Paik E Sun, Chang Chi-Son, Chae Ye Lin, Oh So Young, Byeon Sun-Ju, Kim Chul Jung, Lee Yoo-Young, Kim Tae-Joong, Lee Jeong-Won, Kim Byoung-Gie, Choi Chel Hun
Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Front Oncol. 2021 Nov 8;11:770103. doi: 10.3389/fonc.2021.770103. eCollection 2021.
BRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in several cancers, the objective of this study was to investigate BRCA1 expression using immunohistochemistry (IHC) in cervical cancer and its possible prognostic relevance.
Seventy patients with cervical cancer were enrolled in this study. Samples from each tumor were stained for BRCA1 and reviewed independently by gynecologic pathologists blinded to the BRCA status. Kaplan-Meier methods were used to estimate overall survival according to BRCA1 expression. Differentially expressed genes (DEGs) by BRCA1 expression were selected using GSE44001 dataset, which included 300 samples treated with radical hysterectomy. In addition, cox regression analysis with backward elimination was performed to select independent prognostic markers. Gene set enrichment analysis (GSEA) was done using these DEGs.
BRCA1 IHC was positive in 62.9% (44/70) of cases. Patients with BRCA1 expression showed better overall survival (100% . 76.2%, HR 0.20, 95% CI 0.04 - 0.99, p = 0.028) than those without BRCA1 expression. Analysis of gene expression profiles according to expression identified 321 differentially expressed mRNAs. Gene set enrichment analysis results showed two dysregulated pathways (VEGF_A_UP.V1_DN and E2F1_UP.V1_UP). Of these DEGs, alterations of 20 gene signatures were found to be independently associated with survival outcomes of patients.
BRCA1 expression in cervical cancer tissue is associated with survival. In addition, the identification of specific gene alterations associated with BRCA1 expression could help to provide individualized prediction in these patients.
BRCA1表达可通过多种机制丧失，包括种系或体细胞突变以及启动子高甲基化。鉴于BRCA1缺失作为几种癌症的预测和预后生物标志物具有潜在重要性，本研究的目的是使用免疫组织化学（IHC）研究宫颈癌中BRCA1的表达及其可能的预后相关性。
本研究纳入了70例宫颈癌患者。对每个肿瘤样本进行BRCA1染色，并由对BRCA状态不知情的妇科病理学家独立进行评估。采用Kaplan-Meier方法根据BRCA1表达估计总生存期。使用包含300例接受根治性子宫切除术治疗样本的GSE44001数据集选择由BRCA1表达差异表达的基因（DEG）。此外，进行逐步回归的cox回归分析以选择独立的预后标志物。使用这些DEG进行基因集富集分析（GSEA）。
BRCA1免疫组化在62.9%（44/70）的病例中呈阳性。有BRCA1表达的患者总生存期优于无BRCA1表达的患者（100% 对76.2%，HR 0.20，95%CI 0.04 - 0.99，p = 0.028）。根据BRCA1表达分析基因表达谱，鉴定出321个差异表达的mRNA。基因集富集分析结果显示两条失调的通路（VEGF_A_UP.V1_DN和E2F1_UP.V1_UP）。在这些DEG中，发现20个基因特征的改变与患者的生存结果独立相关。
宫颈癌组织中BRCA1表达与生存相关。此外，鉴定与BRCA1表达相关的特定基因改变有助于为这些患者提供个性化预测。
