RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer

Peipei Shang; Jiongjiong Lu; Feihong Song; Yijun Zhao; Weipeng Hong; Yuange He; Weidong Shen; Li Geng

doi:10.3389/fonc.2023.1119587

RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer

Front Oncol. 2023 Jun 20:13:1119587. doi: 10.3389/fonc.2023.1119587. eCollection 2023.

Authors

Peipei Shang¹, Jiongjiong Lu², Feihong Song², Yijun Zhao², Weipeng Hong³, Yuange He³, Weidong Shen³, Li Geng²

Affiliations

¹ Oncology Department, Eastern Hepatobiliary Surgical Hospital, Shanghai, China.
² Department of Special Treatment, Eastern Hepatobiliary Surgical Hospital, Shanghai, China.
³ Department of Medical Center, Geneplus-Beijing Ltd., Beijing, China.

Abstract

Background: Colorectal cancer (CRC) patients with BRAF mutation have very poor prognosis. It is urgent to search for prognostic factors of BRAF mutant CRC. RNF43 is a ENF ubiquitin ligase of Wnt signaling. Mutation of RNF43 has been observed frequently in various types of human cancers. However, few studies have evaluated the role of RNF43 in CRC. The present study aimed to explore the impact of RNF43 mutations on molecular characteristics and prognosis in BRAF mutant CRC.

Methods: Samples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation.

Results: This study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC.

Conclusion: Collectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients.

Keywords: BRAF; RNF43; clinical outcome; colorectal cancer; genomic features.

Grants and funding

This research has received funding from the “Clinicalscience and technology innovation project of Shenkang Hospital Development Center” (SHDC12020104).