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Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

The Prognostic and Clinicopathologic Characteristics of OCT4 and Lung Cancer: A Meta-Analysis

Author(s): Hui Li*, Liwen Wang, Shupeng Shi, Yadong Xu, Xuejiao Dai, Hongru Li, Jing Wang, Qiong Zhang, Yonggang Wang, Shuming Sun* and Yanping Li*

Volume 19 , Issue 1 , 2019

Page: [54 - 75] Pages: 22

DOI: 10.2174/1566524019666190308163315

Price: $65


Objective: The relationship between OCT4 and clinicopathological features in lung cancer is shown to be controversial in recent publications. Therefore, we conducted this meta-analysis to quantitatively investigate the prognostic and clinicopathological characteristics of OCT4 in lung cancer.

Methods: A comprehensive literature search of the PubMed, EMBASE, Cochrane Library, WOS, CNKI and Wanfang databases was performed to identify studies. Correlations between OCT4 expression and survival outcomes or clinicopathological features were analyzed using meta-analysis methods.

Results: Twenty-one studies with 2523 patients were included. High OCT4 expression showed a poorer overall survival (OS) (univariate: HR= 2.00, 95% CI = (1.68, 2.39), p<0.0001; multivariate: HR= 2.43, 95% CI = (1.67, 3.55), p<0.0001) and median overall survival (MSR = 0.51, 95% CI = (0.44, 0.58), p < 0.0001), disease-free survival (DFS) (HR= 2.18, 95% CI = (1.30, 3.67), p = 0.003) and poorer disease-specific survival (DSS) (HR= 2.23, 95% CI = (1.21, 4.11), p = 0.010). Furthermore, high OCT4 expression was found to be related with lower 5 year disease-specific survival rate (OR= 0.24, 95% CI = (0.14, 0.41), p<0.0001) and 10 year overall survival rate (OR= 0.22, 95% CI = (0.12, 0.40), p=0.0001). Additionally, OCT4-high expression was also strongly associated with higher clinical TNM stage, lymph node metastasis, tumor distant metastasis, higher histopathologic grade, but not related with gender, smoking status, tumor size and histologic type of lung cancer.

Conclusion: OCT4 over-expression in lung cancer was strongly related to poorer clinicopathological features and worse survival outcomes, which suggests that OCT4 could be a valuable prognostic marker in lung cancer.

Keywords: OCT4, lung cancer, meta-analysis, clinicopathological characteristics, prognosis, marker.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics 2016. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2016; 66: 271-89.
Ilie M, Benzaquen J, Hofman V, et al. Immunotherapy in non-small cell lung cancer: Biological principles and future opportunities. Curr Mol Med 2017; 17: 527-40.
Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med 2006; 355: 1253-61.
Mimeault M, Hauke R, Mehta PP, Batra SK. Recent advances in cancer stem/progenitor cell research: Therapeutic implications for overcoming resistance to the most aggressive cancers. J Cell Mol Med 2007; 11: 981-1011.
Ponti D, Costa A, Zaffaroni N, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005; 65: 5506-11.
Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007; 67: 1030-7.
Eramo A, Lotti F, Sette G, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 2008; 15: 504.
Chen WJ, Ho CC, Chang YL, et al. Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling. Nat Commun 2014; 5: 3472.
Lu Y, Futtner C, Rock JR, et al. Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One 2010; 5: e11022.
Chiou SH, Wang ML, Chou YT, et al. Coexpression of oct4 and nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell–like properties and epithelial–mesenchymal transdifferentiation. Cancer Res 2010; 70: 10433-44.
Chen YC, Hsu HS, Chen YW, et al. Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One 2008; 3: e2637.
Zhang X, Wang H, Jin B, Dong Q, Huang J, Han B. Correlations between OCT4 expression and clinicopathological factors and prognosis of patients with lung adenocarcinoma. Zhongguo fei ai za zhi Chinese journal of lung cancer 2013; 16: 197-202.
Hadi NI, Jamal Q. “OMIC” tumor markers for breast cancer: A review. Pak J Med Sci 2015; 31: 1256.
Li H, Wu D, Shi S, et al. Expression and clinical significance of CD147 in renal cell carcinoma: A meta-analysis. Oncotarget 2017; 8: 51331.
Li H, Jiang C, Wu D, et al. The prognostic and clinicopathologic characteristics of CD147 and esophagus cancer: A meta-analysis. PLoS One 2017; 12: e0180271.
Díez M, Torres A, Maestro ML, et al. Prediction of survival and recurrence by serum and cytosolic levels of CEA, CA125 and SCC antigens in resectable non-small-cell lung cancer. Br J Cancer 1996; 73: 1248.
Liu W, Yuan W, Li X, et al. ZNF424 induces apoptosis and inhibits proliferation in lung carcinoma cells. Curr Mol Med 2018; 18: 109-15.
Ryan AK, Rosenfeld MG. POU domain family values: Flexibility, partnerships, and developmental codes. Genes Dev 1997; 11: 1207-25.
Li XL, Jia LL, Shi MM, et al. Downregulation of KPNA2 in non-small-cell lung cancer is associated with Oct4 expression. J Transl Med 2013; 11: 232.
Tang YA, Chen CH, Sun HS, et al. Global Oct4 target gene analysis reveals novel downstream PTEN and TNC genes required for drug-resistance and metastasis in lung cancer. Nucleic Acids Res 2015; 43: 1593-608.
Xu C, Xie D, Yu SC, et al. β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma. Cancer Res 2013; 73: 3181-9.
Lin YH, Zhang LL, Liu CG. Co-expression of Oct-4 and Nestin in human lung cancer. China Medical Herald 2013; 20: 4-6.
Li PH, Lv HN, Han LB. Expression and clinical significance of Oct4 and Sox2 in human lung cancer. handong Medical Journal 2012; 20: 79-81.
Rodriguez E, Chen L, Ao MH, et al. Expression of transcript factors SALL4 and OCT4 in a subset of non-small cell lung carcinomas (NSCLC). Translational respiratory medicine 2014; 2: 10.
Wells G, Shea B, O’Connell D, et al. The Newcastle–Ottawa Scale (NOS) for Assessing the Quality of Non-Randomized Studies in Meta-Analysis. Ottawa Hospital Research Institute 2000.
Li H, Xu Y, Li H. CD147 as a novel biomarker for predicting the prognosis and clinicopathological features of bladder cancer: A meta-analysis. Oncotarget 2017; 8: 62573.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8: 16.
Duval S, Tweedie R. Trim and fill: A simple funnel‐plot–based method of testing and adjusting for publication bias in meta‐analysis. Biometrics 2000; 56: 455-63.
Calabuig S, Jantus-Lewintre E, Lucas R, et al. Tumor expression levels of CSC markers in resectable non-small cell lung cancer. J Clin Res Oncol 2014; 32: 7562.
Chen SF, Lin YS, Jao SW, et al. Pulmonary adenocarcinoma in malignant pleural effusion enriches cancer stem cell properties during metastatic cascade. PLoS One 2013; 8: e54659.
Chiou GY, Cherng JY, Hsu HS, et al. Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial–mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma. J Control Release 2012; 159: 240-50.
Cortes-Dericks L, Galetta D, Spaggiari L, Schmid RA, Karoubi G. High expression of octamer-binding transcription factor 4A, prominin-1 and aldehyde dehydrogenase strongly indicates involvement in the initiation of lung adenocarcinoma resulting in shorter disease-free intervals. Eur J Cardiothorac Surg 2012; 41: e173-81.
Jen J, Tang YA, Lu YH, Lin CC, Lai WW, Wang YC. Oct4 transcriptionally regulates the expression of long non-coding RNAs NEAT1 and MALAT1 to promote lung cancer progression. Mol Cancer 2017; 16: 104.
Park E, Park SY, Sun PL, et al. Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma. Oncotarget 2016; 7: 42502.
Kim TJ, Lee YS, Lee KY, Kang CS. Clinical implication of oct4 expression in squamous cell carcinoma of lung. Korean J Pathol 2010; 44: 631-5.
Li B. Expression and molecular mechanism of Oct4 in the resistance of non-small cell lung cancer to gefitinib. PhD Thesis Jinan: Shandong University May 2017.
Li X, Wang J, Xu Z, et al. Expression of sox2 and oct4 and their clinical significance in human non-small-cell lung cancer. Int J Mol Sci 2012; 13: 7663-75.
Liu H. Expression of Oct4 and its clinical significance in human non-small-cell lung cancer. Journal of Luzhou Medical College 2012; 01: 51.
Liu X, Ma M, Duan X, Zhang H, Yang M. Knockdown of OCT4 may sensitize NSCLC cells to cisplatin. Clin Transl Oncol 2017; 19: 587-92.
Maierdan S, Alidan E, Jin Z, Tiehan HE. Human lung adenocarcinoma stem cell phenotypes and patient’s prognosis. Chinese Journal of Tissue Engineering Research 2015; 19: 1523-7.
Requena R, Lewintre EJ, Lucas R, et al. Expression of stemness factors OCT4and NANOG in resectable non-small cell lung cancer. J Thorac Oncol 2013; 8: 1090-1.
Su C, Li X, Zhou C, et al. Stem cell transcription factors Oct4 and Nanog involved in chemoresistance and EGFR-TKI resistance of NSCLC. J Thorac Oncol 2013; 8: 770.
Wei L, Liu X, Hu C. Correlation between expression of HIF- 2α and OCT-4 and prognosis of NSCLC. Zhong nan da xue xue bao. Yi xue ban Journal of Central South University Medical sciences 2011 Sep; 36: 854-8.
Xiang BL, Li LL, Cao L, et al. Correlation between the expression of transcription factor Oct4 and Sox2 and the pathological grades and clinical stages in lung cancer. Journal of Hunan Normal University (Medical Sciences), 2016; 01: 95-7.
Xin YH, Yang XJ, Cui W, et al. POU5F1 enhances the invasiveness of cancer stem-like cells in lung adenocarcinoma by upregulation of MMP-2 expression. PLoS One 2013; 8: e83373.
Lewiński T, Żuławski M. Small cell lung cancer survival: 3 years as a minimum for predicting a favorable outcome. Lung Cancer 2003; 40: 203-13.
Garfield DH, Franklin WA. A comparison of survival and disease‐specific survival in surgically resected, lymph node‐positive bronchioloalveolar carcinoma versus nonsmall cell lung cancer: Implications for adjuvant therapy. Cancer 2008; 113: 1107-8.
Goldstraw P, Crowley J, Chansky K, et al. International association for the study of lung cancer international staging committee. The IASLC lung cancer staging project: Proposals for the revision of the tnm stage groupings in the forthcoming (seventh) edition of the tnm classification of malignant tumours. J Thorac Oncol 2007; 2: 706-14.
Lee BE, Port JL, Stiles BM, et al. TNM stage is the most important determinant of survival in metachronous lung cancer. Ann Thorac Surg 2009; 88: 1100-5.
Marquette D, Pichon E, Deschasse G, et al. Lung cancer in adults: Better prognosis of patients aged 45 and under related to good condition and lower TNM stage (a comparative and retrospective study). Presse Med (Paris, France: 1983) 2012; 41: e250-6.
Rami-Porta R, Bolejack V, Crowley J, et al. The IASLC lung cancer staging project: Proposals for the revisions of the T descriptors in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol 2015; 10: 990- 1003.
Tang W, Wu N, Ouyang H, et al. Preoperative T stage of non-small cell lung cancer: Comparison of the efficacy of 64-MDCT versus 3.0 T MR imaging. Zhonghua Zhong Liu Za Zhi [Chinese journal of oncology] 2015; 37: 617-21.
Asamura H, Chansky K, Crowley J, et al. The international association for the study of lung cancer lung cancer staging project: Proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol 2015; 10: 1675-84.
Postmus PE, Brambilla E, Chansky K, et al. The IASLC Lung Cancer Staging Project: Proposals for revision of the M descriptors in the forthcoming (seventh) edition of the TNM classification of lung cancer. J Thorac Oncol 2007; 2: 686-93.
Sun Z, Aubry MC, Deschamps C, et al. Histologic grade is an independent prognostic factor for survival in non–small cell lung cancer: An analysis of 5018 hospital-and 712 population-based cases. J Thorac Cardiovasc Surg 2006; 131: 1014-20.
Itaya T, Yamaoto N, Ando M, et al. Influence of histological type, smoking history and chemotherapy on survival after first‐line therapy in patients with advanced non‐small cell lung cancer. Cancer Sci 2007; 98: 226-30.
Johnson P. Role of alpha‐fetoprotein in the diagnosis and management of hepatocellular carcinoma. J Gastroenterol Hepatol 1999; 14: S32-6.
Wagener C, Müller-Wallraf R, Nisson S, Gröner J, Breuer H. Localization and concentration of carcinoembryonic antigen (CEA) in gastrointestinal tumors: Correlation with CEA levels in plasma. J Natl Cancer Inst 1981; 67: 539-47.
Li H. Xi Z2, Dai X. CD147 and glioma: A meta-analysis. J Neurooncol 2017; 134: 145-56.
Sethi S, Ali S, Philip P, Sarkar F. Clinical advances in molecular biomarkers for cancer diagnosis and therapy. Int J Mol Sci 2013; 14: 14771-84.
Liang Y, Zhuo Y, Lin Z, et al. Decreased expression of MYPT1 contributes to tumor angiogenesis and poor patient prognosis in human prostate cancer. Curr Mol Med 2018; 18: 100-8.
Karia BT, Zamuner FT, Carlin V, de Oliveira CZ, Carvalho AL, Vettore AL. Expression and prognostic relevance of GAGE1 and XAGE1 cancer/testis antigens in head and neck squamous cell carcinoma. Curr Mol Med 2017; 17: 707-17.
Bozorg-Ghalati F, Hedayati M. Molecular biomarkers of anaplastic thyroid carcinoma. Curr Mol Med 2017; 17: 181-8.
Boiani M, Schöler HR. Developmental cell biology: Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol 2005; 6: 872.
Nichols J, Zevnik B, Anastassiadis K, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 1998; 95: 379-91.
Liang J, Wan M, Zhang Y, et al. Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nat Cell Biol 2008; 10: 731-9.
Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 2003; 113: 643-55.
Ling TY, Kuo MD, Li CL, et al. Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro. Proc Natl Acad Sci 2006; 103: 9530-5.

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