基于基底膜相关基因鉴定结直肠癌分子亚型及预后特征。

IF 1.9 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Leilei Yang, Zhiqing Ji, Yufeng Ren, Chengfeng Fang, Jiaju Han, Dinghai Luo, Ruili Zhang, Shenkang Zhou
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引用次数: 0

摘要

最近的证据表明基底膜(BM)在结直肠癌(CRC)的进展中起重要作用。在这里,我们研究基于脑卒中相关基因的结直肠癌的预后价值。通过分析The Cancer Genome Atlas公共数据库和文献,获得结直肠癌中bm相关的差异表达基因(DEGs)。deg用于肿瘤样本聚类并进行生存分析。通过回归分析,构建了基于deg的CRC预后模型,并利用GEO数据集对其预测效果进行了评估和验证。评估风险评分与肿瘤进展的相关性,并结合不同临床因素采用Cox回归验证风险评分的独立性。绘制nomogram来预测结直肠癌患者的预后。采用ssGSEA和ESTIMATE分析高危组(H)和低危组(L)免疫微环境差异。计算两组患者肿瘤突变负荷(TMB)。对两组患者进行药物敏感性预测。最后,通过qPCR验证预后特征基因的表达水平。根据与肿瘤相关的deg,将CRC样本分为2类,其中第1类的存活率明显较低。基于7个基因(AGRN、TIMP1、UNC5A、SPARCL1、ADAMTS6、MMP1和UNC5C)建立预后模型。该模型具有较高的预测准确性,可作为预测结直肠癌个体预后的独立预后因素。风险评分越高,表明肿瘤进展程度越高。H组免疫浸润和TMB水平较高,提示该组个体可能更适合免疫治疗。L组获得吉西他滨和顺铂两种一线抗肿瘤药物,对个体敏感性较高。特征基因的q-PCR结果与数据库中的基因表达结果一致。本研究建立了一个7基因脑转移相关的预后模型,可用于分析结直肠癌个体的免疫景观,预测其对免疫治疗和化疗的敏感性。本研究为结直肠癌个体的预后预测及免疫治疗提供参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of colorectal cancer molecular subtypes and prognostic features based on basement membrane-related genes.

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.

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来源期刊
Journal of Applied Genetics
Journal of Applied Genetics 生物-生物工程与应用微生物
CiteScore
4.30
自引率
4.20%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The Journal of Applied Genetics is an international journal on genetics and genomics. It publishes peer-reviewed original papers, short communications (including case reports) and review articles focused on the research of applicative aspects of plant, human, animal and microbial genetics and genomics.
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