Yicong Yao, Wang Yi, Denglong Wu, Baoying Hu
School of Medicine, Tongji University, Shanghai, China.
Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Front Oncol. 2021 May 24;11:666418. doi: 10.3389/fonc.2021.666418. eCollection 2021.
CDC6 (Cell division control protein 6), located at chromosome 17q21.3, plays an important role in the early stage of DNA replication and has unique functions in various malignant tumors. Here, we evaluate the relationship between CDC6 expression and oncology outcomes in patients with clear cell renal cell carcinoma (ccRCC).
A retrospective analysis of 118 ccRCC patients in Affiliated Hospital of Nantong University from 2015 to 2017 was performed. Triplicate tissue microarrays (TMA) were prepared from formalin-fixed and paraffin-embedded specimens. Immunohistochemistry (IHC) was conducted to evaluate the relationship between CDC6 expression and standard pathological features and prognosis. The RNA sequencing data and corresponding clinical information were acquired from the TCGA database. GSEA was used to identify signal pathways related to CDC6. Cox regression analysis was used to assess independent prognostic factors. In addition, the relationship between CDC6 and immunity was also investigated.
The results of Kaplan-Meier curve indicated that the OS of the patients with high expression of CDC6 was shorter than that of the patients with low CDC6 expression. Integrating the TCGA database and IHC staining, the results showed that CDC6 in ccRCC tissue was obviously up-regulated compared with adjacent normal kidney tissue. The results of Logistic regression analysis demonstrated that ccRCC patients with high expression of CDC6 are more likely to develop advanced disease than ccRCC patients with low CDC6 expression. The results of GSEA showed that the high expression of CDC6 was related to multiple signaling pathways. As for immunity, it was also related to TMB, immune checkpoint molecules, tumor microenvironment and immune infiltration. There were significantly correlations with CDC6 and immune cell infiltration levels and tumor microenvironment. The results of further results of the TCGA database showed that CDC6 was obviously related to immune checkpoint molecules and immune cells.
Increased expression of CDC6 is a potentially prognostic factor of poor prognosis in ccRCC patients.
细胞分裂控制蛋白6（CDC6）位于17号染色体q21.3区域，在DNA复制早期发挥重要作用，在多种恶性肿瘤中具有独特功能。在此，我们评估透明细胞肾细胞癌（ccRCC）患者中CDC6表达与肿瘤学结局之间的关系。
对南通大学附属医院2015年至2017年的118例ccRCC患者进行回顾性分析。从福尔马林固定、石蜡包埋的标本中制备三重组织芯片（TMA）。进行免疫组织化学（IHC）以评估CDC6表达与标准病理特征及预后之间的关系。从TCGA数据库获取RNA测序数据及相应临床信息。采用基因集富集分析（GSEA）来识别与CDC6相关的信号通路。采用Cox回归分析评估独立预后因素。此外，还研究了CDC6与免疫的关系。
Kaplan-Meier曲线结果表明，CDC6高表达患者的总生存期短于CDC6低表达患者。整合TCGA数据库和IHC染色结果显示，与相邻正常肾组织相比，ccRCC组织中的CDC6明显上调。Logistic回归分析结果表明，与CDC6低表达的ccRCC患者相比，CDC6高表达的ccRCC患者更易发生晚期疾病。GSEA结果显示，CDC6高表达与多种信号通路相关。至于免疫，它还与肿瘤突变负荷（TMB）、免疫检查点分子、肿瘤微环境和免疫浸润有关。CDC6与免疫细胞浸润水平和肿瘤微环境存在显著相关性。TCGA数据库的进一步结果显示，CDC6与免疫检查点分子和免疫细胞明显相关。
CDC6表达增加是ccRCC患者预后不良的潜在预后因素。
