Wu Guangzhen, Li Jianyi, Xu Yingkun, Che Xiangyu, Chen Feng, Wang Qifei
Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
J Oncol. 2021 Sep 23;2021:2606213. doi: 10.1155/2021/2606213. eCollection 2021.
The main purpose of this study was to explore the genetic variation, gene expression, and clinical significance of ADAMTSs (a disintegrin and metalloprotease domains with thrombospondin motifs) across cancer types. Analysis of data from the TCGA (The Cancer Genome Atlas) database showed that the ADAMTSs have extensive CNV (copy number variation) and SNV (single nucleotide variation) across cancer types. Compared with normal tissues, the methylation of ADAMTSs in cancer tissues is also significantly different, which affects the expression of ADAMTS gene and the prognosis of cancer patients. Through gene expression analysis, we found that ADAMTS family has significant changes in gene expression across cancer types and is closely related to the prognosis of carcinoma, especially in ccRCC (clear cell renal cell carcinoma). LASSO regression analysis was used to establish a prognostic model based on the ADAMTSs to judge the prognosis of patients with ccRCC. Multiple Cox regression analysis suggested that age, grade, stage, and risk score of the prognostic model of ccRCC were independent prognostic factors in patients with renal clear cell carcinoma. These findings indicate that the ADAMTSs-based survival model can accurately predict the prognosis of patients with ccRCC and suggest that ADAMTSs are a potential prognostic biomarker and therapeutic target in ccRCC.
本研究的主要目的是探讨含血小板反应蛋白基序的解聚素和金属蛋白酶（ADAMTSs）在不同癌症类型中的基因变异、基因表达及临床意义。对来自癌症基因组图谱（TCGA）数据库的数据进行分析表明，ADAMTSs在不同癌症类型中存在广泛的拷贝数变异（CNV）和单核苷酸变异（SNV）。与正常组织相比，癌症组织中ADAMTSs的甲基化也存在显著差异，这影响了ADAMTS基因的表达及癌症患者的预后。通过基因表达分析，我们发现ADAMTS家族在不同癌症类型中的基因表达有显著变化，且与癌症预后密切相关，尤其是在肾透明细胞癌（ccRCC）中。采用套索回归分析基于ADAMTSs建立了一个预后模型，以判断ccRCC患者的预后。多因素Cox回归分析表明，ccRCC预后模型的年龄、分级、分期及风险评分是肾透明细胞癌患者的独立预后因素。这些发现表明，基于ADAMTSs的生存模型能够准确预测ccRCC患者的预后，并提示ADAMTSs是ccRCC中一个潜在的预后生物标志物和治疗靶点。
