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线粒体丙酮酸载体 1 作为非小细胞肺癌的新型预后生物标志物。

Mitochondrial Pyruvate Carrier 1 as a Novel Prognostic Biomarker in Non-Small Cell Lung Cancer.

机构信息

Department of Oncology, the Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China.

Department of Oncology, Chongqing Beibei District Traditional Chinese Medicine Hospital, Chongqing, China.

出版信息

Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241282080. doi: 10.1177/15330338241282080.

Abstract

BACKGROUND

Abnormal mitochondrial pyruvate carrier 1 (MPC1) expression plays a key role in tumor metabolic reprogramming and progression. Understanding its significance in non-small cell lung cancer (NSCLC) is crucial for identifying therapeutic targets.

METHODS

TIMER 2.0 was utilized to assess the expression of MPC1 in both normal and cancer tissues in pan-cancer. Overall survival (OS) differences between high and low MPC1 expression were analyzed in NSCLC using the Cancer Genome Atlas (TCGA) datasets. We also examined the expression of MPC1 in NSCLC cell lines using western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). In addition, the tissue samples and clinical information of 80 patients with NSCLC from our hospital were collected. Immunohistochemistry (IHC) was used to assess MPC1 expression, and OS was evaluated using Kaplan-Meier curves and the log-rank test. Univariate and multivariate Cox regression analyses were conducted to evaluate the prognostic values of the clinical characteristics and MPC1expression

RESULTS

Analysis of public databases suggested that MPC1 was downregulated in NSCLC compared to that in normal lung tissue and predicted poor prognosis. In addition, the expression of MPC1 in NSCLC cell lines was lower than that in human bronchial epithelial (HBE) cells at both protein and mRNA levels. Further clinical analysis suggested that MPC1 expression was correlated with age, tumor T stage, and TNM stage. Kaplan-Meier analysis revealed that NSCLC patients with high MPC1 expression had a better prognosis, particularly in lung adenocarcinoma (LUAD), whereas no survival benefit was observed in lung squamous cell carcinoma (LUSC). Univariate and multivariate analyses suggested that MPC1 was an independent prognostic factor for patients with NSCLC.

CONCLUSIONS

MPC1 is poorly expressed in NSCLC, particularly in LUAD, which predicts a poor prognosis and may serve as an independent prognostic factor. Further studies on MPC1 may reveal new targets for the treatment of NSCLC.

摘要

背景

异常的线粒体丙酮酸载体 1(MPC1)表达在肿瘤代谢重编程和进展中起着关键作用。了解其在非小细胞肺癌(NSCLC)中的意义对于确定治疗靶点至关重要。

方法

使用 TIMER 2.0 评估 MPC1 在泛癌中的正常组织和癌症组织中的表达。使用癌症基因组图谱(TCGA)数据集分析 NSCLC 中高和低 MPC1 表达之间的总生存(OS)差异。我们还使用 Western blot 和定量逆转录聚合酶链反应(qRT-PCR)检测 NSCLC 细胞系中 MPC1 的表达。此外,收集了我院 80 例 NSCLC 患者的组织样本和临床资料。使用免疫组织化学(IHC)评估 MPC1 表达,使用 Kaplan-Meier 曲线和对数秩检验评估 OS。进行单因素和多因素 Cox 回归分析,以评估临床特征和 MPC1 表达的预后价值。

结果

公共数据库分析表明,与正常肺组织相比,MPC1 在 NSCLC 中下调,并预测预后不良。此外,MPC1 在 NSCLC 细胞系中的表达在蛋白质和 mRNA 水平上均低于人支气管上皮(HBE)细胞。进一步的临床分析表明,MPC1 表达与年龄、肿瘤 T 分期和 TNM 分期相关。Kaplan-Meier 分析表明,MPC1 高表达的 NSCLC 患者预后更好,尤其是在肺腺癌(LUAD)中,而在肺鳞癌(LUSC)中则没有生存获益。单因素和多因素分析表明,MPC1 是 NSCLC 患者的独立预后因素。

结论

MPC1 在 NSCLC 中表达较低,尤其是在 LUAD 中,这预示着预后不良,并且可能成为独立的预后因素。对 MPC1 的进一步研究可能会为 NSCLC 的治疗提供新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47c9/11452851/4249df7f3214/10.1177_15330338241282080-fig1.jpg

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