Dataset Information

Clinical and molecular characteristics of RNF43 mutations as promising prognostic biomarkers in colorectal cancer.

ABSTRACT:

Background

Transmembrane E3 ubiquitin ligase (RNF43) mutations are present in approximately 6-18% of colorectal cancers (CRC) and could enhance Wnt/β-catenin signaling, which is emerging as a promising therapeutic target. This study aims to investigate the clinical and molecular characteristics and potential heterogeneity of RNF43-mutant CRC.

Methods

A total of 78 patients with RNF43-mutant CRC were enrolled from July 2013 to November 2022. Demographic data, clinical characteristics, treatment regimens used, and survival outcomes were collected and analyzed.

Results

Our study uncovered that patients with RNF43 mutations in the N-terminal domain (NTD; n = 50) exhibited shorter overall survival (OS; median months, 50.80 versus not reached; p = 0.043) compared to those in the C-terminal domain (CTD; n = 17). Most RNF43 mutations in NTD had positive primary lymph node status, low tumor mutation burden (TMB-L), and correlated with proficient mismatch repair (pMMR)/microsatellite stable (MSS) status. By contrast, RNF43 mutations in CTD were significantly enriched in deficient MMR (dMMR)/microsatellite instability (MSI-H) tumors with high TMB (TMB-H). N-terminal RNF43-mutated tumors harbored a hotspot variant (RNF43 R117fs), which independently predicted a significantly worse outcome in pMMR/MSS CRC with a median OS of 18.9 months. Patients with RNF43 mutations and the BRAF V600E alterations demonstrated sensitivity to BRAF/EGFR inhibitors. Moreover, we observed that pMMR/MSS patients with RNF43 R117fs mutation had a higher incidence of stage IV, ⩾2 metastatic sites, low TMB, and none of them received PD-1/PD-L1 inhibitor therapy.

Conclusion

Our findings provide the first evidence that RNF43 mutations in NTD and the R117fs variant correlate with a poorer prognosis in CRC patients, providing strategies for Wnt-targeted therapy to improve clinical efficacy.

SUBMITTER: Huang ZY

PROVIDER: S-EPMC10777808 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Clinical and molecular characteristics of <i>RNF43</i> mutations as promising prognostic biomarkers in colorectal cancer.

Huang Zi-Yao ZY Wen Lei L Ye Liu-Fang LF Lu Yu-Ting YT Pat Fong William W Zhang Ren-Jing RJ Wu Si-Xian SX Chen Zhi-Gang ZG Cai Yan-Yu YY Xu Rui-Hua RH Li Yu-Hong YH Du Zi-Ming ZM Wang De-Shen DS

Therapeutic advances in medical oncology 20240109

<h4>Background</h4>Transmembrane E3 ubiquitin ligase (<i>RNF43</i>) mutations are present in approximately 6-18% of colorectal cancers (CRC) and could enhance Wnt/β-catenin signaling, which is emerging as a promising therapeutic target. This study aims to investigate the clinical and molecular characteristics and potential heterogeneity of <i>RNF43</i>-mutant CRC.<h4>Methods</h4>A total of 78 patients with <i>RNF43</i>-mutant CRC were enrolled from July 2013 to November 2022. Demographic data, c ...[more]

PMID: 38205077

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