CSRP1 表达与结直肠癌中富含间质的间充质肿瘤特征和不良预后相关。
CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer.
机构信息
Division of Tumor Pathology, Department of Clinical Oncology, Cancer Institute, Hacettepe University, Ankara, Turkiye.
出版信息
Turk J Med Sci. 2023 Oct 31;53(6):1678-1689. doi: 10.55730/1300-0144.5736. eCollection 2023.
BACKGROUND/AIM: Cysteine and glycine-rich protein 1 (CSRP1) is involved in the cysteine-rich protein family and is a marker of smooth muscle lineages. In colon cancer, the expression of this gene is associated with poor prognosis. In this study, the aim was to reevaluate its prognostic relationship in independent cohorts and explore potential underlying biological processes that are linked to aggressive behavior in tumors with high CSRP1 expression, such as epithelial-to-mesenchymal transition (EMT), stromal fractions in the tumor microenvironment, and consensus molecular subtypes (CMSs).
MATERIALS AND METHODS
RNA sequencing (RNAseq)-, microarray-, and single-cell RNAseq (scRNAseq)-based transcriptomic data were obtained from public databases. The EMT score was calculated based on the expression of E-cadherin and vimentin genes using a previously published method. The stromal score generated by the ESTIMATE method was utilized for the analysis of correlation with the CSRP1 expression. The scRNAseq data were analyzed via the Seurat R package. The immunohistochemistry-based protein level expression of CSRP1 was evaluated using the Human Protein Atlas database.
RESULTS
Lower CSRP1 expression was noted in colon tumors compared to normal colon tissue. Patients with a high CSRP1 expression had shorter recurrence-free, overall, and disease-specific survivals in the GSE39582 and GSE17536 datasets (p < 0.05). The methylation level of the CSRP1 gene was negatively correlated (r = -0.57, p < 0.0001) with CSRP1 expression in The Cancer Genome Atlas colon adenocarcinoma dataset. CSRP1 expression was positively correlated with the expression of mesenchymal markers, EMT score, and stromal score obtained via the ESTIMATE method. CMS4 colon tumors had a significantly higher CSRP1 expression compared to other CMSs. Analysis of the scRNAseq data revealed that CSRP1 was expressed by epithelial cells and cancer-associated fibroblasts in the colorectal tumor microenvironment, which was also confirmed by the protein expression data from the Human Protein Atlas database.
CONCLUSION
CSRP1 expression is associated with CMS4, a more mesenchymal stroma-rich molecular profile, and poor prognosis in colon cancer.
背景/目的：富含半胱氨酸和甘氨酸蛋白 1（CSRP1）属于富含半胱氨酸蛋白家族，是平滑肌谱系的标志物。在结肠癌中，该基因的表达与预后不良相关。本研究旨在重新评估其在独立队列中的预后相关性，并探索与高 CSRP1 表达肿瘤侵袭性行为相关的潜在生物学过程，如上皮-间充质转化（EMT）、肿瘤微环境中的基质分数以及共识分子亚型（CMS）。
材料和方法
从公共数据库中获取基于 RNA 测序（RNAseq）、微阵列和单细胞 RNAseq（scRNAseq）的转录组数据。使用先前发表的方法，根据 E-钙黏蛋白和波形蛋白基因的表达计算 EMT 评分。利用 ESTIMATE 方法生成的基质评分用于分析与 CSRP1 表达的相关性。通过 Seurat R 包分析 scRNAseq 数据。使用人类蛋白质图谱数据库评估 CSRP1 的基于免疫组织化学的蛋白水平表达。
结果
与正常结肠组织相比，结肠肿瘤中 CSRP1 的表达较低。在 GSE39582 和 GSE17536 数据集（p<0.05）中，CSRP1 高表达的患者无复发生存期、总生存期和疾病特异性生存期更短。在癌症基因组图谱结肠腺癌数据集中，CSRP1 基因的甲基化水平与 CSRP1 表达呈负相关（r=-0.57，p<0.0001）。CSRP1 表达与 ESTIMATE 方法获得的间充质标志物、EMT 评分和基质评分呈正相关。与其他 CMS 相比，CMS4 结肠肿瘤的 CSRP1 表达显著更高。对 scRNAseq 数据的分析表明，CSRP1 由结直肠肿瘤微环境中的上皮细胞和癌症相关成纤维细胞表达，这也得到了人类蛋白质图谱数据库中蛋白表达数据的证实。
结论
CSRP1 表达与 CMS4 相关，CMS4 是一种富含间充质基质的分子特征，与结肠癌的预后不良相关。
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