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一种用于预测结直肠癌预后的炎症相关长链非编码RNA特征

An Inflammation-Related lncRNA Signature for Prognostic Prediction in Colorectal Cancer.

作者信息

Zhang Zhenling, Luo Yingshu, Liu Yuan, Ren Jiangnan, Fang Zhaoxiong, Han Yanzhi

机构信息

Department of Gastroenterology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China.

出版信息

Cancer Rep (Hoboken). 2024 Dec;7(12):e70043. doi: 10.1002/cnr2.70043.

Abstract

BACKGROUND

Colorectal cancer (CRC) represents a commonly diagnosed malignancy affecting the digestive system. Mounting evidence shows long noncoding RNAs (lncRNAs) contribute to carcinogenesis. However, inflammation-related lncRNAs (IRLs) regulating CRC are poorly defined.

AIMS

The current study aimed to develop an IRL signature for predicting prognosis in CRC and to examine the involved molecular mechanism.

METHODS AND RESULTS

RNA-seq findings and patient data were retrieved from The Cancer Genome Atlas (TCGA), and inflammation-associated genes were obtained from the GeneCards database. IRLs with differential expression were determined with "limma" in R. Using correlation and univariable Cox analyses, prognostic IRLs were identified. The least absolute shrinkage and selection operator (LASSO) algorithm was employed to construct a prognostic model including 13 IRLs. The model's prognostic value was examined by Kaplan-Meier (K-M) survival curve and receiver operating characteristic (ROC) curve analyses. Furthermore, the association of the signature with the immune profile was assessed. Finally, RT-qPCR was carried out for verifying the expression of inflammation-related lncRNAs in nonmalignant and malignant tissue samples. A model containing 13 inflammation-related lncRNAs was built and utilized to classify cases into two risk groups based on risk score. The signature-derived risk score had a higher value in predicting survival compared with traditionally used clinicopathological properties in CRC cases. In addition, marked differences were detected in immune cells between the two groups, including CD4 T cells and M2 macrophages. Furthermore, RT-qPCR confirmed the expression patterns of these 13 lncRNAs were comparable to those of the TCGA-CRC cohort.

CONCLUSION

The proposed 13-IRL signature is a promising biomarker and may help the clinical decision-making process and improve prognostic evaluation in CRC.

摘要

背景

结直肠癌(CRC)是消化系统常见的诊断恶性肿瘤。越来越多的证据表明长链非编码RNA(lncRNAs)参与致癌过程。然而,调节CRC的炎症相关lncRNAs(IRLs)尚不明确。

目的

本研究旨在开发一种用于预测CRC预后的IRL特征,并研究其涉及的分子机制。

方法与结果

从癌症基因组图谱(TCGA)中检索RNA测序结果和患者数据,并从GeneCards数据库中获取炎症相关基因。使用R语言中的“limma”确定差异表达的IRLs。通过相关性和单变量Cox分析,鉴定出预后IRLs。采用最小绝对收缩和选择算子(LASSO)算法构建包含13个IRLs的预后模型。通过Kaplan-Meier(K-M)生存曲线和受试者工作特征(ROC)曲线分析检验该模型的预后价值。此外,评估了该特征与免疫谱的关联。最后,进行RT-qPCR以验证非恶性和恶性组织样本中炎症相关lncRNAs的表达。构建了一个包含13个炎症相关lncRNAs的模型,并根据风险评分将病例分为两个风险组。与传统使用的CRC病例临床病理特征相比,该特征衍生的风险评分在预测生存方面具有更高的价值。此外,两组之间在免疫细胞方面存在显著差异,包括CD4 T细胞和M2巨噬细胞。此外,RT-qPCR证实这13个lncRNAs的表达模式与TCGA-CRC队列的表达模式相当。

结论

所提出的13-IRL特征是一种有前景的生物标志物,可能有助于临床决策过程并改善CRC的预后评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f617/11621381/20a0f1bce227/CNR2-7-e70043-g002.jpg

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