Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Oncol Rep. 2019 Jul;42(1):151-175. doi: 10.3892/or.2019.7147. Epub 2019 May 3.
Breast cancer (BC) has a complex etiology and pathogenesis, and is the most common malignant tumor type in females, in USA in 2018, yet its relevant molecular mechanisms remain largely unknown. The collagen type V α‑1 chain (COL5A1) gene is differentially expressed in renal and ovarian cancer. Using bioinformatics methods, COL5A1 was determined to also be a significant gene in BC, but its association with BC has not been sufficiently reported. COL5A1 microarray and relevant clinical data were collected from the Gene Expression Omnibus, The Cancer Genome Atlas and other databases to summarize COL5A1 expression in BC and its subtypes at the mRNA and protein levels. All associated information was comprehensively analyzed by various software. The clinical significance of the mutation was obtained via the cBioPortal. Furthermore, Gene Ontology functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were also performed to investigate the mechanism of COL5A1 in BC. Immunohistochemistry was also conducted to detect and confirm COL5A1 expression. It was determined that COL5A1 was highly expressed in BC tissues, compared with normal tissues at the mRNA level [standard mean difference, 0.84; 95% confidence interval (CI), 0.60‑1.07; P=0.108]. The area under the summary receiver operator characteristic curve for COL5A1 was 0.87 (95% CI, 0.84‑0.90). COL5A1 expression was altered in 32/817 (4%) sequenced samples. KEGG analysis confirmed the most notable pathways, including focal adhesion, extracellular matrix‑receptor interaction and regulation of the actin cytoskeleton. Immunohistochemical detection was used to verify the expression of COL5A1 in 136 selected cases of invasive BC tissues and 55 cases of adjacent normal tissues, while the rate of high expression of COL5A1 in BC was up to 90.4%. These results indicated that COL5A1 is highly expressed at the mRNA and protein levels in BC, and the prognosis of patients with BC with high COL5A1 expression may be reduced; therefore, COL5A1 may be used independently or combined with other detection factors in BC diagnosis.
乳腺癌（BC）的病因和发病机制复杂，是美国女性最常见的恶性肿瘤类型，但其相关分子机制在很大程度上仍不清楚。胶原类型 Vα-1 链（COL5A1）基因在肾和卵巢癌中差异表达。使用生物信息学方法，COL5A1 被确定为 BC 中的一个重要基因，但 COL5A1 与 BC 的相关性尚未得到充分报道。从基因表达综合数据库、癌症基因组图谱和其他数据库中收集 COL5A1 微阵列和相关临床数据，以总结 COL5A1 在 BC 及其亚型中的 mRNA 和蛋白水平表达。通过各种软件综合分析所有相关信息。通过 cBioPortal 获得突变的临床意义。此外，还进行了基因本体论功能注释和京都基因与基因组百科全书（KEGG）通路富集，以研究 COL5A1 在 BC 中的作用机制。还进行了免疫组织化学检测以检测和确认 COL5A1 的表达。结果表明，COL5A1 在 BC 组织中的表达明显高于正常组织[标准均数差，0.84；95%置信区间（CI），0.60-1.07；P=0.108]。COL5A1 的汇总接收者操作特征曲线下面积为 0.87（95%CI，0.84-0.90）。在 817 个测序样本中，有 32 个样本中 COL5A1 的表达发生改变。KEGG 分析证实了最显著的途径，包括粘着斑、细胞外基质-受体相互作用和肌动蛋白细胞骨架的调节。免疫组织化学检测用于验证 136 例浸润性 BC 组织和 55 例相邻正常组织中 COL5A1 的表达，BC 中 COL5A1 高表达率高达 90.4%。这些结果表明，COL5A1 在 BC 中在 mRNA 和蛋白水平上均高表达，COL5A1 高表达的 BC 患者的预后可能降低；因此，COL5A1 可单独或与 BC 诊断中的其他检测因子联合使用。
