单羧酸转运蛋白4（MCT4）对接受PD-1抑制剂治疗的肺腺癌患者的预测价值

The Predictive Value of Monocarboxylate Transporter 4 (MCT4) on Lung Adenocarcinoma Patients Treated with PD-1 Inhibitors.

作者信息

Zhang Qinghua, Pan Guizhen, Zhang Lu, Xu Yidan, Hao Jiqing

机构信息

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People's Republic of China.

Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People's Republic of China.

出版信息

J Inflamm Res. 2024 Dec 6;17:10515-10531. doi: 10.2147/JIR.S493632. eCollection 2024.

DOI:10.2147/JIR.S493632

PMID:39659754

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11630727/

Abstract

PURPOSE

Monocarboxylate transporter 4 (MCT4) can influence the amount of lactate in the tumor microenvironment and further control cancer cell proliferation, migration, and angiogenesis. This study aimed to evaluate the predictive value of MCT4 for prognosis and immunotherapy efficacy in advanced lung adenocarcinoma (LUAD).

PATIENTS AND METHODS

First, bioinformatics analysis was used to assess the relevance of MCT4 for survival and immunotherapy outcomes in LUAD. Subsequently, we performed a retrospective study involving 126 patients with stage IIIb to IV LUAD treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. MCT4 expression in LUAD tissues was detected by immunohistochemistry (IHC), then the patients were divided into high and low expression groups. The differences in the medical records of the two groups were compared using the X test. Kaplan-Meier (K-M) method was used for survival analysis. Univariate and multivariate analysis were used to pinpoint independent predictors, and a nomogram was developed based on the significant factors for overall survival (OS) in the multivariate analysis. The predictive ability of the nomogram was evaluated through C-index, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).

RESULTS

Both bioinformatics analysis and clinical study revealed that low MCT4 expression was associated with better prognosis and immunotherapy efficacy. Multivariate analysis of clinical characteristics showed that age >65 years, stage IV, high MCT4 expression, neutrophil-to-lymphocyte ratio (NLR)>3, lactate dehydrogenase (LDH)>250 (U/L) and carcinoembryonic antigen (CEA)>5 (ng/mL) were significantly associated with poor prognosis on immunotherapy. These factors were subsequently incorporated into the nomogram model. The C-index value of the model stood at 0.735 (95% CI= 0.662 ~ 0.807), indicating robust predictive performance of the model. The DCA curve showed that the model had a notable clinical application value.

CONCLUSION

High expression of MCT4 is associated with poor prognosis and reduced efficacy of immunotherapy in patients with advanced LUAD.

摘要

目的

单羧酸转运蛋白4（MCT4）可影响肿瘤微环境中乳酸的含量，进而控制癌细胞的增殖、迁移和血管生成。本研究旨在评估MCT4对晚期肺腺癌（LUAD）预后和免疫治疗疗效的预测价值。

患者与方法

首先，采用生物信息学分析评估MCT4与LUAD患者生存及免疫治疗结果的相关性。随后，我们进行了一项回顾性研究，纳入126例接受程序性死亡-1（PD-1）/程序性死亡配体-1（PD-L1）抑制剂治疗的Ⅲb至Ⅳ期LUAD患者。通过免疫组织化学（IHC）检测LUAD组织中MCT4的表达，然后将患者分为高表达组和低表达组。采用X检验比较两组病历的差异。采用Kaplan-Meier（K-M）法进行生存分析。采用单因素和多因素分析确定独立预测因素，并根据多因素分析中总生存（OS）的显著因素绘制列线图。通过C指数、受试者工作特征（ROC）曲线、校准曲线和决策曲线分析（DCA）评估列线图的预测能力。

结果

生物信息学分析和临床研究均显示，MCT4低表达与较好的预后和免疫治疗疗效相关。临床特征的多因素分析显示，年龄>65岁、Ⅳ期、MCT4高表达、中性粒细胞与淋巴细胞比值（NLR）>3、乳酸脱氢酶（LDH）>250（U/L）和癌胚抗原（CEA）>5（ng/mL）与免疫治疗预后不良显著相关。随后将这些因素纳入列线图模型。该模型的C指数值为0.735（95%CI = 0.662~0.807），表明该模型具有较强的预测性能。DCA曲线显示该模型具有显著的临床应用价值。