LAD1の発現と肺腺癌における予後的役割の探索

Lung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer (NSCLC) with a poor prognosis. To identify novel biomarkers and understand the underlying mechanisms in LUAD, we conducted a comprehensive analysis using single-cell and bulk RNA sequencing data. Our study focused on LAD1, a basement membrane filament protein that has been implicated in tumorigenesis in various cancers. We analyzed scRNA-seq data from 10 LUAD patients and identified nine cell subgroups, with LAD1 specifically expressed in cancer cells. Further analysis revealed significant correlations between LAD1 and genes associated with LUAD progression, including SFTPB, S100A6, CEACAM6, KRT19, S100A10, ANXA2, S100A11, and CAPN2. We investigated the effects of altered LAD1 expression on differentially expressed genes (DEGs), biological processes, and signaling pathways. Furthermore, we collected cancer tissue and corresponding adjacent tissue samples from 36 LUAD patients, used immunohistochemical staining to detect LAD1 expression, and analyzed its correlation with clinicopathological characteristics. We knocked down the expression of LAD1 in A549 cells using siRNA, and detected changes in LUAD cell migration and invasion ability through scratch healing assay and Transwell assay. Our results indicated diverse effects of LAD1 at both the single-cell and whole tumor levels, with a convergence on processes associated with tumor progression. In lung adenocarcinoma tissues, LAD1 was significantly upregulated, particularly in the cancer cell subgroup within tumors. Immunohistochemical results showed that LAD1 was highly expressed in LUAD, and knocking down LAD1 could inhibit LUAD cell migration and invasion. Pan-cancer analyses demonstrated LAD1 as an independent prognostic factor for overall survival in LUAD. Moreover, we developed a nomogram model incorporating LAD1 expression and clinical parameters, which demonstrated good predictive performance. The high expression of LAD1 in cancer cells, its associations with LUAD-related genes, and its links to biological processes and pathways suggest its potential biological relevance and that it merits further investigation. Overall, this study provides insights into LUAD and supports LAD1 as a gene worthy of further investigation.