Sarang Sanjan S, Cahill Catherine M, Rogers Jack T
Neurochemistry Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Biomolecules. 2025 May 31;15(6):803. doi: 10.3390/biom15060803.
Lung cancer is responsible for 2.21 million annual cancer cases and is the leading worldwide cause of cancer-related deaths. Specifically, lung adenocarcinoma (LUAD) is the most prevalent lung cancer subtype resulting from genetic causes; LUAD has a 15% patient survival rate due to it commonly being detected in its advanced stages. This study aimed to identify a novel biomarker signature of early-stage LUAD utilizing gene expression analysis of human lung tissue samples. Using 22 pairs of LUAD and matched normal lung microarrays, 229 differentially expressed genes were identified. These genes were networked for their protein-protein interactions, and 44 hub genes were determined from protein essentiality. Survival analysis of 478 LUAD patient samples identified four statistically significant candidates. These candidate genes' expression profiles were validated from GTEx and TCGA (347 normal, 483 LUAD samples); immunohistochemistry validated the subsequent protein presence. Through intensive bioinformatic identification and multiple validations of the four-biomarker gene signature, AGER, MGP, and PECAM1 were identified as downregulated in LUAD; SLC2A1 was identified as upregulated in LUAD. These four biologically significant genes are involved in tumorigenesis and poor LUAD prognosis, meriting their use as a clinical biomarker signature and therapeutic targets for early-stage LUAD.
肺癌每年导致221万例癌症病例，是全球癌症相关死亡的主要原因。具体而言，肺腺癌（LUAD）是由遗传原因导致的最常见的肺癌亚型；由于LUAD通常在晚期被检测到，其患者生存率为15%。本研究旨在通过对人肺组织样本进行基因表达分析，确定早期LUAD的一种新型生物标志物特征。利用22对LUAD和匹配的正常肺微阵列，鉴定出229个差异表达基因。这些基因通过蛋白质-蛋白质相互作用形成网络，并根据蛋白质必需性确定了44个中心基因。对478例LUAD患者样本进行生存分析，确定了四个具有统计学意义的候选基因。这些候选基因的表达谱在GTEx和TCGA（347例正常样本、483例LUAD样本）中得到验证；免疫组织化学验证了随后蛋白质的存在。通过对四生物标志物基因特征进行深入的生物信息学鉴定和多次验证，发现AGER、MGP和PECAM1在LUAD中表达下调；SLC2A1在LUAD中表达上调。这四个具有生物学意义的基因参与肿瘤发生和LUAD预后不良，值得用作早期LUAD的临床生物标志物特征和治疗靶点。
