Qian Xiaojun, Jia Wei, Li Yuntian, Chen Jian, Zhang Jinguo, Sun Yubei
University of Science and Technology of China Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine Hefei China.
Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, P.R. China.
Curr Med Chem. 2025 Apr 7. doi: 10.2174/0109298673351943250314074632.
Collagen type IV alpha 1 chain (COL4A1), which has been proven to be a potential biomarker in Gastric Cancer (GC), but its role in tumors and the tumor microenvironment (TME) needs further explanation.
We analysed the relationship between COL4A1 and clinical characteristics based on The Cancer Genome Atlas (TCGA) database and verified by tissue microarrays as well as GC cell lines using immunohistochemistry, Q-PCR, western blot, cell proliferation assays, colony formation assays, cell invasion and migration assays. The immune infiltration and drug sensitivity information between high and low COL4A1 expression were analysed by R package and pRRophetic package. Finally, we established a nomogram based on COL4A1 expression using the bootstrap method.
COL4A1 was overexpressed in gastric carcinoma compared with normal gastric tissue, indicating a poor prognosis of GC patients in the TCGA database which were also validated by GC tissue microarrays. GO, KEGG and hallmark enrichment analyses indicated that COL4A1 was mainly associated with the extracellular matrix than malignant proliferation. By siRNA transfection, we found that COL4A1 knockdown inhibited cell colony formation, invasion and migration but did not affect cell proliferation, similar to previous results. Immune infiltration and drug sensitivity analysis showed that COL4A1 was negatively correlated with antitumor immunity and positively correlated with multidrug resistance. By developing a nomogram model based on 8 risk factors, including COL4A1, patients with better clinical outcomes could be accurately distinguished.
This study established COL4A1 as a prognostic marker and a potential therapeutic target in gastric cancer. Our findings demonstrate that COL4A1 enhances tumor progression and multidrug resistance while inhibiting antitumor immunity. These results underscore the significance of COL4A1 in gastric cancer and suggest its potential for developing targeted therapies.
IV型胶原蛋白α1链（COL4A1）已被证明是胃癌（GC）的潜在生物标志物，但其在肿瘤及肿瘤微环境（TME）中的作用仍需进一步阐释。
我们基于癌症基因组图谱（TCGA）数据库分析了COL4A1与临床特征之间的关系，并通过组织芯片以及使用免疫组化、Q-PCR、蛋白质免疫印迹、细胞增殖试验、集落形成试验、细胞侵袭和迁移试验的GC细胞系进行验证。通过R包和pRRophetic包分析了COL4A1高表达和低表达之间的免疫浸润和药物敏感性信息。最后，我们使用自助法基于COL4A1表达建立了列线图。
与正常胃组织相比，COL4A1在胃癌中过表达，这表明TCGA数据库中GC患者的预后较差，这也通过GC组织芯片得到了验证。基因本体论（GO）、京都基因与基因组百科全书（KEGG）和特征富集分析表明，COL4A1主要与细胞外基质相关，而非恶性增殖。通过小干扰RNA（siRNA）转染，我们发现COL4A1基因敲低抑制了细胞集落形成、侵袭和迁移，但不影响细胞增殖，这与之前的结果相似。免疫浸润和药物敏感性分析表明，COL4A1与抗肿瘤免疫呈负相关，与多药耐药呈正相关。通过开发基于包括COL4A1在内的8个风险因素的列线图模型，可以准确区分临床结局较好的患者。
本研究将COL4A1确立为胃癌的预后标志物和潜在治疗靶点。我们的研究结果表明，COL4A1增强肿瘤进展和多药耐药，同时抑制抗肿瘤免疫。这些结果强调了COL4A1在胃癌中的重要性，并表明其在开发靶向治疗方面的潜力。
