MTHFD1L is a novel prognostic marker and therapeutic target in cutaneous melanoma.

IF 2.4 3区医学 Q2 PATHOLOGY

Diagnostic Pathology Pub Date : 2025-07-10 DOI:10.1186/s13000-025-01680-9

Xinlian Xie, Guangfu Shi, Kebin Ning, Zhenjie Wu

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引用次数: 0

Abstract

Background: Skin cutaneous melanoma (SKCM) is one of the highly malignant tumor. This study aimed to investigate the expression levels of MTHFD1L in cutaneous melanoma and to uncover its potential biological significance.

Methods: This investigation employed the TCGA-SKCM dataset along with combined GSE15605 and GSE19234 datasets to analyze MTHFD1L expression patterns. Comprehensive bioinformatics analyses were conducted, including GO and KEGG pathway enrichment analyses, protein-protein interaction network construction, and evaluation of the relationship between MTHFD1L expression and immune infiltration. Prognostic significance was assessed using the GEPIA2 database. Experimental validation involved: (1) RT-qPCR, Western blot, and IHC staining to compare MTHFD1L expression between SKCM and normal tissues; (2) establishment of MTHFD1L knockdown models in A375 and 2058 cell lines for functional characterization.

Results: The MTHFD1L level was increasing in SKCM tissues from GSE15605/GSE19234 and TCGA-SKCM, and high MTHFD1L expression correlated with poor overall survival. The RT-qPCR, Western blot and IHC confirmed the accuracy of bioinformatics. Knockdown of MTHFD1L significantly inhibited proliferation, migration, invasion, and clonogenic ability in A375 and A2058 melanoma cells, potentially through regulation of the TGF-β/SMAD signaling pathway.

Conclusion: MTHFD1L is a potential biomarker in cutaneous melanoma, and could potentially serve as a therapeutic target for SKCM.

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MTHFD1L是一种新的皮肤黑色素瘤预后标志物和治疗靶点。

背景：皮肤黑色素瘤（Skin Skin melanoma， SKCM）是恶性肿瘤之一。本研究旨在探讨MTHFD1L在皮肤黑色素瘤中的表达水平，并揭示其潜在的生物学意义。方法：采用TCGA-SKCM数据集，结合GSE15605和GSE19234数据集，分析MTHFD1L的表达模式。我们进行了全面的生物信息学分析，包括GO和KEGG通路富集分析、蛋白-蛋白相互作用网络构建、MTHFD1L表达与免疫浸润的关系评价。使用GEPIA2数据库评估预后意义。实验验证包括：(1)RT-qPCR、Western blot、IHC染色比较SKCM与正常组织中MTHFD1L的表达；(2)在A375和2058细胞系中建立MTHFD1L敲低模型进行功能表征。结果：GSE15605/GSE19234和TCGA-SKCM组SKCM组织中MTHFD1L表达水平升高，MTHFD1L高表达与总生存期差相关。RT-qPCR、Western blot和免疫组化证实了生物信息学的准确性。敲低MTHFD1L可显著抑制A375和A2058黑色素瘤细胞的增殖、迁移、侵袭和克隆生成能力，可能是通过调控TGF-β/SMAD信号通路实现的。结论：MTHFD1L是皮肤黑色素瘤的潜在生物标志物，可能作为SKCM的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diagnostic Pathology 医学-病理学

CiteScore

4.60

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Diagnostic Pathology is an open access, peer-reviewed, online journal that considers research in surgical and clinical pathology, immunology, and biology, with a special focus on cutting-edge approaches in diagnostic pathology and tissue-based therapy. The journal covers all aspects of surgical pathology, including classic diagnostic pathology, prognosis-related diagnosis (tumor stages, prognosis markers, such as MIB-percentage, hormone receptors, etc.), and therapy-related findings. The journal also focuses on the technological aspects of pathology, including molecular biology techniques, morphometry aspects (stereology, DNA analysis, syntactic structure analysis), communication aspects (telecommunication, virtual microscopy, virtual pathology institutions, etc.), and electronic education and quality assurance (for example interactive publication, on-line references with automated updating, etc.).