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Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma [bulkRNA-seq]

ABSTRACT: Microscopic vascular invasion (VI) predicts recurrence and benefit from lobectomy in stage I lung adenocarcinoma (LUAD) but cannot be accurately predicted before surgery. Thus, biomarkers that identify this aggressive tumor subset are needed. Here, we show that VI in stage I LUAD is associated with reproducible gene expression programs detectable beyond the invasive focus. Using bulk RNA sequencing of 162 resected tumors and spatial transcriptomics in a subset, we identify and characterize a VI-associated gene signature. A predictor derived from this signature is associated with VI and recurrence in an independent validation cohort and is robust to intra-tumor heterogeneity in multiregional sampling data. In a cohort of pre-surgical biopsies, predictor scores correlate with matched resections and show promising discrimination of VI. These findings indicate that VI-associated transcriptional changes extend across the tumor and are detectable in limited biopsy material, supporting further validation for preoperative risk stratification in stage I LUAD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273377 | GEO | 2026/01/26

REPOSITORIES: GEO

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Project description:Background/Aims: Recurrence-free survival (RFS) following curative resection of hepatocellular carcinoma (HCC) in subjects with hepatitis C virus (HCV) infection is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized therapy. The goal of this study was to create a gene expression predictor of HCC recurrence in subjects with HCV. Methods: Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results: The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGF-beta1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions: Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression signature of the predictor gives important insights into the pathobiology of HCC recurrence and used in design of the individualized therapy. 43 tumor (JT) and 44 non-tumor (JNT) liver tissues surgically resected from patients with HCV-associated hepatocellular carcinoma; 8 non-tumor liver tissues (control samples, JC) surgically resected from HCV- or HBV-free patients with metastatic liver tumor. Inter-batch normalization was carried out using Distance Weighted Discrimination procedure. The supplementary file 'GSE17856_Readme.txt' contains a description of the replicates used for normalization. The 'GSE17856_US14702406_2514850*' files are the raw data files for the replicates.

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Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma [bulkRNA-seq]

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