In particular, 2n+1 is prime.
Therefore, we always assume λ∣r in the remaining content. Let r0=rλ. We get the following from Lemmas 2.1 and 2.3.
Lemma 3.2. Assume that D is a 2-(v,k,λ) design where λ is a prime divisor of r, and G is a flag-transitive automorphism group of D. Then we have
(1) v<λr20;
(2) r0 divides the greatest common divisor of |Gα|, v−1 and all nontrivial subdegrees of G.
Since G is point-primitive, the point stabilizer Gα is a maximal subgroup of G. In this section, we first deal with the case when Gα is a maximal parabolic subgroup of G.
Lemma 3.3. Assume that T=2B2(q) with q=22n+1>2. Then Gα cannot be the maximal parabolic subgroup of G.
Proof. If Gα is a maximal parabolic subgroup of G, we know that |Gα|=fq2(q−1) with f∣(2n+1) from [19], and hence v=q2+1. Then, according to (1) and (2) in Lemma 2.1 and the fact λ∣r, we further get k−1∣q2 and b=λq2(q2+1)k(k−1). Since G is flag-transitive, Lemma 2.2 implies that |GB|=|G|b=fk(k−1)(q−1)λ. All maximal subgroups of G can be read off from [19], and let M be any one of them with GB≤M. The fact that |GB| divides |M| implies that M is the maximal parabolic subgroup of G, and k(k−1) divides λq2. This forces k=λ, for otherwise k(k−1)∣q2, which is a contradiction. It follows that GB is primitive on B, and so TB is transitive on B. Namely, |TB:Tγ,B|=k for any point γ∈B. On the other hand, since M is parabolic, there exists a point α such that M=Gα. That is to say, TB≤Tα and therefore Tγ,B≤Tγ,α for γ∈B. Since the stabilizer of any two points in 2B2(q) is a cyclic group of order q−1 by [9, p.187], |Tγ,B| divides (q−1). Also, |T:Tγ,α| divides bk by the flag-transitivity of G. It follows that (k−1)∣λ, which holds only when λ=k=2, for it has been proved that k=λ above. This is impossible as D is nontrivial.
Lemma 3.4. Assume that T=2G2(q) with q=32n+1>3. Then Gα cannot be the maximal parabolic subgroup of G.
Proof. If Gα is the maximal parabolic subgroup of G, then we know that |Gα|=fq3(q−1) with f∣(2n+1) from [11], and so v=q3+1. Similar as to Lemma 3.3, we have
b=λv(v−1)k(k−1)=λq3(q3+1)k(k−1) |
and k−1∣q3. Let f1 be a divisor of f such that |GB:TB|=f1. Then by the flag-transitivity of G, we get
|TB|=f(q−1)k(k−1)f1λ. |
Here, we also consider the maximal subgroups M of 2G2(q) such that TB≤M. From [11], either M is parabolic, or M≅Z2×PSL2(q).
If M is a parabolic subgroup, then k(k−1)∣λq3. Since k−1∣q3, we have k∣λ and therefore λ=k. It follows that λ−1∣q3 and λ=3n1+1, which forces λ=k=2, for λ is prime. However, now we get b=q3(q3+1)>(v2), which is obviously impossible. Hence, in the remaining part of the proof, we assume that TB≤Z2×PSL2(q).
According to the list of the maximal subgroups of PSL2(q) in [4, Tables 8.1 and 8.2], TB is isomorphic to a subgroup of Z2×A4, Z2×Dq±1, Z2×([q]:Zq−12) or Z2×PSL2(q0) with qℓ0=q=32n+1. Obviously, the former two cases are impossible as k−1∣q3. Then, if TB≲Z2×([q]:Zq−12), we also have λ=k, a contradiction again. For the last case, the condition that |TB| divides |Z2×PSL2(q0)| forces q0=q, which implies that TB is isomorphic to Z2×PSL2(q) or PSL2(q). Then, by |T:TB|∣b, we have k(k−1)∣q(q+1)λ. This, together with k−1∣q2, implies that k−1∣q when λ≠3, and k−1∣3q when λ=3. Furthermore, the facts that q+1 is the smallest degree of non-trivial action of PSL2(q) since q is an odd power of 3 and that |TB:Tα,B| divides k imply k=q+1. Hence, |TB|=fk(k−1)(q−1)f1λ=q(q2−1)a, with a=1 or 2 when TB is Z2×PSL2(q) or PSL2(q), respectively. It follows that λ∣f when TB is Z2×PSL2(q), or λ=2 when TB is PSL2(q).
Let R be the Ree unital of order q (which is a 2-(q3+1,q+1,1) design). For the former case, let σ be the central involution of Z2×PSL2(q). It can be deduced from [15] that σ fixes a block ℓ of R pointwise and preserves a point-partition Sσ of R∖ℓ into q2−q blocks, each of them invariant by σ. Now, Z2×PSL2(q) induces PSL2(q) on Sσ∪{ℓ}, and PSL2(q) preserves ℓ acting on this one in its natural 2-transitive action of degree q+1. Further, PSL2(q) partitions Sσ into two orbits each of length q2−q2. Thus, ℓ is the unique Z2×PSL2(q)-orbit of points of R of length q+1. Note that k=q+1, which means B=ℓ. This means that |BG|=|ℓG|=q2(q2−q+1) by [6], and so λ=1, which contradicts with λ being prime. For the latter case, the block stabilizer Tℓ for the Ree unital is Z2×PSL2(q), and Z2 fixed all points in ℓ. However, since αTB⊆αTℓ and |αTB|=|αTℓ|=q+1, we have αTB=αTℓ. This means that Z2 fixed all points in B, and so Z2∈TB, an obvious contradiction.
For the remaining possibility of T in T, where
T={2F4(q),3D4(q),G2(q),F4(q),Eϵ6(q),E7(q),E8(q)}, |
we use the following Lemma from [14] to prove that Gα cannot be the maximal parabolic subgroup. Note that in the following we denote by np the p-part of n and np′ the p′-part of n, i.e., np=pt where pt∣n but pt+1∤n, and np′=n/np.
Lemma 3.5. ([14]) Assume that T is a simple group of Lie type in characteristic p and acts on the set of cosets of a maximal parabolic subgroup. Then T has a unique subdegree which is a power of p except when T is Ld(q), Ω+2m(q) (m is odd) or E6(q).
Lemma 3.6. If T∈T, then Gα cannot be a parabolic subgroup of G.
Proof. By Lemma 3.5, for all cases where T∈T∖{E6(q)}, there is a unique subdegree which is a power of p. Then, Lemma 3.2 implies that r0 divides |v−1|p. Since we also have λ divides |Gα|, we can easily check that r0 is too small to satisfy the condition v<λr20. Therefore, we assume that T=E6(q). If G contains a graph automorphism, or Gα∩T is P2 or P4, then there is also a unique subdegree that is a power of p. However, r0 is too small again. If Gα∩T is P3 with type A1A4, we have λ≤q5−1q−1 by λ∣|Gα| and
v=(q3+1)(q4+1)(q9−1)(q6+1)(q4+q2+1)(q−1). |
Moreover, from [1, Proposition 6.3], we know that there exist two nontrivial subdegrees: q13q5−1q−1 and q(q5−1)(q4−1)(q−1)2. Lemma 3.2 then implies that r divides λqq5−1q−1. However, the condition v<λr20 cannot be satisfied again. If Gα∩T is P1 with type D5, then
v=(q8+q4+1)(q9−1)q−1, |
and there exist two nontrivial subdegrees (see [13]): q(q3+1)(q8−1)(q−1) and q8(q4+1)(q5−1)(q−1). It follows that r∣λq(q4+1). This, together with λ∣|Gα|, implies that r2<λ2q2(q4+1)2<λv, which is contradictive with Lemma 2.1.
In this section, we assume that Gα is a non-parabolic maximal subgroup of G.
Lemma 3.7. Assume that G and D satisfy the hypothesis of Theorem 1.1. Then, |G|<|Gα|3.
Proof. From Lemma 2.3, we know that r divides every nontrivial subdegree of G, and so r divides |Gα|. Since v<r2 by (3) of Lemma 2.1, it follows that |G|<|Gα|3.
Lemma 3.7 implies that Gα is a large maximal non-parabolic subgroup of G. The type of Gα can be read from [1, Table 2]. Note that Theorem 1.1(2) just corresponds to the non-parabolic case here, with T=G2(q) and the type of Gα being SLϵ3(q).2.
Lemma 3.8. Assume that G and D satisfy the hypothesis of Theorem 1.1. If T=G2(q) and the type of Gα is SLϵ3(q).2 with ϵ=±, then ϵ=−, T is flag-transitive on D, and the parameters of D are (v,b,r,k,λ)=(q3(q3−1)2,(q+1)(q6−1),(q+1)(q3+1),q32,q+1), where q is even, and λ=q+1 is a Fermat prime.
Proof. It is obvious that |Tα|=2q3(q2−1)(q3−ϵ1), and hence v=12q3(q3+ϵ1). We first deal with the case when q is even. Since G2(2) is not simple (G2(2)≅PSU3(3):2), we assume that q>2. From [17, Section 3, Case 8], we know that r divides λ(q3−ϵ1). Then, the equality λ(v−1)=r(k−1) from Lemma 2.1 implies that there exists an odd integer t dividing (q3−ϵ1) such that
k=t(q3+ϵ2)2+1andr=λ(q3−ϵ1)t. |
Obviously, the fact that k<r implies t<λ. Moreover, by Lemma 2.1 we have
b=λv(v−1)k(k−1)=λq3(q6−1)(q3+ϵ2)4k(k−1)=λq3(q6−1)2kt. | (3.1) |
Note also that (2k,q3−ϵ1)∣3t+ϵ2, (2k,q3+1)∣t+ϵ2, (k,q32)∣t+ϵ1, and therefore (2k,q2−1)∣(t+ϵ2)(3t+ϵ2). Since b is an integer, it follows from (3.1) that k∣λq32(q3−ϵ1)(q3+ϵ1). Hence, we have
t(q3+ϵ2)2+1∣λ(t+ϵ2)(t+ϵ1)(3t+ϵ2). | (3.2) |
Since 3t+ϵ2≤5t, it follows that q3+ϵ2<10λ(t+ϵ2)(t+ϵ1) except when t=1 and ϵ=−. When t≠1, the above together with t<λ further implies that λ cannot be a prime divisor of |Out(T)|, and hence λ divides |SLϵ3(q).2|.
In the following, we prove that t=1. Obviously, t≠2, for t is odd. When t≥3, we have rλ≤13(q3−ϵ1) and 3t2<λ by t(q3+ϵ2)2<k≤r≤λ(q3−ϵ1)3. Now, assume that λ∣k. Then λ divides (2q3(q2−1)(q3−ϵ1),2k), and it follows that λ∣4(t+ϵ1)(t+ϵ2)(3t+ϵ2)2. Since 32t<λ, we have λ=3t+ϵ2, or ϵ=+ and λ=3t+22. If λ=3t+2ϵ, then k<r forces (t,λ,ϵ)=(5,17,+), (5,13,−), (3,11,+), (3,7,−), or (1,5,+). Note that k∣λ(t+ϵ2)(t+ϵ1)(3t+ϵ2), and we check each case and know that it is impossible. If λ=3t+22, then we get (t,λ)=(4,7), which can be ruled out similarly. Hence, λ∤k, and it follows (3.2) that t>q. On the other hand, since |T:TB|∣b, there exists an integer f1 dividing f such that f1|T:TB|=b and
|TB|=2f1q3(q2−1)kλt. |
Since λ∤k and λ>t>q≥2, λ is a divisor of f1, (q−1), q+1, or q, and so λ≤q+1. Since q<t<23λ, we get a contradiction. Therefore, t=1 as we claim.
Let t=1. Then, rλ=(q3−ϵ1), and k=(q3+2ϵ)2+1 with q even. If ϵ=+, then r=λ(q3−1), and k=q3+42. Since b is an integer, we get that q3+4 divides λq3(q6−1). It follows that q3+4∣60λ, and so λ divides q3+4, which is impossible as λ is a prime divisor of 2q3(q2−1)(q3−1). We now assume that ϵ=−. Then, k=q32 and b=λ(q6−1), and r=λ(q3+1) for q≥4. Moreover, in this case |TB|=f1q6(q2−1)λ and we further find that TB is contained in a maximal parabolic subgroup M=q5:GL2(q) of G2(q). Since G is flag-transitive, Lemma 2.2 implies that |SU3(q).2:Tα,B| divides λ(q3+1). Using the maximal subgroup list for SU3(q) provided in [4, Tables 8.5 and 8.6], we get that Tα,B is isomorphic to a subgroup of M1=q3:Cq2−1.2. If Tα,B=M1 or λ∤q2−1, then Tα,B contains a cyclic group of order q2−1, which contradicts Tα,B≤TB≤q5:GL2(q). Hence, |M1:Tα,B|=λ divides q2−1. This also implies that T is flag-transitive, and so |T:M||M:TB|=λ(q6−1). It follows that |M:TB|=|GL2(q):TB∩GL2(q)|=λ(q−1), which gives |TB∩GL2(q)|=q(q2−1)λ. Then, using the list of maximal subgroups of SL(2,q) provided in [4, Tables 8.1 and 8.2], we get that λ∤q−1, and so λ∣q+1, which further implies that λ=q+1. This is to say, if such design exists, then the design parameters tuple is (v,b,r,k,λ)=(q3(q3−1)2,(q+1)(q6−1),(q+1)(q3+1),q32,q+1), where λ=q+1 is a Fermat prime.
Now, we assume that q is odd. Then, we conclude that r divides λ(q3−ϵ1)2 from [17, Section 4, Case 1, i=1]. Let rt=λ(q3−ϵ1)2. Similar as in the even case, we also have t=1. That is to say, k=q3+ϵ2+1 and r=λ(q3−ϵ1)2. When ϵ=+, the fact of k dividing λq3(q6−1) q3+3 implies that q3+3 divides 24λ, and so λ divides q3+3, which is impossible as λ is a prime divisor of 2q3(q2−1)(q3−1). If ϵ=−, we have k=q3−1, and so b=λq3(q3+1)4. We consider a maximal subgroup M containing TB. It is proven later that M≅TB≅SL3(q).2 and hence that is unique. The fact that |T:M|∣b implies that M is SL3(q).2 by [4,Tables 8.41 and 8.42] and that |T:M|=q3(q3+1)2. It follows that 2|M:TB|∣λ, which forces λ=2 and M=TB≅SL3(q).2. Since Tα≅SU3(q).2 and r=q3+1, we have Tα,B≅q3.Cq2−1.2 or q3.Cq2−1. According to the maximal subgroups of SL3(q) in [4, Tables 8.3 and 8.4], we know that Tα,B is isomorphic to a subgroup of q2.GL2(q).2, which is impossible.
All other types of Gα in [1, Table 2], except two cases which we will discuss in Lemma 3.10, can be ruled out using the method stated below. First, for each possibility of Gα, the order of Gα and the value of v can be determined. We can hence get an upper bound of λ according to λ∣|Gα|. Then, to get an upper bound of r0, we consider the divisors of |Gα| in two parts: ∏i1i=1Φi for which Φi divides v, and ∏i2j=1Ψj=|Gα|/∏i1i=1Φi. Obviously, all Φi are coprime with v−1. For each Ψj, we calculate the remainder ˉΨj of Ψj divided by v−1. This implies that (|Gα|,v−1) divides |Out(T)|∏i2j=1ˉΨj, which implies that r0≤|Out(T)|∏i2j=1ˉΨj. Finally, one can check that the values of r0 for all these cases are too small to satisfy the condition that v<λr20. That is, no new designs arise in these cases. To be more explicit, we take T=E8(q) as an example.
Lemma 3.9. Assume that G and D satisfy the hypothesis of Theorem 1.1. If T=E8(q) with q=pe, then Gα cannot be a non-parabolic maximal subgroup of G.
Proof. Let T=E8(q). Then, it follows from [1, Table 2] that the type of Gα is one of the following:
{A1(q)E7(q),D8(q),E8(q12),E8(q13),Aϵ2(q)Eϵ6(q)}. |
For the case that Gα is of type A1(q)E7(q), we have λ<q8 since λ∣|Gα| and v=q56(q6+1)(q10+1)(q12+1)q30−1q2−1 by v=|G:Gα|. Obviously, q(q6+1)∣v and q30−1q2−1∣v, which also implies q6−1q2−1∣v and q10−1q2−1∣v. This means (|Gα|,v−1) divides |Out(T)|(q2−1)5(q8−1)(q14−1)(q18−1). Since r0∣(|Gα|,v−1), we have r0<q51. However, Lemma 3.2 shows q112<v<λr20<q110, a contradiction.
For the case that Gα is of type D8(q), we have λ<q7 and
v=q64(q12+q6+1)(q16+q8+1)(q10+1)(q30−1)q4−1. |
Since v−1≡2(modq4+1), (v−1,q4+1)=2 or 1. This, together with q∣v and q30−1q2−1∣v, implies that (|Gα|,v−1) divides 4|Out(T)|(q2−1)3(q4−1)3(q12−1)(q14−1). It follows that r0≤4|Out(T)|q44<4q45, and q128<v<λr20<4q97, which is a contradiction.
Assume that Gα is of type E8(q12). Then, λ≤q15 and v=q60(q+1)(q4+1)(q6+1)(q7+1)(q9+1)(q10+1)(q12+1)(q15+1). Since q, q3+1, q4+1, q5+1, and q6+1 are divisors of v, we get that (|Gα|,v−1) divides |Out(T)|(q−1)2(q3−1)2(q5−1)(q7−1)(q9−1)(q15−1). It follows that r0<q45, and so q124<v<λr20<q105, a contradiction again.
Assume that Gα is of type Aϵ2(q)Eϵ6(q) or E8(q13). Then, since Gα is non-parabolic, the Tits lemma in [18, 1.6] implies that p divides v=|G:Gα|, and so (|Gα|,v−1) is coprime with p. It follows that r0≤|Gα|p′ as r0 divides (|Gα|,v−1). This implies that v<λ|Out(T)|2|Tα|2p′ by Lemma 3.2, which cannot be satisfied when Gα is of type Aϵ2(q)Eϵ6(q) or E8(q13).
Lemma 3.10. Assume that G and D satisfy the hypothesis of Theorem 1.1. Then the type of Gα cannot be either (q−ϵ1)Dϵ5(q) when T=Eϵ6(q) or (q−ϵ1)Eϵ6(q) when T=E7(q).
Proof. Assume that T is Eϵ6(q) and Gα is of type (q−ϵ1)Dϵ5(q). Then, λ<2q4 as λ divides |Gα| and v=q16(q9−ϵ1)(q12−1)(3,q−1)(q−ϵ1)(q4−1). In addition, we know from [1, Theorem 4.1] that there exist two subdegrees: q8(q5−ϵ)(q4+1) and q10(q3+ϵ)(q8−1). Since r0 divides the greatest common divisors of every non-trivial subdegree and v−1 (Lemma 2.3), we have (r0,p)=1, and so r0∣2(q−ϵ1)(q4+1), which implies that r0 is too small to satisfy v<λr20 again.
If T is E7(q) and Gα is of type (q−ϵ1)Eϵ6(q), we have λ≤2q6 and v=q27(q5+ϵ1)(q9+ϵ1)(q14−1)q−ϵ1. [1, Theorem 4.1] shows that there exist two subdegrees, which divide q12(q5−ϵ)(q9−ϵ) and(4,qm−1ϵ)q16(q5−ϵ)(q12−1q4−1), respectively. However, by Lemma 2.3 we know that r0 is too small again.
Proof of Theorem 1.1. It follows immediately from Lemmas 3.1–3.10.
In this paper, we figure out all possible parameters of 2-(v,k,λ) designs D (with λ prime) that admit flag-transitive point-primitive automorphism groups with an exceptional Lie type socle. Our work contributes to the classification of flag-transitive 2-(v,k,λ) designs. In addition, the cases that the automorphism groups of such designs with classical socle will be the main focus in our future work.
Y. Zhang: Data curation, writing-review and editing; J. Shen: Writing-original draft. All authors have read and agreed to the published version of the manuscript.
The authors declare they have not used artificial intelligence (AI) tools in the creation of this article.
The authors would like to thank the anonymous referees for corrections and valuable comments that led to the improvement of this paper.
This work is financially supported by the National Natural Science Foundation of China (Grant number: 12301020 and 12201469) and the Science and Technology Projects in Guangzhou (Grant number: 2023A04J0027).
The authors declare no conflict of interest.
[1] |
A. Sala, R. Watson, B-Myb protein in cellular proliferation, transcription control, and cancer: Latest developments, J. Cell. Physiol., 3 (1999), 245−250. doi: 10.1002/(SICI)1097-4652(199906)179:3<245:AID-JCP1>3.0.CO;2-H. doi: 10.1002/(SICI)1097-4652(199906)179:3<245:AID-JCP1>3.0.CO;2-H
![]() |
[2] |
M. Bessa, M. Joaquin, F. Tavner, M. K. Saville, R. J. Watson, Regulation of the cell cycle by B-Myb, Blood Cells Mol. Dis., 2 (2001), 416−421. doi: 10.1006/bcmd.2001.0399. doi: 10.1006/bcmd.2001.0399
![]() |
[3] |
K. V. Tarasov, Y. S. Tarasova, W. L. Tam, D. R. Riordon, S. T. Elliott, G. Kania, et al., B-MYB is essential for normal cell cycle progression and chromosomal stability of embryonic stem cells, PloS one, 6 (2008), e2478. doi: 10.1371/journal.pone.0002478. doi: 10.1371/journal.pone.0002478
![]() |
[4] |
S. Sadasivam, J. A. DeCaprio, The DREAM complex: master coordinator of cell cycle-dependent gene expression, Nat. Rev. Cancer, 8 (2013), 585−595. doi: 10.1038/nrc3556. doi: 10.1038/nrc3556
![]() |
[5] |
M. Joaquin, R. J. Watson, Cell cycle regulation by the B-Myb transcription factor, Cell. Mol. Life Sci., 11 (2003), 2389-2401. doi: 10.1007/s00018-003-3037-4. doi: 10.1007/s00018-003-3037-4
![]() |
[6] |
S. Sadasivam, S. Duan, J. A. DeCaprio, The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression, Genes Dev., 5 (2012), 474−489. doi: 10.110r1/gad.181933.111. doi: 10.110r1/gad.181933.111
![]() |
[7] |
R. Bayley, C. Ward, P. Garcia, MYBL2 amplification in breast cancer: Molecular mechanisms and therapeutic potential, Biochim. Biophys. Acta Rev. Cancer, 2020 (2020), 188407. doi: 10.1016/j.bbcan.2020.188407. doi: 10.1016/j.bbcan.2020.188407
![]() |
[8] | F. Ren, L. Wang, X. Shen, X. Xiao, Z. Liu, P. Wei, et al., MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer, Am. J. Cancer Res., 4 (2015), 1542. |
[9] |
M. Zhang, H. Li, D. Zou, J. Gao, Ruguo key genes and tumor driving factors identification of bladder cancer based on the RNA-seq profile, Onco Targets Ther., 9 (2016), 2717. doi: 10.2147/ott.s92529. doi: 10.2147/ott.s92529
![]() |
[10] |
Z. Guan, W. Cheng, D. Huang, A. Wei, High MYBL2 expression and transcription regulatory activity is associated with poor overall survival in patients with hepatocellular carcinoma, Curr. Res. Transl. Med., 1 (2018), 27−32. doi: 10.1016/j.retram.2017.11.002. doi: 10.1016/j.retram.2017.11.002
![]() |
[11] | G. Raschellà, V. Cesi, R. Amendola, A. Negroni, B. Tanno, P. Altavista, et al., Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification, Cancer Res., 14 (1999), 3365−3368. |
[12] |
O. Fuster, M. Llop, S. Dolz, P. Garcíab, E. Suchc, M. Ibáñez, et al., Adverse prognostic value of MYBL2 overexpression and association with microRNA-30 family in acute myeloid leukemia patients, Leuk. Res., 12 (2013), 1690−1696. doi: 10.1016/j.leukres.2013.09.015. doi: 10.1016/j.leukres.2013.09.015
![]() |
[13] |
S. A. Forbes, D. Beare, P. Gunasekaran, K. Leung, N. Bindal, H. Boutselakis, et al., COSMIC: exploring the world's knowledge of somatic mutations in human cancer, Nucleic Acids Res., D1 (2015), D805−D811. doi: 10.1093/nar/gku1075. doi: 10.1093/nar/gku1075
![]() |
[14] |
D. R. Rhodes, S. Kalyana-Sundaram, V. Mahavisno, R. Varambally, J. Yu, B. B. Briggs, et al., Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles, Neoplasia, 2 (2007), 166−180. doi: 10.1593/neo.07112. doi: 10.1593/neo.07112
![]() |
[15] |
J. Vivian, A. A. Rao, F. A. Nothaft, C. Ketchum, J. Armstrong, A. Novak, et al., Toil enables reproducible, open source, big biomedical data analyses, Nat. Biotechnol., 4 (2017), 314−316. doi: 10.1038/nbt.3772. doi: 10.1038/nbt.3772
![]() |
[16] |
J. Gao, B. A. Aksoy, U. G. Dogrusoz, Dresdner, B. Gross, S. O. Sumer, et al., Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal, Sci. Signal., 269 (2013), pl1−pl1. doi: 10.1126/scisignal.2004088. doi: 10.1126/scisignal.2004088
![]() |
[17] |
E. Cerami, J. Gao, U. Dogrusoz, B. E. Gross, S. O. Sumer, B. A. Aksoy, et al., The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data, Cancer Discov, 2 (2012). doi: 10.1158/2159-8290.CD-12-0095. doi: 10.1158/2159-8290.CD-12-0095
![]() |
[18] |
H. Mizuno, K. Kitada, K. Nakai, A. Sarai, PrognoScan: a new database for meta-analysis of the prognostic value of genes, BMC Med. Genomics, 1 (2009), 1−11. doi: 10.1186/1755-8794-2-18. doi: 10.1186/1755-8794-2-18
![]() |
[19] |
B. Györffy, A. Lanczky, A. C. Eklund, C. Denkert, J. Budczies, Q. Li, et al., An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients, Breast Cancer Res. Treat., 3 (2010), 725−731. doi: 10.1007/s10549-009-0674-9. doi: 10.1007/s10549-009-0674-9
![]() |
[20] |
S, R. Falcon, R. Gentleman, Using GOstats to test gene lists for GO term association, Bioinformatics, 2 (2007), 257−258. doi: 10.1093/bioinformatics/btl567. doi: 10.1093/bioinformatics/btl567
![]() |
[21] |
H. Hu, Y. R. Miao, L. H. Jia, Q. Y. Yu, Q. Zhang, A. Y. Guo, et al., AnimalTFDB 3.0: a comprehensive resource for annotation and prediction of animal transcription factors, Nucleic Acids Res., D1 (2019), D33−D38. doi: 10.1093/nar/gky822. doi: 10.1093/nar/gky822
![]() |
[22] | P. Shannon, M. Richards, An annotated collection of protein-DNA binding sequence motifs, 2021. Available from: https://xueshu.baidu.com/usercenter/paper/show?paperid=73fac988c60c44137363f1c554acbdea. |
[23] |
H. Pagès, P. Aboyoun, R. Gentleman, S. DebRoy, Biostrings: Efficient manipulation of biological strings, Bioconductor, 2021 (2021). doi: 10.18129/B9.bioc.Biostrings. doi: 10.18129/B9.bioc.Biostrings
![]() |
[24] |
F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, A. Jema, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J. Clin., 6 (2018), 394−424. doi: 10.3322/caac.21492. doi: 10.3322/caac.21492
![]() |
[25] |
R. Zheng, C. Wan, S. Mei, Q. Qin, Q. Wu, H. Sun, et al., Cistrome Data Browser: expanded datasets and new tools for gene regulatory analysis, Nucleic Acids Res., D1 (2019), D729−D735. doi: 10.1093/nar/gky1094. doi: 10.1093/nar/gky1094
![]() |
[26] |
H. Nord, U. Segersten, J. Sandgren, K. Wester, C. Busch, U. Menzel, et al., Focal amplifications are associated with high grade and recurrences in stage Ta bladder carcinoma, Int. J. Cancer, 6 (2010), 1390−1402. doi: 10.1002/ijc.24954. doi: 10.1002/ijc.24954
![]() |
[27] |
K. Inoue, E. A. Fry, Novel molecular markers for breast cancer, Biomark. Cancer, 8 (2016), S38394. doi: 10.4137/BIC.S38394. doi: 10.4137/BIC.S38394
![]() |
[28] | F. Ren, L. Wang, X. Shen, X. Xiao, Z. Liu, P. Wei, et al., MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer, Am. J. Cancer Res., 4 (2015), 1542. |
[29] |
H. D. Qin, X. Y. Liao, Y. B. Chen, S. Yi. Huang, W. Q. Xue, F. F. Li, et al., Genomic characterization of esophageal squamous cell carcinoma reveals critical genes underlying tumorigenesis and poor prognosis, Am. J. Hum. Genet., 4 (2016), 709−727. doi: 10.1016/j.ajhg.2016.02.021. doi: 10.1016/j.ajhg.2016.02.021
![]() |
[30] |
J. Musa, M. M. Aynaud, O. Mirabeau, O. Delattre, T. G. Grünewald, MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis, Cell Death Dis., 6 (2017), e2895−e2895. doi: 10.1038/cddis.2017.244. doi: 10.1038/cddis.2017.244
![]() |
[31] |
M. Fischer, M. Quaas, L. Steiner, The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes, Nucleic Acids Res., 1 (2016), 164−174. doi: 10.1093/nar/gkv927. doi: 10.1093/nar/gkv927
![]() |
[32] |
Bioconductor package maintainer, Finding candidate binding sites for known transcription factors via sequence matching, Bioconductor, 2018 (2018). doi: 10.18129/B9.bioc.generegulation. doi: 10.18129/B9.bioc.generegulation
![]() |
[33] |
X. Zhao, X. Li, Z. Ma, M. H. Yin, Identify DNA-binding proteins with optimal Chou's amino acid composition, Protein Pept. Lett., 4 (2012), 398−405. doi: 10.2174/092986612799789404. doi: 10.2174/092986612799789404
![]() |
[34] |
Y. Wang, Z. Ma, K. C. Wong, X. Li, Nature-inspired multiobjective patient stratification from cancer gene expression data, Inf. Sci., 526 (2020), 245−262. doi: 10.1016/j.ins.2020.03.095. doi: 10.1016/j.ins.2020.03.095
![]() |
[35] |
Y. Wang, B. Liu, Z. Ma, K. C. Wong, X. Li, Nature-inspired multiobjective cancer subtype diagnosis, IEEE J. Transl. Eng. Health Med., 7 (2019), 1−12. doi: 10.1109/jtehm.2019.2891746. doi: 10.1109/jtehm.2019.2891746
![]() |
[36] |
Y. Wang, Z. Ma, K. C. Wong, X. Li, Evolving multiobjective cancer subtype diagnosis from cancer gene expression data, IEEE/ACM Trans. Comput. Biol. Bioinform., 6 (2020), 2431−2444. doi: 10.1109/tcbb.2020.2974953. doi: 10.1109/tcbb.2020.2974953
![]() |
![]() |
![]() |
1. | Dingmi Sun, Yimin Chen, Hao Li, Intelligent Vehicle Computation Offloading in Vehicular Ad Hoc Networks: A Multi-Agent LSTM Approach with Deep Reinforcement Learning, 2024, 12, 2227-7390, 424, 10.3390/math12030424 |