Identification of a prognostic signature and ENTR1 as a prognostic biomarker for colorectal mucinous adenocarcinoma

An Huang; Jingyi Shi; Zhuang Sun; Yong Yang; Zhaoya Gao; Jin Gu

doi:10.3389/fonc.2023.1061785

Identification of a prognostic signature and ENTR1 as a prognostic biomarker for colorectal mucinous adenocarcinoma

Front Oncol. 2023 Apr 27:13:1061785. doi: 10.3389/fonc.2023.1061785. eCollection 2023.

Authors

An Huang¹, Jingyi Shi¹, Zhuang Sun¹, Yong Yang², Zhaoya Gao^{2

3}, Jin Gu^{1

2

4}

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, Beijing, China.
² Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China.
³ Department of General Surgery, Peking University First Hospital, Beijing, China.
⁴ Peking Tsinghua Center for Life Science, Peking University International Cancer Center, Beijing, China.

Abstract

Background: Mucinous adenocarcinoma (MAC) is a unique clinicopathological colorectal cancer (CRC) type that has been recognized as a separate entity from non-mucinous adenocarcinoma (NMAC), with distinct clinical, pathologic, and molecular characteristics. We aimed to construct prognostic signatures and identifying candidate biomarkers for patients with MAC.

Methods: Differential expression analysis, weighted correlation network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model were used to identify hub genes and construct a prognostic signature based on RNA sequencing data from TCGA datasets. The Kaplan-Meier survival curve, gene set enrichment analysis (GSEA), cell stemness, and immune infiltration were analyzed. Biomarker expression in MAC and corresponding normal tissues from patients operated in 2020 was validated using immunohistochemistry.

Results: We constructed a prognostic signature based on ten hub genes. Patients in the high-risk group had significantly worse overall survival (OS) than patients in the low-risk group (p < 0.0001). We also found that ENTR1 was closely associated with OS (p = 0.016). ENTR1 expression was significantly positively correlated with cell stemness of MAC (p < 0.0001) and CD8+ T cell infiltration (p = 0.01), whereas it was negatively associated with stromal scores (p = 0.03). Finally, the higher expression of ENTR1 in MAC tissues than in normal tissues was validated.

Conclusion: We established the first MAC prognostic signature, and determined that ENTR1 could serve as a prognostic marker for MAC.

Keywords: ENTR1; biomarker; colorectal cancer; mucinous adenocarcinoma; prognosis.

Grants and funding

This research was funded by Capital’s Funds for Health Improvement and Research of China (CFH 2020-1-6041) and the National Natural Science Foundation of China (82073223).