Wang Xiu, Li Xinyu, Jiang Wenying
Department of Breast Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Department of Radiology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Transl Cancer Res. 2023 Apr 28;12(4):859-872. doi: 10.21037/tcr-22-2350. Epub 2023 Mar 27.
RTN4IP1 interacts with a membranous protein of endoplasmic reticulum (RTN4), this study was to explore the role RTN4IP1 involved in breast cancer (BC).
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.
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 BC had worse DSS than RTN4IP1 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).
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.
RTN4IP1与内质网的一种膜蛋白（RTN4）相互作用，本研究旨在探讨RTN4IP1在乳腺癌（BC）中的作用。
下载癌症基因组图谱乳腺浸润性癌（TCGA-BRCA）项目的RNAseq数据，检测RTN4IP1表达与临床病理变量之间的相关性，以及癌组织样本和非癌组织样本之间的表达水平。进行差异表达基因（DEG）和功能富集、基因集富集分析（GSEA）和免疫浸润分析以进行生物信息学分析。经过逻辑回归、疾病特异性生存（DSS）的Kaplan-Meier曲线、单因素和多因素COX分析，建立了预后列线图。
RTN4IP1在BC组织中表达上调，与雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）状态显著相关（P<0.001）。771个DEG将RTN4IP1与谷氨酰胺代谢和线粒体核糖体相关的质量控制联系起来。功能富集指向DNA代谢过程、线粒体基质和内膜、ATP酶活性、细胞周期和细胞衰老；而GSEA表明细胞周期调控、G1_S DNA损伤检查点、耐药性和转移。发现嗜酸性粒细胞、自然杀伤（NK）细胞和Th 2细胞与RTN4IP1表达相关（分别为R=-0.290、-0.277和0.266，P<0.001）。RTN高表达的BC患者的DSS比RTN低表达者更差[风险比（HR）=2.37，95%置信区间（CI）：（1.48-3.78），P<0.001]，具有独立的预后价值（P<0.05）。
RTN4IP1在BC组织中过表达，可预测BC患者的不良预后，尤其是在浸润性导管癌、浸润性小叶癌、II期、III&IV期和管腔A型亚型中。
