Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China.
Ann Surg Oncol. 2024 May;31(5):3502-3512. doi: 10.1245/s10434-023-14370-x. Epub 2024 Mar 1.
Esophageal squamous carcinoma (ESCC) is a gastrointestinal malignancy with a high mortality, but the tumorigenesis is still unclear, restricting the target therapy development of ESCC. We explored the role of COL8A1 in ESCC development.
Tissue microarrays were used to investigate the expression level of COL8A1 in ESCC tissues. The association between COL8A1 and the overall survival of ESCC patients was assessed. The effect of differential COL8A1 expression on tumor growth was investigated by the xenograft model. The regulation of COL8A1 on tumor growth, migration, and invasion was studied by using ESCC cell lines. The signal transduction pathways involved in COL8A1 were bioinformatically profiled and validated.
The COL8A1 was significantly expressed in cancerous tissues and was associated with poor prognosis in patients with ESCC. In vivo, the tumor growth obviously declined after inhibition of the COL8A1 expression. The abilities of cell proliferation and invasion were both decreased when the expression of COL8A1 was knockdown in ESCC cell line. Furthermore, we found the inactivation of the PI3K/AKT pathway that was mediated by knockdown of COL8A1 in ESCC cells, which was reversed with COL8A1 overexpression, whereas the cell proliferation and invasion ability were restored.
This is the first report that COL8A1 promote ESCC progression, which hopefully will provide a theoretical basis for clinical targeting of ESCC.
食管鳞状细胞癌（ESCC）是一种死亡率较高的胃肠道恶性肿瘤，但肿瘤发生机制仍不清楚，限制了 ESCC 的靶向治疗发展。我们探索了 COL8A1 在 ESCC 发展中的作用。
使用组织微阵列检测 ESCC 组织中 COL8A1 的表达水平。评估 COL8A1 与 ESCC 患者总生存率之间的关联。通过异种移植模型研究差异表达 COL8A1 对肿瘤生长的影响。利用 ESCC 细胞系研究 COL8A1 对肿瘤生长、迁移和侵袭的调节作用。通过生物信息学方法分析和验证 COL8A1 参与的信号转导途径。
COL8A1 在癌组织中明显表达，并与 ESCC 患者的预后不良相关。在体内，抑制 COL8A1 表达后肿瘤生长明显下降。当 ESCC 细胞系中 COL8A1 的表达被敲低时，细胞增殖和侵袭能力均降低。此外，我们发现 COL8A1 敲低介导的 PI3K/AKT 通路失活在 ESCC 细胞中，而 COL8A1 过表达则逆转了这一现象，同时恢复了细胞增殖和侵袭能力。
这是首次报道 COL8A1 促进 ESCC 进展，有望为 ESCC 的临床靶向治疗提供理论依据。
