肺腺癌患者血浆中低丰度丝切蛋白-1的表达及其临床意义

doi:10.3969/j.issn.1004-616x.2025.03.005

摘要/Abstract

摘要： 目的：探讨肺腺癌患者血浆中低丰度丝切蛋白-1(cofilin-1)与肺腺癌临床病理指标及预后的关系。方法：选取24例具有完整临床信息的肺腺癌患者和52例经术后病理诊断确诊为良性肺部疾患(17例肺结核、25例炎性肉芽肿、10例错构瘤)患者。收集患者的外周血，通过试剂盒纳米磁珠对样本中的低丰度蛋白进行富集，随后进行高分辨质谱鉴定。应用目标-诱饵(TDfdr)算法在R软件中进行差异表达基因的筛选，将伪发现率控制在0.05以内。从癌症基因组图谱(TCGA)数据库中下载598例肺腺癌组织RNA表达谱和临床数据，进行Kaplan-Meier生存分析和Log-rank检验。结果：在患者血浆低丰度蛋白中，通过质谱鉴定共获得6 563个蛋白，经过TDfdr算法筛选后获得105个差异表达蛋白(其中39个在肺癌血浆样本中低表达，66个高表达)。京都基因与基因组百科全书(KEGG)分析显示，肺癌样本组低表达蛋白主要参与维持细胞的物质交换、结构稳定及正常运动功能的相关通路，这些通路参与构成了组织发育、稳态和损伤修复的分子基础。而高表达蛋白主要参与和代谢重编程、细胞分裂及运动迁移等功能相关的通路，这些通路有助于维持癌细胞的存活与生长，促进癌细胞的增殖与转移。生物信息学分析发现肌动蛋白解聚因子cofilin-1在肺腺癌患者血浆中高表达(P<0.05)，TCGA数据库中肺腺癌队列的生存分析结果显示cofilin-1高表达与患者总生存期呈负相关(r=-1.48，P<0.05)。结论：肺腺癌患者与良性肺部疾病患者血浆低丰度蛋白表达存在较大差异，cofilin-1在肺腺癌血浆和组织中高表达，且与患者不良预后相关，是一种潜在的肺腺癌血浆分子标志物。

关键词: 肺腺癌, 血浆低丰度蛋白, 蛋白质组, 丝切蛋白-1, 预后

Abstract: OBJECTIVE： To identify cofilin-1， a characteristic peripheral blood marker for recurrent metastasis of lung adenocarcinoma， by enrichment and mass spectrometry of plasma low-abundance proteins from lung adenocarcinoma patients using novel nanomaterials and to explore its relationship with clinicopathological features and prognosis of lung adenocarcinoma. METHODS： Twenty-four patients with complete clinical information of lung adenocarcinoma and 52 patients with benign lung disorders (17 tuberculosis，25 inflammatory granuloma and 10 malignant tumors) diagnosed by postoperative pathology were selected. Peripheral blood was collected from the patients，and low abundance proteins in the samples were enriched by kit nanomagnetic beads and subsequently identified by high resolution mass spectrometry. The target-decoy (TDfdr) algorithm was applied to screen differentially expressed genes in R software to control the pseudo-discovery rate within 0.05. RNA expression profiles and clinical data of 598 lung adenocarcinoma tissues were downloaded from The Cancer Genome Atlas (TCGA) database for Kaplan-Meier survival analysis and Log-rank test. RESULTS： A total of 6 563 proteins were identified by mass spectrometry， and 105 differentially expressed proteins were obtained after screening by the TDfdr algorithm (39 of which were lowly expressed and 66 were highly expressed in lung cancer plasma samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the low-expressed proteins were mainly involved in pathways related to the maintenance of the cell's material exchange，structural stability，and normal motor functions，which are involved in constituting the molecular basis of tissue development， homeostasis， and damage repair. On the other hand， the highly expressed proteins were mainly involved in pathways related to metabolic reprogramming，cell division，and motor migration，which help to maintain the survival and growth of cancer cells and promote the proliferation and metastasis of cancer cells. Bioinformatics analysis revealed that the actin depolymerization factor cofilin-1 was highly expressed in the plasma of lung adenocarcinoma patients (P<0.05)， and the high expression of cofilin-1 in TCGA lung adenocarcinoma tissues was negatively correlated with the overall survival of the patients (r=-1.48，P<0.05). CONCLUSION： There are large differences in plasma low abundance protein expression between patients with lung adenocarcinoma and those with benign lung diseases. High expression of cofilin-1 in cancer plasma and tissue correlated with poor prognosis of the patients，and it may therefore be useful as a plasma molecular marker for lung adenocarcinoma.

Key words: lung adenocarcinoma, plasma low-abundance proteins, proteome, cofilin-1, prognosis

中图分类号:

R734.2

季杰, 马晟, 黄桂汶, 肖汀. 肺腺癌患者血浆中低丰度丝切蛋白-1的表达及其临床意义[J]. 癌变·畸变·突变, 2025, 37(3): 202-208.

JI Jie, MA Sheng, HUANG Guiwen, XIAO Ting. Expression and clinical significance of marker cofilin-1 in low-abundance proteome from plasma of lung adenocarcinoma patients[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(3): 202-208.

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