The prognostic and immune significance of Rab11A in pan-cancer and its function and mechanism underlying estrogen receptor targeting in breast cancer

Yilun Li; Baifang Ding; Mengyu Wei; Xiaolu Yang; Ruihuan Fu; Yinfeng Liu; Lin Zhu; Yan Ding; Wenjin Zhang; Geng Zhang; Shuo Zhang; Yuhui Bu; Jianchao He; Jianye Deng; Xiaohuan Bao; Jun Hao; Li Ma

doi:10.1111/ajco.14130

The prognostic and immune significance of Rab11A in pan-cancer and its function and mechanism underlying estrogen receptor targeting in breast cancer

Asia Pac J Clin Oncol. 2024 Oct 12. doi: 10.1111/ajco.14130. Online ahead of print.

Authors

Yilun Li¹, Baifang Ding², Mengyu Wei¹, Xiaolu Yang¹, Ruihuan Fu¹, Yinfeng Liu¹, Lin Zhu³, Yan Ding⁴, Wenjin Zhang¹, Geng Zhang¹, Shuo Zhang¹, Yuhui Bu¹, Jianchao He¹, Jianye Deng¹, Xiaohuan Bao¹, Jun Hao⁵, Li Ma¹

Affiliations

¹ Department of Breast Disease Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
² Department of Breast Surgery, Panjin central hospital, Panjin, China.
³ Department of Electromyogram, the Third Hospital of Hebei Medical University, Shijiazhuang, China.
⁴ Department of Pathology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
⁵ Department of Pathology, Hebei Medical University, Shijiazhuang, China.

PMID: 39395024
DOI: 10.1111/ajco.14130

Abstract

Objective: Rab11A is an important molecule for recycling endosomes and is closely related to the proliferation, invasion, and metastasis of tumors. This study investigated the prognostic and immune significance of Rab11A and validated its potential function and mechanism in breast cancer (BRCA).

Methods: RNA sequencing data for 33 tumors were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases. Correlation analysis was used to evaluate the relationship between Rab11A expression and immune characteristics. Potential pathways were identified using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis. Immunohistochemical analysis, colony formation assay, bromodeoxyuridine incorporation assay, immunofluorescence, and Western blot were used to explore potential function and mechanism.

Results: Analysis of the TCGA database showed significant upregulation of Rab11A expression in a variety of cancers. Rab11A was up-regulated in 82.4% of BRCA. High Rab11A expression is associated with poor survival in cancer patients and is a predictor of poor prognosis. CIBERSORT analysis showed that Rab11A was negatively associated with almost all immune cycle activity scores pan-cancer. The results of the TCGA-BRCA cohort were further confirmed by using pathological samples from clinical BRCA patients. The results showed that Rab11A expression was correlated with estrogen receptor (ER) and progesterone receptor expression in BRCA (p < 0.05). Knockdown and overexpression of Rab11A affected the proliferation of BRCA cells. Further mechanistic studies revealed that down-regulation of ER alpha (ERα) and up-regulation of ER beta (ERβ) mediated Rab11A-induced inhibition of BRCA cell proliferation.

Conclusion: Rab11A expression in pan-cancer is associated with poor prognosis and immune profile. In particular, in BRCA, Rab11A expression regulates cell proliferation by targeting ERα and ERβ. High Rab11A expression is tightly associated with immune characteristics, tumor microenvironment, and genetic mutations. These results provide a reference for exploring the role of Rab11A in pan-cancer and provide a new perspective for revealing potential therapeutic targets in BRCA.

Keywords: ER; Rab11A; immune characteristics; pan‐cancer; prognosis.

Abstract

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