FAM84B drives colon adenocarcinoma progression via stemness maintenance and tumor microenvironment remodeling
Year: 2026
Type: article
Abstract: Background: FAM84B is oncogenic in multiple malignancies, but its precise role in colon adenocarcinoma (COAD) remains unclear. This study aims to integrate multi-omics analyses with experimental validation to elucidate the functional significance of FAM84B in COAD.Methods: FAM84B expression was analyzed using The Cancer Genome Atlas (TCGA) and single-cell RNA sequencing datasets. Cancer stemness, tumor microenvironment (TME) remodeling, and predicted drug sensitivity were evaluated bioinformatically. Key findings were validated via in vitro assays, in vivo xenografts using FAM84B-overexpressing SW480 cells, and clinical tissue microarrays (TMAs).Results: FAM84B was significantly upregulated in COAD and robustly promoted tumor growth. Pseudotime and single-cell analyses revealed that FAM84B maintained cancer stem cell (CSC) properties, upregulating key markers [PROM1 (CD133), CD44, SOX2, POU5F1 (OCT4), and LGR5]. FAM84B orchestrated a TME phenotypic switch from an immune-engaged to a stroma-dominated state, enhanced pro-tumorigenic intercellular communication, and drove invasion via epithelial-mesenchymal transition (EMT). Furthermore, FAM84B exhibited bidirectional predicted drug sensitivity: FAM84B-high tumors displayed predicted resistance to 5-fluorouracil and oxaliplatin but predicted sensitivity to irinotecan, with the converse pattern in FAM84B-low tumors. Mechanistic networks linked FAM84B to DNA repair, angiogenesis, and drug metabolism. Western blot analysis confirmed that FAM84B overexpression upregulated c-Myc protein and p-c-Myc (Ser62) despite decreased MYC mRNA.Conclusions: FAM84B drives COAD progression by promoting proliferation and invasion, maintaining CSC properties, remodeling the immunosuppressive TME, and bidirectionally modulating predicted drug sensitivity. These findings establish FAM84B as a candidate prognostic biomarker and a promising therapeutic target for personalized COAD treatment.
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224126660