High expression of RTN4IP1 predicts adverse prognosis for patients with breast cancer

Xiu Wang; Xinyu Li; Wenying Jiang

doi:10.21037/tcr-22-2350

High expression of RTN4IP1 predicts adverse prognosis for patients with breast cancer

Transl Cancer Res. 2023 Apr 28;12(4):859-872. doi: 10.21037/tcr-22-2350. Epub 2023 Mar 27.

Authors

Xiu Wang¹, Xinyu Li¹, Wenying Jiang^{1

2}

Affiliations

¹ Department of Breast Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.
² Department of Radiology, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Abstract

Background: RTN4IP1 interacts with a membranous protein of endoplasmic reticulum (RTN4), this study was to explore the role RTN4IP1 involved in breast cancer (BC).

Methods: After RNAseq data of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) project were downloaded, correlations between RTN4IP1 expression and clinicopathologic variables, as well as expression levels between cancerous samples and non-cancerous ones were tested. Differentially expressed genes (DEGs) and functional enrichment, gene set enrichment analysis (GSEA) and immune infiltration analysis were conduct for bioinformatics analysis. After logistic regression, Kaplan-Meier curve of disease-specific survival (DSS), univariate and multivariate COX analysis, a nomogram was established for prognosis.

Results: RTN4IP1 expression was up-regulated in BC tissue, significantly associated with estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status (P<0.001). The 771 DEGs linked RTN4IP1 to glutamine metabolism and mitoribosome-associated quality control. Functional enrichment pointed to DNA metabolic process, mitochondrial matrix and inner membrane, ATPase activity, cell cycle and cellular senescence; whereas GSEA indicated regulation of cellular cycle, G1_S DNA damage checkpoints, drug resistance and metastasis. Eosinophil cells, natural killer (NK) cells and Th 2 cells were found to be correlated with RTN4IP1 expression (R=-0.290, -0.277 and 0.266, respectively, P<0.001). RTN4IP1^high BC had worse DSS than RTN4IP1^low ones [hazard ratio (HR) =2.37, 95% confidential interval (CI): (1.48-3.78), P<0.001], which has independent prognostic value (P<0.05).

Conclusions: Overexpressed in BC tissue, RTN4IP1 predicts adverse prognosis for patients with BC, especially in infiltrating ductal carcinoma, infiltrating lobular carcinoma, Stage II, Stages III&IV and luminal A subtype.

Keywords: RTN4IP1; breast cancer (BC); mitochondria; prognosis.