Journal Article

LZTS2 methylation as a potential diagnostic and prognostic marker in LIHC and STAD: Evidence from bioinformatics and in vitro analyses

Chen, Xiaoyan, Liu, Ruiqi, Xiong, Hao, Huang, Luanluan, Shou, Yiyi, Xu, Keke, Lu, Yanwei, Sheng, Hailong, Nan, Ding, Wang, Xian, Wang, Xiao, Zhang, Haibo

2025

Overview

The rising mortality rate from cancer, driven by the absence of reliable biomarkers, highlights the pressing need for advanced diagnostic and prognostic strategies. This study investigates LZTS2’s role as a pan-cancer biomarker, emphasizing its predictive value for immunotherapy and therapeutic targeting. Unlike existing biomarkers such as AFP in hepatocellular carcinoma or HER2 in gastric cancer, which exhibit tissue-specific utility, LZTS2 demonstrates unique cross-cancer applicability, as evidenced by its consistent dysregulation in both liver hepatocellular carcinoma (LIHC) and stomach adenocarcinoma (STAD) alongside emerging associations with other malignancies. Leveraging advanced bioinformatics tools and databases including UALCAN, KM-plotter, and The Cancer Genome Atlas (TCGA), alongside experimental validation in LIHC and STAD cell lines, we analyze LZTS2 expression patterns and their clinical relevance. Notably, LZTS2’s dual role—acting as a tumor suppressor in some cancers while promoting oncogenesis in others—distinguishes it from conventional single-function markers, offering novel insights into its regulatory versatility. Our findings reveal that LZTS2 mutations and expression levels are closely associated with cancer progression and patient survival, solidifying its potential as a prognostic biomarker. Notably, LZTS2 expression correlates with various clinicopathological parameters, underscoring its significance in cancer biology. Pathway analysis highlights LZTS2’s involvement in critical biological processes, providing actionable insights for therapeutic interventions. Quantitative real-time polymerase chain reaction (qRT-PCR) and quantitative methylation-specific PCR (qMSP) experimental validations confirm these results, further establishing LZTS2’s utility as a multi-dimensional biomarker that integrates genetic, epigenetic, and immunological features—a capability rarely observed in existing markers. This comprehensive analysis positions LZTS2 as a pivotal player in cancer progression, opening promising avenues for enhanced clinical management.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/337 / 631/67 / Adenocarcinoma / Adenocarcinoma - diagnosis / Adenocarcinoma - genetics / Adenocarcinoma - metabolism / Adenocarcinoma - pathology / Bioinformatics / Biomarkers / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Cancer / Carcinoma, Hepatocellular - diagnosis / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - metabolism / Carcinoma, Hepatocellular - mortality / Carcinoma, Hepatocellular - pathology / Cell Line, Tumor / Computational Biology - methods / DNA Methylation / Epigenetics / ErbB-2 protein / Gastric cancer / Gene Expression Regulation, Neoplastic / Hepatocellular carcinoma / Humanities and Social Sciences / Humans / Immunotherapy / Liver cancer / Liver Neoplasms - diagnosis / Liver Neoplasms - genetics / Liver Neoplasms - metabolism / Liver Neoplasms - mortality / Liver Neoplasms - pathology / LZTS2 / Malignancy / Metastasis / Methylation / multidisciplinary / Neoplasm / Polymerase chain reaction / Prognosis / qMSP / Science / Science (multidisciplinary) / Stomach Neoplasms - diagnosis / Stomach Neoplasms - genetics / Stomach Neoplasms - metabolism / Stomach Neoplasms - mortality / Stomach Neoplasms - pathology / Therapeutic applications / Therapeutic targets / Tumor suppressor genes / Tumor Suppressor Proteins - genetics / Tumor Suppressor Proteins - metabolism / Tumorigenesis