Expression of Sox2 and Oct4 and Their Clinical Significance in Human Non-Small-Cell Lung Cancer

Sox2 and Oct4 are transcription factors with the characteristics of regulating self-renewal and differentiation of embryonic stem cell. The aim of this study was to detect the expression of Sox2 and Oct4 and analyze their clinical significance in human non-small-cell lung cancer (NSCLC). Expression of Sox2 and Oct4 were assayed in cancer tissues and their corresponding paracancerous tissues from 44 patients with NSCLC and 21 patients with benign tumors using immunohistochemistry, Western blot, reverse transcription polymerase chain reaction (RT-PCR). The correlation between the expression of Sox2 and Oct4 and tumor type, grade and prognosis and the utility of the two genes in discriminating between benign and malignant tumors were analyzed as well. The results showed that Sox2 and Oct4 positive staining was only seen in the nuclei of cancer cells but not in either the precancerous tissues or benign tumor tissues by immunohistochemistry (p < 0.01). Furthermore, in the lung cancer tissue, the positive rate for Sox2 and Oct4 was 70.5% and 54.5%, respectively. Meanwhile, clinicopathological correlations showed that the Oct4 expression level was significantly associated with poorer differentiation and higher TNM stage of the cancer (p < 0.05). Western blot and RT-PCR analysis showed similar results to immunohistochemistry. Follow-up analysis revealed that expression of Oct4 was significantly associated with poor prognosis of lung cancer. The conclusion is that Sox2 and Oct4 may act as the promising unit markers in directing NSCLC diagnosis and therapy. Also, Oct4 can be regarded as a novel predictor of poor prognosis for NSCLC patients undergoing resection.

[1]  F. Wang,et al.  Octamer 4 Small Interfering RNA Results in Cancer Stem Cell-Like Cell Apoptosis , 2012 .

[2]  Masashi Toyoda,et al.  Possible linkages between the inner and outer cellular states of human induced pluripotent stem cells , 2011, BMC Systems Biology.

[3]  Weihua Jia,et al.  Role of Sox2 and Oct4 in predicting survival of hepatocellular carcinoma patients after hepatectomy. , 2011, Clinical biochemistry.

[4]  A. Jemal,et al.  Cancer Statistics, 2010 , 2010, CA: a cancer journal for clinicians.

[5]  N. Nakatsuji,et al.  Role of SOX2 in maintaining pluripotency of human embryonic stem cells , 2010, Genes to cells : devoted to molecular & cellular mechanisms.

[6]  T. Hussenet,et al.  SOX2 in squamous cell carcinoma: Amplifying a pleiotropic oncogene along carcinogenesis , 2010, Cell cycle.

[7]  E. Brambilla,et al.  SOX2 Is an Oncogene Activated by Recurrent 3q26.3 Amplifications in Human Lung Squamous Cell Carcinomas , 2010, PloS one.

[8]  Changdong Lu,et al.  Oct3/4 and Sox2 are significantly associated with an unfavorable clinical outcome in human esophageal squamous cell carcinoma. , 2009, Anticancer research.

[9]  Paolo Malatesta,et al.  SOX2 Silencing in Glioblastoma Tumor‐Initiating Cells Causes Stop of Proliferation and Loss of Tumorigenicity , 2009, Stem cells.

[10]  J. McNamara Cancer Stem Cells , 2007, Methods in Molecular Biology.

[11]  J. Reis-Filho,et al.  Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer , 2007, Modern Pathology.

[12]  A. Stoffel,et al.  Squamous cell carcinoma related oncogene/DCUN1D1 is highly conserved and activated by amplification in squamous cell carcinomas. , 2006, Cancer research.

[13]  Y. Tsutani,et al.  Histopathologic Evaluation of Stepwise Progression of Pancreatic Carcinoma with Immunohistochemical Analysis of Gastric Epithelial Transcription Factor SOX2: Comparison of Expression Patterns between Invasive Components and Cancerous or Nonneoplastic Intraductal Components , 2006, Pancreas.

[14]  Megan F. Cole,et al.  Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells , 2005, Cell.

[15]  T. Jacks,et al.  Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer , 2005, Cell.

[16]  C. Esposito,et al.  Early diagnosis of lung cancer by detection of tumor liberated protein , 2005, Journal of cellular physiology.

[17]  Liang Cheng,et al.  OCT4 Immunohistochemistry Is Superior to Placental Alkaline Phosphatase (PLAP) in the Diagnosis of Central Nervous System Germinoma , 2005, The American journal of surgical pathology.

[18]  A. Rizzino,et al.  Transcription factor sox‐2 inhibits co‐activator stimulated transcription , 2004, Molecular reproduction and development.

[19]  J. Marrero,et al.  Newer markers for hepatocellular carcinoma. , 2004, Gastroenterology.

[20]  T. Burdon,et al.  Oct‐4 Knockdown Induces Similar Patterns of Endoderm and Trophoblast Differentiation Markers in Human and Mouse Embryonic Stem Cells , 2004, Stem cells.

[21]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Testa,et al.  Chromosomal imbalances in human lung cancer , 2002, Oncogene.

[23]  B. Stripp,et al.  Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. , 2002, The American journal of pathology.

[24]  C. Holding,et al.  Human embryonic genes re-expressed in cancer cells , 2001, Oncogene.

[25]  I. Weissman,et al.  Stem cells, cancer, and cancer stem cells , 2001, Nature.

[26]  M. Weiss,et al.  Floppy SOX: mutual induced fit in hmg (high-mobility group) box-DNA recognition. , 2001, Molecular endocrinology.

[27]  M. Wegner,et al.  From head to toes: the multiple facets of Sox proteins. , 1999, Nucleic acids research.

[28]  M. Czuczman,et al.  Use of rituximab, the new FDA-approved antibody. , 1998, Current opinion in oncology.

[29]  H. Schöler,et al.  Formation of Pluripotent Stem Cells in the Mammalian Embryo Depends on the POU Transcription Factor Oct4 , 1998, Cell.

[30]  R. Lovell-Badge,et al.  Sox genes find their feet. , 1997, Current opinion in genetics & development.

[31]  P N Goodfellow,et al.  SRY, like HMG1, recognizes sharp angles in DNA. , 1992, The EMBO journal.

[32]  H. Schöler,et al.  A family of octamer‐specific proteins present during mouse embryogenesis: evidence for germline‐specific expression of an Oct factor. , 1989, The EMBO journal.

[33]  J. Till Stem cells in differentiation and neoplasia , 1982, Journal of cellular physiology. Supplement.