Transcription factor 7 promotes the progression of perihilar cholangiocarcinoma by inducing the transcription of c-Myc and FOS-like antigen 1.
BACKGROUND
Perihilar cholangiocarcinoma (PHCC) is the most common type of cholangiocarcinoma with the worst prognosis. Radical resection of PHCC is difficult; thus, few effective biomarkers or useful molecular profiles for PHCC have been reported in recent years. Therefore, in this study, we aimed to assess biomarkers for PHCC.


METHODS
We screened potential biomarkers for PHCC using exome and transcriptome sequencing with PHCC tissues and paired normal tissues. Transcription factor 7 (TCF7) expression was evaluated using quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemistry. The correlations between TCF7 and clinicopathological factors were analyzed with Chi-square test, and the prognostic significance of TCF7 was evaluated with univariate and multivariate analyses. The functions of TCF7 and its main effectors in PHCC cells were investigated in vitro and in vivo.


FINDINGS
TCF7 expression was upregulated in PHCC and was an unfavorable prognostic biomarker. c-Myc was a main effector of TCF7 in PHCC cells and modulated TCF7-induced proliferation, invasion, and migration. FOS-like antigen 1 (FOSL1) was identified as a downstream target of TCF7 and was required in TCF7-induced PHCC proliferation. Triple-positive expression of TCF7, c-Myc, and FOSL1 predicted a much worse prognosis in patients with PHCC than TCF7 expression alone.


INTERPRETATION
Postoperative detection of TCF7, c-Myc, and FOSL1 may be useful for stratifying patients with a high risk of unfavorable prognosis, and suppressing TCF7 or its downstream effectors may be a promising strategy for the treatment of PHCC.
['Liu|Zengli|Z|', 'Sun|Rongqi|R|', 'Zhang|Xiaoming|X|', 'Qiu|Bo|B|', 'Chen|Tianli|T|', 'Li|Zhipeng|Z|', 'Xu|Yunfei|Y|', 'Zhang|Zongli|Z|']
D000368:Aged D001653:Bile Ducts, Intrahepatic D014408:Biomarkers, Tumor D045744:Cell Line, Tumor D018450:Disease Progression D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D018285:Klatskin Tumor D008297:Male D008875:Middle Aged D011379:Prognosis D016760:Proto-Oncogene Proteins c-fos D016271:Proto-Oncogene Proteins c-myc D051822:T Cell Transcription Factor 1
Transcription factor 7 Progression Perihilar cholangiocarcinoma C-Myc FOS-like antigen 1 Prognosis