高表达的COL10A1促进乳腺癌进展并预示不良预后。
High expression COL10A1 promotes breast cancer progression and predicts poor prognosis.
作者信息
Zhou Weijian, Li Yuting, Gu Dingyi, Xu Junying, Wang Runjie, Wang Huiyu, Liu Chaoying
机构信息
Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China.
出版信息
Heliyon. 2022 Oct 17;8(10):e11083. doi: 10.1016/j.heliyon.2022.e11083. eCollection 2022 Oct.
BACKGROUND
As a common malignant disease in females, breast cancer (BCa) causes increasing numbers of cancer-related death. Collagen X alpha 1 chain (COL10A1) plays a critical role in the oncogenesis and progression of malignant tumors. However, a systematic analysis of COL10A1 in BCa has not been conducted.
METHODS
The COL10A1 expression level and prognostic value in BCa were defined through the Cancer Genome Atlas (TCGA) as well as the Kaplan-Meier plotter data respectively. The expression pattern of COL10A1 was subsequently confirmed on tissue microarray (TMA) by immunochemistry (IHC) staining. Moreover, cellular functional assays which aimed to evaluate cell proliferation, migration, invasion, and apoptosis, were conducted to investigate the oncogenic activity of COL10A1 in BCa. Then, Tumor Immune Estimation Resource (TIMER) was adopted to determine the association between COL10A1 expression and immune cell infiltration.
RESULTS
Bioinformatics analysis revealed that COL10A1 was significantly overexpressed and had notable prognostic value, especially for distant metastasis-free survival (DMFS) in BCa. Moreover, IHC analysis of 140 BCa tissues on TMA chips exhibited the overexpression of COL10A1 was correlated to advanced clinical stage, poor overall survival (OS), and worse recurrence-free survival (RFS). Besides, knockdown of COL10A1 remarkably suppressed cell proliferation, migration, and invasion in BCa cells, and notably promoted cell apoptosis as well. Furthermore, COL10A1 was positively associated with immune cell infiltration including B cell, CD8 T cell, CD4 T cell, macrophage, neutrophil, and dendritic cell.
CONCLUSION
The results revealed that COL10A1 is a novel oncogene and could serve as a potential prognostic biomarker in BCa. Besides, the downregulation of COL10A1 could inhibit BCa progression, which could be a potential target for BCa therapy.
背景
乳腺癌（BCa）作为女性常见的恶性疾病，导致癌症相关死亡人数不断增加。胶原蛋白Xα1链（COL10A1）在恶性肿瘤的发生和发展中起关键作用。然而，尚未对BCa中的COL10A1进行系统分析。
方法
分别通过癌症基因组图谱（TCGA）以及Kaplan-Meier绘图仪数据确定COL10A1在BCa中的表达水平和预后价值。随后通过免疫组织化学（IHC）染色在组织芯片（TMA）上证实COL10A1的表达模式。此外，进行旨在评估细胞增殖、迁移、侵袭和凋亡的细胞功能试验，以研究COL10A1在BCa中的致癌活性。然后，采用肿瘤免疫估计资源（TIMER）来确定COL10A1表达与免疫细胞浸润之间的关联。
结果
生物信息学分析显示，COL10A1显著过表达且具有显著的预后价值，尤其是对BCa的无远处转移生存期（DMFS）。此外，对TMA芯片上140例BCa组织的IHC分析表明，COL10A1的过表达与晚期临床分期、较差的总生存期（OS）和无复发生存期（RFS）相关。此外，敲低COL10A1可显著抑制BCa细胞的增殖、迁移和侵袭，并显著促进细胞凋亡。此外，COL10A1与包括B细胞、CD8 T细胞、CD4 T细胞、巨噬细胞、中性粒细胞和树突状细胞在内的免疫细胞浸润呈正相关。
结论
结果表明，COL10A1是一种新型癌基因，可作为BCa潜在的预后生物标志物。此外，COL10A1的下调可抑制BCa进展，这可能是BCa治疗的潜在靶点。
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