CRIM1水平低预示乳腺癌患者预后不良。

Low CRIM1 Levels Predict Poor Prognosis in Breast Cancer Patients.

作者信息

Wen Wei, Jiang Baohong, Cao Xi, Xie Liming, Zhang Xiaoli, Li Yuehua, He Rongfang

机构信息

Department of Pathology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.

Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.

出版信息

Front Oncol. 2022 May 6;12:882328. doi: 10.3389/fonc.2022.882328. eCollection 2022.

DOI:10.3389/fonc.2022.882328

PMID:35600360

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9120825/

Abstract

BACKGROUND

CRIM1 is involved in the development and preservation of the nervous system, capillary development, and vascular maintenance. Although CRIM1 was reported to involve in multiple cancers, its role in breast cancer is unclear.

METHODS

We investigated CRIM1 expression levels using Oncomine, HPA, and immunohistochemistry analyses. BC-GenExMiner was employed to evaluate the relationship of CRIM1 expression with the clinicopathological characteristics of breast cancer. Its association with breast cancer prognosis was assessed by Kaplan-Meier analysis and PrognoScan. The correlation of the expression of CRIM1 with tumor immune infiltration was explored TIMER. Gene set enrichment analysis (GSEA) was utilized to determine the cascades that are linked to CRIM1 in breast cancer. Finally, we explored CRIM1 and its co-expressed genes using R (3.6.3).

RESULTS

Here, we find that CRIM1 expression was downregulated in various subtypes of breast cancer, and it was lowest in triple-negative breast cancers. ER and PR status were positively correlated with CRIM1 expression, while HER-2 expression was negatively correlated with CRIM1 expression. But in our immunohistochemical results in breast cancer specimens collected from our laboratory, HER-2 expression was positively correlated with CRIM1 expression. The expression of CRIM1 was correlated with menopause status, T stage, pathologic stage, histological type, and P53 status but not with age, N-stage, M-stage, Radiation therapy, and BRCA1/2 status. Survival analysis found that low CRIM1 expression was correlated with poorer DMFS, RFS and OS. Notably, CRIM1 expression was positively linked to the level of infiltration by CD8 T-cells, endothelial cells, and neutrophils, and negatively linked to NK, B-cells, CD4 T-cells, tumor purity, macrophage M1, and Tregs. Besides, DIXDC1 and PFDN6 were correlated to CRIM1 possibly.

CONCLUSION

Our findings demonstrated that low CRIM1 expression predict poor prognosis of breast cancer and CRIM1 might be used as a possible treatment target or prognostic marker in breast cancer. More researches are needed to better understand the prognostic value of CRIM1 in breast cancer.

摘要

背景

CRIM1参与神经系统的发育和维持、毛细血管发育以及血管维持。尽管有报道称CRIM1与多种癌症有关，但其在乳腺癌中的作用尚不清楚。

方法

我们使用Oncomine、HPA和免疫组织化学分析来研究CRIM1的表达水平。利用BC-GenExMiner评估CRIM1表达与乳腺癌临床病理特征的关系。通过Kaplan-Meier分析和PrognoScan评估其与乳腺癌预后的关联。利用TIMER探索CRIM1表达与肿瘤免疫浸润的相关性。采用基因集富集分析（GSEA）来确定乳腺癌中与CRIM1相关的级联反应。最后，我们使用R（3.6.3）探索CRIM1及其共表达基因。

结果

在此，我们发现CRIM1表达在乳腺癌的各种亚型中下调，在三阴性乳腺癌中最低。雌激素受体（ER）和孕激素受体（PR）状态与CRIM1表达呈正相关，而人表皮生长因子受体2（HER-2）表达与CRIM1表达呈负相关。但在我们实验室收集的乳腺癌标本的免疫组织化学结果中，HER-2表达与CRIM1表达呈正相关。CRIM1的表达与绝经状态、T分期、病理分期、组织学类型和P53状态相关，但与年龄、N分期、M分期、放疗和BRCA1/2状态无关。生存分析发现，CRIM1低表达与较差的远处转移无进展生存期（DMFS）、无复发生存期（RFS）和总生存期（OS）相关。值得注意的是，CRIM1表达与CD8 T细胞、内皮细胞和中性粒细胞的浸润水平呈正相关，与自然杀伤细胞（NK）、B细胞、CD4 T细胞、肿瘤纯度、巨噬细胞M1和调节性T细胞（Tregs）呈负相关。此外，DIXDC1和PFDN6可能与CRIM1相关。