全面鉴定与迁移体相关的长链非编码RNA特征以预测结肠腺癌的预后和治疗方案。

Comprehensive identification of a migrasomes-associated long non-coding RNA signature to predict the prognosis and treatment options in colon adenocarcinoma.

作者信息

Zheng Zhen, Liu Hui, Xu Quan, Cui Wei, Liu Kaitai

机构信息

Department of Chemoradiation Oncology, The Affiliated Lihuili Hospital of Ningbo University, 57 Xingning Road, Ningbo, 315000, Zhejiang, China.

Department of Colorectal Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, China.

出版信息

Discov Oncol. 2025 Mar 27;16(1):409. doi: 10.1007/s12672-025-02197-9.

DOI:10.1007/s12672-025-02197-9

PMID:40146487

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11950624/

Abstract

BACKGROUND

Migrasomes, recently discovered cellular substructures, may play a crucial role in cancer progression, treatment response, and prognosis. However, the prognostic value of migrasome-associated long non-coding RNAs (lncRNAs) in colon adenocarcinoma (COAD) remains unexplored.

METHODS

RNA-seq data from 459 COAD patients, including clinical characteristics and outcome information, were obtained from The Cancer Genome Atlas. A risk model was constructed through co-expression analysis of migrasome genes and lncRNAs, followed by Cox regression and least absolute shrinkage and selection operator analysis to identify prognostic lncRNAs. Functional enrichment analyses were performed to elucidate underlying biological mechanisms. Immune landscape characterization utilized ESTIMATE, CIBERSORT, Tumor Immune Estimation Resource (TIME), and single-sample Gene Set Enrichment Analysis (ssGSEA). Drug sensitivity analysis was conducted for select therapeutic agents.

RESULTS

Nine prognostic lncRNAs (AC010463.3, AL590483.4, AP005264.1, ZEB1-AS1, AC104088.1, PRKAR1B-AS2, AC009315.1, SUCLG2-AS1, and AC006111.2) were identified and incorporated into a risk model. Low-risk patients demonstrated significantly improved survival outcomes. The model exhibited independent prognostic capability, with AUCs of 0.783, 0.749, and 0.713 for one-, three-, and five-year survival, respectively, in the training cohort. High-risk patients displayed reduced overall survival and elevated tumor mutation burden. Additionally, these patients showed decreased sensitivity to therapeutic agents, including Oxaliplatin, Irinotecan, and 5-Fluorouracil.

CONCLUSION

Our novel migrasome-associated lncRNA signature demonstrates robust predictive capacity for both prognosis and chemotherapeutic sensitivity in COAD, potentially facilitating personalized treatment strategies and improved patient management.

摘要

背景

迁移小体是最近发现的细胞亚结构，可能在癌症进展、治疗反应和预后中起关键作用。然而，迁移小体相关长链非编码RNA（lncRNA）在结肠腺癌（COAD）中的预后价值仍未得到探索。

方法

从癌症基因组图谱获取了459例COAD患者的RNA测序数据，包括临床特征和结局信息。通过迁移小体基因和lncRNA的共表达分析构建风险模型，随后进行Cox回归以及最小绝对收缩和选择算子分析以鉴定预后lncRNA。进行功能富集分析以阐明潜在的生物学机制。利用ESTIMATE、CIBERSORT、肿瘤免疫估计资源（TIME）和单样本基因集富集分析（ssGSEA）对免疫景观进行表征。对选定的治疗药物进行药物敏感性分析。

结果

鉴定出9种预后lncRNA（AC010463.3、AL590483.4、AP005264.1、ZEB1-AS1、AC104088.1、PRKAR1B-AS2、AC009315.1、SUCLG2-AS1和AC006111.2）并将其纳入风险模型。低风险患者的生存结局显著改善。该模型具有独立的预后能力，在训练队列中，1年、3年和5年生存的受试者工作特征曲线下面积（AUC）分别为0.783、0.749和0.713。高风险患者的总生存期缩短，肿瘤突变负担增加。此外，这些患者对包括奥沙利铂、伊立替康和5-氟尿嘧啶在内的治疗药物的敏感性降低。