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mTOR Signaling Combined with Cancer Stem Cell Markers as a Survival Predictor in Stage II Colorectal Cancer

 Ji Young Chang  ;  Jae Hyun Kim  ;  Joyeon Kang  ;  Yehyun Park  ;  Soo Jung Park  ;  Jae Hee Cheon  ;  Won Ho Kim  ;  Hoguen Kim  ;  Jae Jun Park  ;  Tae Il Kim 
 YONSEI MEDICAL JOURNAL, Vol.61(7) : 572-578, 2020-07 
Journal Title
Issue Date
Antigens, CD / metabolism* ; Biomarkers, Tumor / analysis* ; Biomarkers, Tumor / metabolism ; Colonic Neoplasms / metabolism ; Colonic Neoplasms / mortality ; Colonic Neoplasms / pathology ; Colorectal Neoplasms / metabolism* ; Colorectal Neoplasms / mortality ; Colorectal Neoplasms / pathology* ; Disease-Free Survival ; Female ; Humans ; Hyaluronan Receptors ; Male ; Middle Aged ; Neoplasm Staging ; Neoplastic Stem Cells / drug effects ; Neoplastic Stem Cells / metabolism* ; Neoplastic Stem Cells / pathology* ; Neoplastic Stem Cells / transplantation ; Prognosis ; Signal Transduction ; TOR Serine-Threonine Kinases / analysis ; TOR Serine-Threonine Kinases / metabolism* ; beta Catenin
Neoplastic stem cell ; carcinogenesis ; colorectal cancer ; prognosis ; survival
Purpose: Wnt and mammalian target of rapamycin (mTOR) are major molecular signaling pathways associated with the development and progression of tumor, as well as the maintenance and proliferation of cancer stem cells (CSCs), in colorectal cancer (CRC). Identifying patients at risk of poor prognosis is important to determining whether to add adjuvant treatment in stage II CRC and thus improve survival. In the present study, we evaluated the prognostic value of Wnt, mTOR, and CSC markers as survival predictors in stage II CRC.

Materials and methods: We identified 148 cases of stage II CRC and acquired their tumor tissue. Tissue microarrays for immunohistochemical staining were constructed, and the expressions of CD166, CD44, EphB2, β-catenin, pS6 were evaluated using immunohistochemical staining.

Results: The expressions of CD166 (p=0.045) and pS6 (p=0.045) and co-expression of pS6/CD166 (p=0.005), pS6/CD44 (p=0.042), and pS6/CD44/CD166 (p=0.013) were negatively correlated with cancer-specific survival. Cox proportional hazard analysis showed the combination of CD166/pS6 [hazard ratio, 9.42; 95% confidence interval, 2.36-37.59; p=0.002] to be the most significant predictor related with decreased cancer-specific survival. In addition, co-expression of CD44/CD166 (p=0.017), CD166/β-catenin (p=0.036), CD44/β-catenin (p=0.001), and CD44/CD166/β-catenin (p=0.001) were significant factors associated with liver metastasis.

Conclusion: Specific combinations of CSC markers and β-catenin/mTOR signaling could be a significant predictor of poor survival in stage II CRC.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Kim, Hogeun(김호근)
Park, Soo Jung(박수정)
Park, Yehyun(박예현) ORCID logo https://orcid.org/0000-0001-8811-0631
Park, Jae Jun(박재준)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
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