Research article

Expression of autophagy-related factor p62 for lung cancer diagnosis and prognosis: A systematic review and meta-analysis

  • Received: 20 February 2019 Accepted: 10 July 2019 Published: 26 July 2019
  • p62/SQSTM1 is the scaffold protein implicated in selective autophagy, which is induced by cellular stress. Research has shown that p62 is highly expressed in cancer. Moreover, p62 can easily promote tumor metastasis. However, studies have not reached a consensus on the relationship of p62 expression with the diagnosis and prognosis of lung cancer. We conducted a systematic review and meta-analysis of studies on p62 expression in the prognosis and clinical-pathological parameters of lung cancer patients. Literature search was performed with PubMed, Web of Science, EMBASE, Cochrane Library, and SpringerLink databases. Fixed-effects and random-effects models were used to study the relationship of p62 expression with patients' overall survival (OS) and clinical-pathological parameters. I2 was used to test for heterogeneity. Egger's test was used to assess publication bias. The meta-analysis collected and considered 13 articles, which included 1393 lung cancer patients. The studies show that the high expression of p62 is associated with poor OS in lung cancer patients. The clinical-pathological parameters of patients show that p62 is more highly expressed in high TNM stage (Ⅱ + Ⅲ + Ⅳ VS. Ⅰ), Lymph node metastasis (N1 VS. N0), and distant metastases (D1 VS. D0). However, there is no correlation between the p62 expression and the Beclin 1 and LC3B in lung cancer patients. In conclusion, the over-expression of p62 is associated with poor OS in lung cancer patients and can be used as a biomarker for lung cancer diagnosis and prognosis.

    Citation: Bijiong Wang, Yaodong Tang, Biyun Yu, Di Gui, Hui Xu. Expression of autophagy-related factor p62 for lung cancer diagnosis and prognosis: A systematic review and meta-analysis[J]. Mathematical Biosciences and Engineering, 2019, 16(6): 6805-6821. doi: 10.3934/mbe.2019340

    Related Papers:

  • p62/SQSTM1 is the scaffold protein implicated in selective autophagy, which is induced by cellular stress. Research has shown that p62 is highly expressed in cancer. Moreover, p62 can easily promote tumor metastasis. However, studies have not reached a consensus on the relationship of p62 expression with the diagnosis and prognosis of lung cancer. We conducted a systematic review and meta-analysis of studies on p62 expression in the prognosis and clinical-pathological parameters of lung cancer patients. Literature search was performed with PubMed, Web of Science, EMBASE, Cochrane Library, and SpringerLink databases. Fixed-effects and random-effects models were used to study the relationship of p62 expression with patients' overall survival (OS) and clinical-pathological parameters. I2 was used to test for heterogeneity. Egger's test was used to assess publication bias. The meta-analysis collected and considered 13 articles, which included 1393 lung cancer patients. The studies show that the high expression of p62 is associated with poor OS in lung cancer patients. The clinical-pathological parameters of patients show that p62 is more highly expressed in high TNM stage (Ⅱ + Ⅲ + Ⅳ VS. Ⅰ), Lymph node metastasis (N1 VS. N0), and distant metastases (D1 VS. D0). However, there is no correlation between the p62 expression and the Beclin 1 and LC3B in lung cancer patients. In conclusion, the over-expression of p62 is associated with poor OS in lung cancer patients and can be used as a biomarker for lung cancer diagnosis and prognosis.


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    [1] S. Huq, I. Maghfoor, M. Perry, et al., Lung Cancer, Ann. Saudi Med., 25 (2005), 1–12.
    [2] B. Piperdi, A. Merla and R. Perez-Soler, Targeting angiogenesis in squamous non-small cell lung cancer, Drugs, 74 (2014), 403–413.
    [3] A. J. Alberg, M. V. Brock, J. G. Ford, et al., Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines, Chest, 143 (2013), e369S–399S.
    [4] D. Inoue, T. Suzuki, Y. Mitsuishi, et al., Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma, Cancer Sci., 103 (2012), 760–766.
    [5] G. L. Jin, H. S. Ju, H. S. Shim, et al., Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions, Resp. Res., 16 (2015), 1–9.
    [6] X. Li and Z. Fan, The epidermal growth factor receptor antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1alpha and Bcl-2 and activating the beclin 1/hVps34 complex, Cancer Res., 70 (2010), 5942–5952.
    [7] L. Galluzzi, F. Pietrocola, J. M. Bravo-San Pedro, et al., Autophagy in malignant transformation and cancer progression, Embo. J., 34 (2015), 856–880.
    [8] A. Puissant, N. Fenouille and P. Auberger, When autophagy meets cancer through p62/SQSTM1, Am. J. Cancer Res., 2 (2012), 397.
    [9] J. Moscat and M. T. Diazmeco, p62: A versatile multitasker takes on cancer, Trends Biochem. Sci., 37 (2012), 230–236.
    [10] P. Shi, S. Wang, J. Zhang, et al., Effect of all- trans -retinoic acid on mRNA binding protein p62 in human gastric cancer cells, Int. J. Biochem. Cell B, 37 (2005), 616–627.
    [11] R. Z. Luo, Z. Y. Yuan, M. Li, et al., Accumulation of p62 is associated with poor prognosis in patients with triple-negative breast cancer, Oncotargets Ther., 6 (2013), 883–888.
    [12] W. Chen, R. Zheng, H. Zeng, et al., Epidemiology of lung cancer in China, Thorac. Cancer, 6 (2015), 209–215.
    [13] R. A. Ellis, S. Horswell, T. Ness, et al., Prognostic impact of p62 expression in cutaneous malignant melanoma, J. Invest. Dermatol., 134 (2013), 1476–1478.
    [14] K. Xu, Z. Chen, L. Zhou, et al., Clinical significance of expression of autophagyrelated proteins Beclin1, LC3 and P62 in advanced pancreatic cancer, Acta Geol. Sin., 23 (2012).
    [15] R. Feng, G. Shu, G. Liu, et al., Knockdown of p62/sequestosome 1 attenuates autophagy and inhibits colorectal cancer cell growth, Mol. Cell. Biochem., 385 (2014), 95–102.
    [16] A. Belaid, P. D. Ndiaye, M. Cerezo, et al., Autophagy and SQSTM1 on the RHOA(d) again, Autophagy., (2014), 201–208.
    [17] I. Tamir, J. C. Stolpa, C. D. Helgason, et al., The RasGAP-Binding Protein p62 dok Is a Mediator of Inhibitory FcγRIIB Signals in B Cells, Immunity, 12 (2000), 347–358.
    [18] J. H. Kim, S. K. Hong, P. K. Wu, et al., Raf/MEK/ERK can regulate cellular levels of LC3B and SQSTM1/p62 at expression levels, Exp. Cell. Res., 327 (2014), 340–352.
    [19] A. D. Cristofano, M. Niki, M. Zhao, et al., P62, a negative regulator of ras and mitogen-activated protein kinase (Mapk) activity, opposes leukemogenesis by P210, J. Exp. Med., 194 (2001), 275–284.
    [20] J. Long, T. P. Garner, M. J. Pandya, et al., Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-kappaB signalling, J. Mol. Biol., 396 (2010), 178–194.
    [21] J. A. Koziol, J. Y. Zhang, C. A. Casiano, et al., Recursive partitioning as an approach to selection of immune markers for tumor diagnosis, Clin. Cancer. Res., 9 (2003), 5120–5126.
    [22] W. N. Rom, J. D. Goldberg, D. Addrizzoharris, et al., Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers, BMC Cancer, 10 (2010), 3163–3172.
    [23] X. Wang, Z. Du, L. Li, et al., Beclin 1 and p62 expression in non-small cell lung cancer: relation with malignant behaviors and clinical outcome, Int. J. Clin. Exp. Patho., 8 (2015), 10644–10652.
    [24] A. M. Schläfli , O. Adams , J. A. Galván, et al., Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer, Oncotarget, 7 (2016).
    [25] A. M. Schläfli , S. Berezowska , O. Adams, et al., Reliable LC3 and p62 autophagy marker detection in formalin fixed paraffin embedded human tissue by immunohistochemistry, Eur. J. Histochem., 59 (2014).
    [26] L. Rupert, N. Christina, K. Manuel, et al., Expression analysis of autophagy related markers LC3B, p62 and HMGB1 indicate an autophagy-independent negative prognostic impact of high p62 expression in pulmonary squamous cell carcinomas, Cancers, 9 ( 2018) Aug 21; 10.
    [27] Y. Chen, I. Petersen, B. Theis, et al., The clinical influence of autophagy-associated proteins on human lung cancer, Dis. Markers,2018,(2018-1-9), 2018 (2018), 1–9.
    [28] C. Wang, Y. Li, Y. Li, et al., Expression and clinical significance of lc-3 and p62 in non-small cell lung cancer, Chin. J. Cancer, 21 (2018), 445
    [29] J. J. Qi, X. F. Han, X. L. Cai, et al., Expression and clinical significance of autophagy-related gene Beclin1 and P62 in nasal polyps, Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi., 51 (2016), 428–432.
    [30] S. Yang, L. Z. Liang, M. H. Hong, et al., Expression and clinical significance of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 in epithelial ovarian cancer, Chin. J. Cancer, 27 (2008), 595–599.
    [31] X. Wang, Z. Du, L. Li, et al., Beclin 1 and p62 expression in non-small cell lung cancer: Relation with malignant behaviors and clinical outcome, Int. J. Clin. Exp. Pathol., 8 (2015), 10644–10652.
    [32] H. M. Wu, L. J. Shao, Z. F. Jiang, et al., Gemcitabine-induced autophagy protects human lung cancer cells from apoptotic death, Lung, (2016), 1–8.
    [33] J. Y. Guo and E. White, Autophagy is required for mitochondrial function, lipid metabolism, growth, and fate of KRASG12D-driven lung tumors, Autophagy, 9 (2013), 1636–1638.
    [34] H. Huang, J. Zhu, L. Yang, et al., Upregulation of SQSTM1/p62 contributes to nickel-induced malignant transformation of human bronchial epithelial cells, Autophagy, 12 (2016), 1687–1703.
    [35] R. X. Zeng, Y. B. Zhang, Y. Fan, et al., p62/SQSTM1 is involved in caspase-8 associated cell death induced by proteasome inhibitor MG132 in U87MG cells, Cell. Biol. Int., 38 (2014), 1221–1226.
    [36] E. Shvets and Z. Elazar, Autophagy-independent incorporation of GFP-LC3 into protein aggregates is dependent on its interaction with p62/SQSTM1, Autophagy, 4 (2008), 1054–1056.
    [37] I. Dikic, T. Johansen and V. Kirkin, Selective autophagy in cancer development and therapy, Cancer Res., 70 (2010), 3431–3434.
    [38] J. M. Norman, G. M. Cohen and E. T. Bampton, The in vitro cleavage of the hAtg proteins by cell death proteases, Autophagy, 6 (2010), 1042–1056.
    [39] Z. Jin, Y. Li, R. Pitti, et al., Cullin3-based polyubiquitination and p62-dependent aggregation of Caspase-8 mediate extrinsic apoptosis signaling, Cell, 137 (2009), 672–684.
    [40] J. Moscat and M. T. Diaz-Meco, p62 at the crossroads of autophagy, apoptosis, and cancer, Cell, 137 (2009), 1001.
    [41] R. Mathew, C. M. Karp, B. Beaudoin, et al., Autophagy suppresses tumorigenesis through elimination of p62, Cell, 137 (2009), 1062–1075.
    [42] W. Liu, B. Peng, Y. Lu, et al., Autoantibodies to tumor-associated antigens as biomarkers in cancer immunodiagnosis, Autoimmun. Rev., 10 (2011), 331–335.
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