基于综合计算生物学和实验验证鉴定脑胶质瘤的稳健生物标志物 LAPTM4A。

Identification of a robust biomarker LAPTM4A for glioma based on comprehensive computational biology and experimental verification.

机构信息

Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.

Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.

出版信息

Aging (Albany NY). 2024 Apr 12;16(8):6954-6989. doi: 10.18632/aging.205736.

DOI:10.18632/aging.205736

PMID:38613802

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11087115/

Abstract

BACKGROUND

Glioma, a highly invasive and deadly form of human neoplasm, presents a pressing need for the exploration of potential therapeutic targets. While the lysosomal protein transmembrane 4A (LATPM4A) has been identified as a risk factor in pancreatic cancer patients, its role in glioma remains unexplored.

METHODS

The analysis of differentially expressed genes (DEG) was conducted from The Cancer Genome Atlas (TCGA) glioma dataset and the Genotype Tissue Expression (GTEx) dataset. Through weighted gene co-expression network analysis (WGCNA), the key glioma-related genes were identified. Among these, by using Kaplan-Meier (KM) analysis and univariate/multivariate COX methods, LAPTM4A emerged as the most influential gene. Moreover, the bioinformatics methods and experimental verification were employed to analyze its relationships with diagnosis, clinical parameters, epithelial-mesenchymal transition (EMT), metastasis, immune cell infiltration, immunotherapy, drug sensitivity, and ceRNA network.

RESULTS

Our findings revealed that LAPTM4A was up-regulated in gliomas and was associated with clinicopathological features, leading to poor prognosis. Furthermore, functional enrichment analysis demonstrated that LATPM4A played a role in the immune system and cancer progression. experiments indicated that LAPTM4A may influence metastasis through the EMT pathway in glioma. Additionally, we found that LAPTM4A was associated with the tumor microenvironment (TME) and immunotherapy. Notably, drug sensitivity analysis revealed that patients with high LAPTM4A expression were sensitive to doxorubicin, which contributed to a reduction in LAPTM4A expression. Finally, we uncovered the FGD5-AS1-hsa-miR-103a-3p-LAPTM4A axis as a facilitator of glioma progression.

CONCLUSIONS

In conclusion, our study identifies LATPM4A as a promising biomarker for prognosis and immune characteristics in glioma.

摘要

背景

神经胶质瘤是一种具有高度侵袭性和致命性的人类肿瘤，因此迫切需要探索潜在的治疗靶点。虽然溶酶体蛋白跨膜 4A（LATPM4A）已被确定为胰腺癌患者的风险因素，但它在神经胶质瘤中的作用尚未得到探索。

方法

从癌症基因组图谱（TCGA）神经胶质瘤数据集和基因型组织表达（GTEx）数据集分析差异表达基因（DEG）。通过加权基因共表达网络分析（WGCNA），确定关键的神经胶质瘤相关基因。其中，通过Kaplan-Meier（KM）分析和单变量/多变量 COX 方法，LAPTM4A 作为最具影响力的基因脱颖而出。此外，还运用生物信息学方法和实验验证分析了 LAPTM4A 与诊断、临床参数、上皮间质转化（EMT）、转移、免疫细胞浸润、免疫治疗、药物敏感性和 ceRNA 网络的关系。

结果

我们的研究结果表明，LAPTM4A 在神经胶质瘤中上调，并与临床病理特征相关，导致预后不良。此外，功能富集分析表明 LATPM4A 在免疫系统和癌症进展中发挥作用。实验表明，LAPTM4A 可能通过 EMT 通路影响神经胶质瘤的转移。此外，我们发现 LAPTM4A 与肿瘤微环境（TME）和免疫治疗有关。值得注意的是，药物敏感性分析表明，高表达 LAPTM4A 的患者对阿霉素敏感，这有助于降低 LAPTM4A 的表达。最后，我们揭示了 FGD5-AS1-hsa-miR-103a-3p-LAPTM4A 轴作为神经胶质瘤进展的促进因子。