Genomics Research Center, Academia Sinica, Taipei, Taiwan.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
J Cell Mol Med. 2023 Mar;27(5):672-686. doi: 10.1111/jcmm.17690. Epub 2023 Feb 18.
Follistatin-like (FSTL) family members are associated with cancer progression. However, differences between FSTL members with identical cancer types have not been systematically investigated. Among the most malignant tumours worldwide, colorectal cancer (CRC) has high metastatic potential and chemoresistance, which makes it challenging to treat. A systematic examination of the relationship between the expression of FSTL family members in CRC will provide valuable information for prognosis and therapeutic development. Based on large cohort survival analyses, we determined that FSTL3 was associated with a significantly worse prognosis in CRC at the RNA and protein levels. Immunohistochemistry staining of CRC specimens revealed that FSTL3 expression levels in the cytosol were significantly associated with a poor prognosis in terms of overall and disease-free survival. Molecular simulation analysis showed that FSTL3 participated in multiple cell motility signalling pathways via the TGF-β1/TWIST1 axis to control CRC metastasis. The findings provide evidence of the significance of FSTL3 in the oncogenesis and metastasis of CRC. FSTL3 may be useful as a diagnostic or prognostic biomarker, and as a potential therapeutic target.
卵泡抑素样 (FSTL) 家族成员与癌症进展有关。然而,具有相同癌症类型的 FSTL 成员之间的差异尚未系统研究。在全球最恶性的肿瘤中,结直肠癌 (CRC) 具有高转移潜能和化疗耐药性,这使得治疗极具挑战性。系统检查 FSTL 家族成员在 CRC 中的表达关系将为预后和治疗开发提供有价值的信息。基于大型队列生存分析,我们确定 FSTL3 在 RNA 和蛋白质水平上与 CRC 的预后显著相关。CRC 标本的免疫组织化学染色显示,FSTL3 在细胞质中的表达水平与总生存和无病生存的预后显著相关。分子模拟分析表明,FSTL3 通过 TGF-β1/TWIST1 轴参与多个细胞运动信号通路,从而控制 CRC 的转移。这些发现为 FSTL3 在 CRC 的发生和转移中的重要性提供了证据。FSTL3 可用作诊断或预后标志物,以及潜在的治疗靶点。