鉴定一种预测直肠癌总生存期和免疫治疗反应的线粒体自噬相关基因标记。

IF 3.4 2区 医学 Q2 ONCOLOGY
Jian Yang, Zhifei Cao, Chengqing Yu, Wenxu Cui, Jian Zhou
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引用次数: 0

摘要

背景:直肠癌是一种高度异质性的胃肠道肿瘤,治疗耐药和转移性直肠癌患者预后较差。线粒体自噬是一种针对线粒体的选择性自噬,在促进或抑制肿瘤中起作用;然而,线粒体自噬相关基因(MRGs)在直肠癌预后和治疗中的重要性尚不清楚。方法:在本研究中,我们使用来自TCGA-READ数据集的差异表达基因(deg)和mrg来鉴定差异表达的有丝分裂相关基因(mrdeg)。然后分析线粒体自噬评分的差异表达和ROC。使用加权基因共表达网络分析(WGCNA)方法鉴定了7个模块基因,并随后在合并的数据集GSE87211和GSE90627中进行了验证。根据预后特征获得模型基因,并通过风险评分区分亚组。并对基因富集、免疫浸润和免疫治疗反应进行了评价。最后,采用免疫组化(IHC)技术对临床样本进行直肠癌预后基因表达的验证。结果:我们发现22个MRGs在正常和直肠癌组织中存在差异表达。采用WGCNA和Cox回归建立了直肠癌MRGs预后模型,该模型具有较好的诊断效果。在这项研究中,我们首次确定了四种分子标记物(MYLK、FLNC、MYH11和NEXN)作为直肠癌的潜在预后生物标志物。此外,我们的研究结果表明,来自四种MRGs的风险评分与肿瘤免疫有关。为了进一步验证我们的发现,免疫组化分析表明,MYH11在直肠癌组织中的表达低于非肿瘤直肠组织。结论:磁共振成像可以预测直肠癌患者的预后和免疫治疗反应,可能为患者提供个性化治疗。
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 a mitophagy-related gene signature for predicting overall survival and response to immunotherapy in rectal cancer.

Background: Rectal cancer is a highly heterogeneous gastrointestinal tumor, and the prognosis for patients with treatment-resistant and metastatic rectal cancer remains poor. Mitophagy, a type of selective autophagy that targets mitochondria, plays a role in promoting or inhibiting tumors; however, the importance of mitophagy-related genes (MRGs) in the prognosis and treatment of rectal cancer is unclear.

Methods: In this study, we used the differentially expressed genes (DEGs) and MRGs from the TCGA-READ dataset to identify differentially expressed mitophagy-related genes (MRDEGs). The mitophagy scores were then analyzed for differential expression and ROC. Seven module genes were identified using the weighted gene coexpression network analysis (WGCNA) approach and subsequently validated in the merged datasets GSE87211 and GSE90627. The model genes were obtained based on prognostic features, and the subgroups were distinguished by risk score. Gene enrichment, immune infiltration and immunotherapy response were also evaluated. Finally, validation of prognostic gene expression in rectal cancer was carried out using clinical samples, employing Immunohistochemistry (IHC).

Results: We demonstrated that 22 MRGs were differentially expressed between normal and rectal cancer tissues. A prognostic model for rectal cancer MRGs was constructed using WGCNA and Cox regression, which exhibited good diagnostic performance. In this study, we identified four molecular markers (MYLK, FLNC, MYH11, and NEXN) as potential prognostic biomarkers for rectal cancer for the first time. Moreover, our findings indicate that the risk scores derived from the four MRGs are associated with tumor immunity. To further validate our findings, IHC analyses suggested that the expression of MYH11 in rectal cancer tissues was lower than in nontumorous rectal tissues.

Conclusion: MRGs could predict the prognosis and response to immunotherapy in patients with rectal cancer and might be able to personalize treatment for patients.

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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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