title: Correlation of STAT1 with apoptosis and cell-cycle markers in esophageal squamous cell carcinoma.
abstract: We recently found evidence that STAT1 in esophageal squamous carcinoma (ESCC) cells exerts tumor suppressor function, and it regulates five key regulators of apoptosis or cell-cycle progression, including Bcl-2, Bcl-xL, survivin, cyclin D1 and p21. In this study, we confirmed these findings in four ESCC cell lines. Using immunohistochemistry, we also assessed the expression of these proteins in 62 primary tumors. The expression of these markers was heterogeneous, ranging 39 to 69% of the cohort. Significant correlation was found between STAT1 and three proteins (p21, Bcl-xL and survivin), whereas only a trend was identified for cyclin D1 and Bcl-2. We then correlated the expression of these proteins with several clinicopathologic parameters including lymph node metastasis, depth of invasion, clinical stage and overall survival. Significant correlations were found between Bcl-2 and deep invasion (p = 0.033), survivin and lymph node metastasis (p = 0.006), as well as cyclin D1 and clinical stage (p = 0.014). Patients with p21-positive tumors had a significantly longer survival compared to those with p21-negative tumors (p = 0.031). To conclude, our findings support the concept that STAT1 exerts its tumor suppressor effects in ESCC via modulating the expression of key regulators of apoptosis and cell-cycle progression.
authors.affiliation: Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Yun
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.affiliation: Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D050794:STAT1 Transcription Factor / Q000032:analysis* / Q000378:metabolism; D000077022:Survivin; D051020:bcl-X Protein / Q000032:analysis / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000077022:Survivin; D051020:bcl-X Protein