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September 1st, 2025
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Nucleo de Pesquisas em Oncologia, Federal University of Para, Belem, PA, Brazil
genomics
bioRxiv

EXPRESSION INSIGHTS INTO GASTRIC ADENOCARCINOMA: NETWORK ANALYSIS REVEALS KEY HUB GENES AND FUNCTIONAL MODULES

Mourao, R. M. d. S.Open in Google Scholar•Moreira, F. C.Open in Google Scholar•da Silva, J. M. C.Open in Google Scholar•da Costa, D. d. S. A.Open in Google Scholar•da Silva, V. C. S.Open in Google Scholar•Vidal, A. F.Open in Google Scholar•Magalhaes, L. L. d.Open in Google Scholar•Anaissi, A. K. M.Open in Google Scholar•Demachki, S.Open in Google Scholar•Barra, W. F.Open in Google Scholaret al.

Gastric cancer remains a leading cause of cancer-related mortality worldwide, with poor survival rates. To uncover its molecular basis, we performed weighted gene coexpression network analysis on RNA-seq data from 119 gastric adenocarcinoma (GAC) and peritumoral tissue (PTT) samples. We identified six key coexpression modules: MEmagenta, MEbrown, MEgreen, and MEturquoise showed strong positive correlations with GAC, whereas MEblack and MEblue were negatively correlated. Hub genes such as COL3A1, PGAM1, and CFL1 were among the most highly expressed in GAC samples compared to PTT. ROC analyses of selected hub genes yielded AUC values exceeding 0.80 for distinguishing GAC from PTT, underscoring their diagnostic potential. Integrating cellular deconvolution with module expression revealed that MEblack hub genes (TFF1, TFF2, GKN1, GKN2 and MUCL3) correlated positively with B-cell abundance and negatively with resting mast cells and neutrophils. Conversely, MEturquoise hub genes (COL1A2, COL3A1, TAGLN and SPARC) correlated strongly with Cance Associated Fibroblasts and inversely with B-cells, reflecting a collagen-rich stroma. We also observed overlapping expression profiles between GAC and PTT, indicating tumor heterogeneity and a molecular continuum between normal and neoplastic tissues. These integrated insights highlight candidate biomarkers and in GAC.

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