High C16orf74 expression correlates with poor survival in extrahepatic cholangiocarcinoma
Investigators evaluated C16orf74 protein expression in 146 resected extrahepatic cholangiocarcinoma specimens using immunohistochemistry and assessed its prognostic and functional relevance. High C16orf74 expression was observed in 45.2% of tumors and independently predicted worse overall survival, with a 5-year survival rate of 27.2% compared to 52.2% in low-expression cases. Preclinical models demonstrated that a C16orf74-targeting dimer-blocking peptide suppressed tumor growth and impaired cell migration through Akt/mTOR pathway modulation. For diagnostic laboratories, the findings position C16orf74 as a potential prognostic marker, though clinical implementation requires prospective assay validation and standardized testing protocols.
The original study
Clinical and Functional Significance of
- Authors
- Kimura K, Nakamura T, Kushibiki T, Fujii M, Kuraya T, Niwa H, et al.
- Journal
- Anticancer research
- Type
- Journal Article
- PMID
- 42527075
Original abstract
BACKGROUND/AIM: Biliary tract cancer (BTC) is an aggressive malignancy associated with a poor prognosis, yet effective molecular therapeutic targets remain scarce. Chromosome 16 open reading frame 74 (C16orf74) has been implicated in tumor progression; however, its specific role in BTC remains unclear. This study aimed to investigate the prognostic significance of C16orf74 in extrahepatic cholangiocarcinoma (eCCA) and to evaluate its potential as a therapeutic target. MATERIALS AND METHODS: We evaluated C16orf74 protein expression in 146 resected eCCA specimens using immunohistochemistry. Functional analyses in BTC cell lines included reverse transcription-polymerase chain reaction, cell proliferation assays, and migration and invasion assays, followed by the evaluation of downstream Akt/mTOR signaling. The in vivo antitumor efficacy of a C16orf74-targeting dimer-blocking (DB) peptide was assessed using a murine xenograft model. RESULTS: High C16orf74 expression occurred in 45.2% of the tumors and was associated with worse overall survival (5-year survival rate: 27.2% vs. 52.2%). Although this association only trended toward significance following false discovery rate adjustment in the univariate analysis, high C16orf74 expression remained an independent predictor of worse survival in the multivariate analysis. In vitro, the DB peptide inhibited cellular migration and invasion and induced dose-dependent cytotoxicity in C16orf74-high cell lines; these effects were accompanied by decreased Akt phosphorylation. In vivo, DB peptide treatment suppressed tumor growth in the TFK-1 xenograft model. CONCLUSION: High C16orf74 expression is associated with a poor prognosis in patients with resected eCCA. Furthermore, targeting C16orf74 with a DB peptide demonstrates substantial antitumor activity. Therefore, C16orf74 represents a promising prognostic biomarker and a potential therapeutic target for eCCA.