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基于基底膜相关基因的结直肠癌分子亚型鉴定及预后特征分析

Identification of colorectal cancer molecular subtypes and prognostic features based on basement membrane-related genes.

作者信息

Yang Leilei, Ji Zhiqing, Ren Yufeng, Fang Chengfeng, Han Jiaju, Luo Dinghai, Zhang Ruili, Zhou Shenkang

机构信息

Department of Gastrointestinal Surgery, Taizhou Hospital, Wenzhou Medical University, Linhai, Zhejiang, China.

Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, 150 West Gate Street, Linhai, Zhejiang, China.

出版信息

J Appl Genet. 2025 Aug 2. doi: 10.1007/s13353-025-00992-2.

Abstract

Recent evidence suggests that the basement membrane (BM) plays an important role in the progression of colorectal cancer (CRC). Here, we investigate the prognostic value of CRC based on BM-associated genes. BM-related differentially expressed genes (DEGs) in CRC were obtained through analysis of The Cancer Genome Atlas public database and literature. The DEGs were used to cluster tumor samples and perform survival analysis. A prognostic model was constructed based on the DEGs in CRC through regression analysis, and its predictive effect was evaluated and validated using the GEO dataset. The correlation between riskscore and tumor progression was evaluated, and Cox regression was used to verify the independence of riskscore by combining it with different clinical factors. A nomogram was drawn to predict the prognosis of CRC individuals. The differences in immune microenvironment between high-risk (H) and low-risk (L) groups were analyzed by ssGSEA and ESTIMATE. The tumor mutation burden (TMB) was calculated for the two groups. Drug sensitivity prediction was performed for the two groups. Finally, the expression levels of prognostic feature genes were validated through qPCR. Based on BM-related DEGs, CRC samples were classified into 2 clusters, with cluster 1 having significantly lower survival rates. A prognostic model was developed based on 7 genes (AGRN, TIMP1, UNC5A, SPARCL1, ADAMTS6, MMP1, and UNC5C). The model exhibited high predictive accuracy and demonstrated the potential to serve as an independent prognostic factor for predicting the prognosis of CRC individuals. A higher riskscore indicated a higher degree of tumor progression. Group H demonstrated higher levels of immune infiltration and TMB, suggesting that individuals in this group might be more suitable for immune therapy. Two first-line anti-tumor drugs, Gemcitabine and Cisplatin, with higher sensitivity to individuals in group L were obtained. The q-PCR results of the feature genes were consistent with the results of gene expression in the database. This study established a 7-gene BM-related prognostic model that could be used to analyze the immune landscape of CRC individuals and predict their sensitivity to immunotherapy and chemotherapy. This research provided a reference for the prognosis prediction and immunotherapy of CRC individuals.

摘要

近期证据表明,基底膜(BM)在结直肠癌(CRC)进展中起重要作用。在此,我们基于与BM相关的基因研究CRC的预后价值。通过分析癌症基因组图谱公共数据库和文献,获取CRC中与BM相关的差异表达基因(DEG)。利用这些DEG对肿瘤样本进行聚类并进行生存分析。通过回归分析基于CRC中的DEG构建预后模型,并使用GEO数据集评估和验证其预测效果。评估风险评分与肿瘤进展之间的相关性,并通过将其与不同临床因素相结合,使用Cox回归验证风险评分的独立性。绘制列线图以预测CRC个体的预后。通过单样本基因集富集分析(ssGSEA)和ESTIMATE分析高风险(H)和低风险(L)组之间免疫微环境的差异。计算两组的肿瘤突变负荷(TMB)。对两组进行药物敏感性预测。最后,通过定量聚合酶链反应(qPCR)验证预后特征基因的表达水平。基于与BM相关的DEG,将CRC样本分为2个聚类,聚类1的生存率显著较低。基于7个基因(AGRN、TIMP1、UNC5A、SPARCL1、ADAMTS6、MMP1和UNC5C)开发了一种预后模型。该模型具有较高的预测准确性,并显示出作为预测CRC个体预后的独立预后因素的潜力。较高的风险评分表明肿瘤进展程度较高。H组显示出更高水平的免疫浸润和TMB,表明该组个体可能更适合免疫治疗。获得了对L组个体敏感性较高的两种一线抗肿瘤药物吉西他滨和顺铂。特征基因的q-PCR结果与数据库中的基因表达结果一致。本研究建立了一种与BM相关的7基因预后模型,可用于分析CRC个体的免疫格局,并预测其对免疫治疗和化疗的敏感性。本研究为CRC个体的预后预测和免疫治疗提供了参考。

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