Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
J Cell Physiol. 2021 Oct;236(10):6907-6919. doi: 10.1002/jcp.30350. Epub 2021 Mar 3.
Ovarian cancer (OC) remains the leading cause of cancer-related death among gynecological cancers. The present study examined the role of collagen type V alpha 1 (COL5A1) and the characteristics of COL5A1 as an oncogenic protein in OC. The association of COL5A1 with paclitaxel (PTX)-resistance and stemness in OC was also studied and the multidatabase and big data analyses of the prognostic value, coexpression network, genetic alterations, and tumor-infiltrating immune cells of COL5A1 were elucidated. We found that COL5A1 expression was high in OC cells and tissues. Knockdown of COL5A1 inhibited the proliferation and migration of OC cells. Further study also showed that COL5A1 was overexpressed in PTX-resistant OC cells compared to respective PTX-sensitive cells. Additionally, COL5A1 was more enriched in OC stem cell-like cells. Silencing COL5A1 expression decreased the OC cell resistance to PTX and inhibited the ability of OC-spheroid formation. Survival analysis predicted that the elevated COL5A1 expression was associated with a worse survival outcome and correlated to the tumor stage of OC patients. The estimating relative subsets of RNA transcripts (CIBERSORT) algorithm analysis also unveiled the correlation of several tumor-infiltrating immune cells with the expression of COL5A1. Taken together, our data demonstrate that COL5A1 is a biomarker to predict OC progression and PTX-resistance and represents a promising target for OC treatment.
卵巢癌（OC）仍然是妇科癌症相关死亡的主要原因。本研究探讨了胶原类型 V alpha 1（COL5A1）的作用及其作为 OC 致癌蛋白的特征。还研究了 COL5A1 与紫杉醇（PTX）耐药性和 OC 干性之间的关联，并对 COL5A1 的预后价值、共表达网络、遗传改变和肿瘤浸润免疫细胞进行了多数据库和大数据分析。我们发现 COL5A1 在 OC 细胞和组织中表达较高。COL5A1 的敲低抑制了 OC 细胞的增殖和迁移。进一步的研究还表明，与相应的 PTX 敏感细胞相比，PTX 耐药性 OC 细胞中 COL5A1 表达上调。此外，COL5A1 在 OC 类干细胞样细胞中更为丰富。沉默 COL5A1 表达降低了 OC 细胞对 PTX 的耐药性，并抑制了 OC 球体形成的能力。生存分析预测，COL5A1 表达升高与预后不良相关，并与 OC 患者的肿瘤分期相关。估计相对 RNA 转录子亚群（CIBERSORT）算法分析也揭示了几种肿瘤浸润免疫细胞与 COL5A1 表达的相关性。总之，我们的数据表明 COL5A1 是预测 OC 进展和 PTX 耐药性的生物标志物，代表了 OC 治疗的有希望的靶点。
