Wang Xiao, Lu Yanwei, Liu Ruiqi, Huang Luanluan, Xu Keke, Xiong Hao, Nan Ding, Shou Yiyi, Sheng Hailong, Zhang Haibo, Wang Xian, Chen Xiaoyan
Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Medical Oncology, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Sci Rep. 2025 May 22;15(1):17873. doi: 10.1038/s41598-025-03153-x.
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.
由于缺乏可靠的生物标志物，癌症死亡率不断上升，这凸显了对先进诊断和预后策略的迫切需求。本研究调查了LZTS2作为一种泛癌生物标志物的作用，强调其对免疫治疗和治疗靶点的预测价值。与现有的生物标志物如肝细胞癌中的甲胎蛋白（AFP）或胃癌中的人表皮生长因子受体2（HER2）不同，后者具有组织特异性效用，LZTS2表现出独特的跨癌适用性，这在肝细胞癌（LIHC）和胃腺癌（STAD）中其一致的失调以及与其他恶性肿瘤的新关联中得到了证明。利用包括UALCAN、KM-plotter和癌症基因组图谱（TCGA）在内的先进生物信息学工具和数据库，以及在LIHC和STAD细胞系中的实验验证，我们分析了LZTS2的表达模式及其临床相关性。值得注意的是，LZTS2的双重作用——在某些癌症中作为肿瘤抑制因子，而在其他癌症中促进肿瘤发生——使其有别于传统的单功能标志物，为其调节多功能性提供了新的见解。我们的研究结果表明，LZTS2突变和表达水平与癌症进展和患者生存密切相关，巩固了其作为预后生物标志物的潜力。值得注意的是，LZTS2表达与各种临床病理参数相关，突出了其在癌症生物学中的重要性。通路分析突出了LZTS2参与关键生物学过程，为治疗干预提供了可操作的见解。定量实时聚合酶链反应（qRT-PCR）和定量甲基化特异性PCR（qMSP）实验验证证实了这些结果，进一步确立了LZTS2作为整合遗传、表观遗传和免疫特征的多维生物标志物的效用——这一能力在现有标志物中很少见。这种全面分析将LZTS2定位为癌症进展中的关键角色，为加强临床管理开辟了有前景的途径。
