본문 바로가기
KERD
논문KCI 등재

Correlation of Cancer Stem-Cell Markers OCT4, SOX2, and NANOG with Clinicopathological Features and Prognosis in Operative Patients with Rectal Cancer

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류의학일반

초록

Purpose: To investigate the association of cancer stem-cell markers [octamer-binding transcription factor 4 (OCT4), sex determiningregion Y-box 2 (SOX2), and Nanog homebox (NANOG)] expression with clinicopathological properties and overall survival (OS) in operative rectal cancer (RC) patients receiving adjuvant therapy. Materials and Methods: 153 patients with primary RC receiving surgery were enrolled. Tumor tissue and paired adjacent normal tissue sample were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunofluorescent staining. The medianfollow-up duration was 5.2 years, and the last follow-up date was August 2016. Results: Tumor tissue OCT4 (p<0.001), SOX2 (p=0.003), and NANOG (p<0.001) expressions were higher than those in adjacent tissue. OCT4 expression was positively correlated with pathological grade (R=0.185, p=0.022), tumor size (R=0.224, p=0.005), and N stage (R=0.170, p=0.036). NANOG expression was positively associated with tumor size (R=0.169, p=0.036). Kaplan-Meier suggestedthat OCT4+ was associated with worse OS compared with OCT4− (p<0.001), while no association of SOX2 (p=0.121) and NANOG expressions (p=0.195) with OS was uncovered. Compared with one or no positive marker, at least two positive markers were associated with shorter OS (p<0.001), while all three positive markers were correlated with worse OS compared with two or less positive markers (p<0.001). Multivariate Cox’s analysis revealed that OCT4+ (p<0.001) and N stage (p=0.046) were independentfactors for shorter OS. Conclusion: Tumor tissue OCT4 expression was correlated with poor differentiation, tumor size, and N stage, and it can serve as an independent prognostic biomarker in operative patients with RC receiving adjuvant therapy.

Abstract

Purpose: To investigate the association of cancer stem-cell markers [octamer-binding transcription factor 4 (OCT4), sex determiningregion Y-box 2 (SOX2), and Nanog homebox (NANOG)] expression with clinicopathological properties and overall survival (OS) in operative rectal cancer (RC) patients receiving adjuvant therapy. Materials and Methods: 153 patients with primary RC receiving surgery were enrolled. Tumor tissue and paired adjacent normal tissue sample were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunofluorescent staining. The medianfollow-up duration was 5.2 years, and the last follow-up date was August 2016. Results: Tumor tissue OCT4 (p<0.001), SOX2 (p=0.003), and NANOG (p<0.001) expressions were higher than those in adjacent tissue. OCT4 expression was positively correlated with pathological grade (R=0.185, p=0.022), tumor size (R=0.224, p=0.005), and N stage (R=0.170, p=0.036). NANOG expression was positively associated with tumor size (R=0.169, p=0.036). Kaplan-Meier suggestedthat OCT4+ was associated with worse OS compared with OCT4− (p<0.001), while no association of SOX2 (p=0.121) and NANOG expressions (p=0.195) with OS was uncovered. Compared with one or no positive marker, at least two positive markers were associated with shorter OS (p<0.001), while all three positive markers were correlated with worse OS compared with two or less positive markers (p<0.001). Multivariate Cox’s analysis revealed that OCT4+ (p<0.001) and N stage (p=0.046) were independentfactors for shorter OS. Conclusion: Tumor tissue OCT4 expression was correlated with poor differentiation, tumor size, and N stage, and it can serve as an independent prognostic biomarker in operative patients with RC receiving adjuvant therapy.

참고문헌 (39)

  1. Li X, "Negative lymph node count is an independent prognostic factor for patients with rectal cancer who received preoperative radiotherapy", BMC Cancer, 17, pp.227~ (2017)[DOI]
  2. Siegel RL, "Cancer statistics, 2016", CA Cancer J Clin, 66, pp.7~30 (2016)[DOI]
  3. Torre LA, "Global cancer statistics, 2012", CA Cancer J Clin, 65, pp.87~108 (2015)[DOI]
  4. Hoecht S, "Treatment of rectal cancer", N Engl J Med, 355, pp.2486~ (2006)[DOI]
  5. Beck B, "Unravelling cancer stem cell potential", Nat Rev Cancer, 13, pp.727~738 (2013)[DOI]
  6. Cao L, "OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma", BMC Cancer, 13, pp.82~ (2013)[DOI]
  7. Zhou Xi, "Over-Expression of Oct4 in Human Esophageal Squamous Cell Carcinoma", Molecules and Cells, 32(1), pp.39~45 (2011), 한국분자세포생물학회
  8. Lin J, "MiR-26b", KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4, 2015, pp.6, 23793~23806
  9. Jaenisch R, "Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming", Cell, 132, pp.567~582 (2008)[DOI]
  10. Neumann J, "SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer", BMC Cancer, 11, pp.518~ (2011)[DOI]
  11. Lessey BA, "Aberrant integrin expression in the endometrium of women with endometriosis", J Clin Endocrinol Metab, 79, pp.643~649 (1994)
  12. Kashyap V, "Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs", Stem Cells Dev, 18, pp.1093~1108 (2009)[DOI]
  13. Wang YD, "OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b", BAK1 pathway, 2013, pp.4, e760~
  14. Tang YA, "Global Oct4 target gene analysis reveals novel downstream PTEN and TNC genes required for drug-resistance and metastasis in lung cancer", Nucleic Acids Res, 43, pp.1593~1608 (2015)[DOI]
  15. Wu Y, "Up-regulation of microRNA-145 promotes differentiation by repressing OCT4 in human endometrial adenocarcinoma cells", Cancer, 117, pp.3989~3998 (2011)[DOI]
  16. Yu B, "Expressions of stem cell transcription factors Nanog and Oct4 in renal cell carcinoma tissues and clinical significance", Artif Cells Nanomed Biotechnol, 44, pp.1818~1823 (2016)[DOI]
  17. Li X, "Expression of Sox2 and Oct4 and their clinical significance in human non-small-cell lung cancer", Int J Mol Sci, 13, pp.7663~7675 (2012)[DOI]
  18. Li C, "OCT4 positively regulates Survivin expression to promote cancer cell proliferation and leads to poor prognosis in esophageal squamous cell carcinoma", PLoS One, 7, pp.e49693~ (2012)[DOI]
  19. Matsuoka J, "Role of the stemness factors sox2, oct3", 4, and nanog in gastric carcinoma, 2012, pp.174, 130~135
  20. Atlasi Y, "OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer", Int J Cancer, 120, pp.1598~1602 (2007)[DOI]
  21. Chiou SH, "Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma", Clin Cancer Res, 14, pp.4085~4095 (2008)[DOI]
  22. Shen L, "High expression of SOX2 and OCT4 indicates radiation resistance and an independent negative prognosis in cervical squamous cell carcinoma", J Histochem Cytochem, 62, pp.499~509 (2014)[DOI]
  23. Linn DE, "A role for OCT4 in tumor initiation of drug-resistant prostate cancer cells", Genes Cancer, 1, pp.908~916 (2010)[DOI]
  24. Li B, "Overexpression of OCT4 is associated with gefitinib resistance in non-small cell lung cancer", Oncotarget, 7, pp.77342~77347 (2016)
  25. Sullivan JP, "Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy", Cancer Metastasis Rev, 29, pp.61~72 (2010)[DOI]
  26. Li W, "Dual inhibiting OCT4 and AKT potently suppresses the propagation of human cancer cells", Sci Rep, 7, pp.46246~ (2017)[DOI]
  27. Emhemmed F, "Selective anticancer effects of a synthetic flavagline on human Oct4-expressing cancer stem-like cells via a p38 MAPK-dependent caspase-3-dependent pathway", Biochem Pharmacol, 89, pp.185~196 (2014)[DOI]
  28. Yong X, "Helicobacter pylori upregulates Nanog and Oct4 via Wnt", <TEX>${\beta}$<, Cancer Lett, pp.2016, 374[DOI]
  29. Teng HF, "Valproic acid enhances Oct4 promoter activity through PI3K", Akt, Mol Cell Endocrinol, pp.2014, 383[DOI]
  30. "Rectal Cancer Treatment (PDQ(R)): Health Professional Version;PDQ Cancer Information Summaries" (2002), National Cancer Institute
  31. Al-Marzoqee FY, "Upregulation and inhibition of the nuclear translocation of Oct4 during multistep gastric carcinogenesis", Int J Oncol, 41, pp.1733~1743 (2012)[DOI]
  32. Wen Y, "SOX2 is required to maintain cancer stem cells in ovarian cancer", Cancer Sci, 108, pp.719~731 (2017)[DOI]
  33. Xiao L, "Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide- induced acute uterine injury and intrauterine adhesions", Reprod Biol Endocrinol, 15, pp.14~ (2017)[DOI]
  34. Piva M, "Sox2 promotes tamoxifen resistance in breast cancer cells", EMBO Mol Med, 6, pp.66~79 (2014)[DOI]
  35. Bass AJ, "SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas", Nat Genet, 41, pp.1238~1242 (2009)[DOI]
  36. Sodja E, "The prognostic value of whole blood SOX2, NANOG and OCT4 mRNA expression in advanced small-cell lung cancer", Radiol Oncol, 50, pp.188~196 (2016)
  37. Yamawaki K, "Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer", Cancer Sci, 108, pp.632~640 (2017)[DOI]
  38. Velcheti V, "High SOX2 levels predict better outcome in non-small cell lung carcinomas", PLoS One, 8, pp.e61427~ (2013)[DOI]
  39. Sholl LM, "Sox2 protein expression is an independent poor prognostic indicator in stage I lung adenocarcinoma", Am J Surg Pathol, 34, pp.1193~1198 (2010)[DOI]

관련 논문AI추천

Clinicopathologic Significance of Survivin Expression in Relation to CD133 Expression in Surgically Resected Stage II or III Colorectal Cancer이미라, 조미연, 최은희, Wanlu Li대한병리학회 · Journal of Pathology and Translational Medicine2017 · 제51권 제1호CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance권희정, 김경주, 김민종, 배영경대한병리학회 · Journal of Pathology and Translational Medicine2016 · 제50권 제6호Overexpression of SOX2 Is Associated with Better Overall Survival in Squamous Cell Lung Cancer Patients Treated with Adjuvant Radiotherapy금기창, 김용배, 김철훈, 박규현, 윤홍인, 이은정, 이창걸대한암학회 · Cancer Research and Treatment2016 · 제48권 제2호mTOR Signaling Combined with Cancer Stem Cell Markers as a Survival Predictor in Stage II Colorectal Cancer강조연, 김원호, 김재현, 김태일, 김호근, 박수정, 박예현, 박재준, 장지영, 천재희연세대학교의과대학 · Yonsei Medical Journal2020 · 제61권 제7호Clinicopathologic Implications of PIWIL2 Expression in Colorectal Cancer김수미, 김영옥, 오선주, 장희경대한병리학회 · Journal of Pathology and Translational Medicine2012 · 제46권 제4호KLF4 Expression Correlates with the Degree of Differentiation in Colorectal CancerChao Liu, Li Zuo, Qiang Wu, Qing Zhou, Ruolei Hu, Shuyu Gui, Sumei Zhang, Wei Wei, Yan Zuo, Yuan Wang거트앤리버 소화기연관학회협의회 · Gut and Liver2011 · 제5권 제2호

이 간행물의 다른 논문 (12건)