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肺癌中的线粒体 DNA:从生物学到临床意义

英文原题:Mitochondrial DNA in lung cancer: From biology to clinical implications.

PubMed 2026/06/18(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

研究概要

这些新出现的发现表明,mtDNA分析是肺癌精准肿瘤学中一种有价值的补充方法。

中文摘要

线粒体DNA(mtDNA)正在成为非小细胞肺癌(NSCLC)分子图谱中的一个相关组成部分。由于其固有的对环境致癌物的易感性,线粒体基因组积累改变——如D-loop和电子传递链变异——这些改变日益被认为是肿瘤发展和代谢转变的潜在介质。近期研究结果凸显了mtDNA的潜在临床应用。在诊断方面,基于cf-mtDNA片段组学和tRNA衍生片段的新兴模型已显示出用于早期诊断的良好前景。在预后方面,复合物I中的体细胞变异和特定的线粒体lncRNA特征已被评估为总生存期和转移风险的独立指标。此外,线粒体质量可能有助于化疗方案的选择。另外,线粒体向TIL(肿瘤浸润淋巴细胞)的水平转移为理解免疫治疗耐药提供了新的框架。尽管这些初步结果为分子分层提供了有前景的路线图,但将其整合到常规实践中仍是一个目标,需要在更大规模、多种族队列中进行进一步的前瞻性验证,以确保可重复性并区分功能性驱动变异与伴随变异。总体而言,这些新兴发现表明,mtDNA分析代表了肺癌精准肿瘤学中一种有价值的补充方法。

展开英文摘要原文

Mitochondrial DNA (mtDNA) is emerging as a relevant component of the molecular landscape in non-small cell lung cancer (NSCLC). Due to its inherent vulnerability to environmental carcinogens, the mitochondrial genome accumulates alterations-such as D-loop and Electron Transport Chain variants- increasingly identified as potential mediators of tumor development and metabolic shifts. Recent findings highlight potential clinical applications of mtDNA. In diagnostics, emerging models based on cf-mtDNA fragmentomics and tRNA-derived fragments have shown promising capabilities for early-stage diagnosis. Prognostically, somatic variants in Complex I and specific mitochondrial lncRNA signatures have been evaluated as independent indicators of overall survival and metastatic risk. Furthermore, mitochondrial mass may potentially support chemotherapy election. Additionally, horizontal transfer of mitochondria to tumor-infiltrating lymphocytes offers a novel framework for understanding resistance to immunotherapy. While these preliminary results provide a promising roadmap for molecular stratification, their integration into routine practice remains a goal that requires further prospective validation in larger, multi-ethnic cohorts to ensure reproducibility and to distinguish functional drivers from passenger variants. Collectively, these emerging findings suggest that mtDNA analysis represents a valuable complementary approach to precision oncology in lung cancer.

论文信息

作者
Lucio-Lozada J、Prada D、Beato-González L、Hirsch FR、Cardona AF、Hernández-Pedro N、Arrieta O
第一作者单位
Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), San Fernando No. 22, Col. Sección 16, C.P. 14080, Mexico City, Mexico. Electronic address: josemarialuciounam@gmail.com.Mexico
通讯作者单位
Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), San Fernando No. 22, Col. Sección 16, C.P. 14080, Mexico City, Mexico; Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), San Fernando No. 22, Col. Sección 16, C.P. 14080, Mexico City, Mexico. Electronic address: oarrieta@incan.edu.mx.Mexico
文献类型
综述
期刊
Critical reviews in oncology/hematology2026 Oct
原文标识
PubMed 42314881 · DOI 10.1016/j.critrevonc.2026.105431