Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou 215123, PR China.
Cell Calcium. 2023 Dec;116:102803. doi: 10.1016/j.ceca.2023.102803. Epub 2023 Sep 22.
Calcium-sensing receptor (CASR), primarily found in the parathyroid gland and other tissues, plays a crucial role in sensing and regulating extracellular calcium, which was also aberrantly expressed in human tumors. Nevertheless, a comprehensive analysis of CASR in pan-cancer has yet to be conducted. To gain a better understanding of CASR in pan-cancer, data profiles on CASR cancers were collected from TCGA database. The expression level, clinical significance, prognostic value, and potential mechanisms of CASR in pan-cancer were analyzed via multiple public databases. The functional assays were conducted using human kidney renal clear cell carcinoma (KIRC) cell lines, clinical samples, and nude mice. Our research revealed that the abnormal expression of CASR was found in a variety of tumors. The expression and mutation of CASR were significantly associated with tumor prognosis and stage. Pathway analyses suggested that CASR was involved in the epithelial-mesenchymal transition (EMT) progress. Besides, CASR expression was correlated with immune inhibitory genes and immunotherapy in cancers. Particularly in KIRC, we established that CASR mRNA and protein levels were downregulated in clinical samples and cell lines. Moreover, a Cox regression analysis revealed that CASR was an independent prognostic factor in both TCGA-KIRC samples and clinical samples from our center. In vitro and in vivo experiments revealed that blocking CASR with lentivirus could suppress tumor growth and invasion, and EMT progress in KIRC cells. In summary, our study provides a comprehensive bioinformatic analysis of CASR in pan-cancer, offering deeper insights into its function and the EMT mechanism in KIRC, warranting further investigation.
钙敏感受体 (CASR) 主要存在于甲状旁腺和其他组织中，在感知和调节细胞外钙方面发挥着关键作用，而钙敏感受体在人类肿瘤中也存在异常表达。然而，对癌症中的钙敏感受体（CASR）进行全面分析尚未开展。为了更好地了解癌症中的钙敏感受体（CASR），我们从 TCGA 数据库中收集了有关 CASR 癌症的数据谱。通过多个公共数据库分析了 CASR 在癌症中的表达水平、临床意义、预后价值和潜在机制。使用人肾透明细胞癌（KIRC）细胞系、临床样本和裸鼠进行了功能测定。我们的研究表明，CASR 的异常表达存在于多种肿瘤中。CASR 的表达和突变与肿瘤预后和分期显著相关。通路分析表明，CASR 参与了上皮-间充质转化（EMT）进程。此外，CASR 的表达与癌症中的免疫抑制基因和免疫治疗相关。特别是在 KIRC 中，我们发现 CASR 的 mRNA 和蛋白水平在临床样本和细胞系中均下调。此外，Cox 回归分析表明，CASR 是 TCGA-KIRC 样本和我们中心的临床样本中独立的预后因素。体外和体内实验表明，用慢病毒阻断 CASR 可以抑制 KIRC 细胞的肿瘤生长、侵袭和 EMT 进程。总之，我们的研究提供了癌症中 CASR 的全面生物信息学分析，深入了解了其在 KIRC 中的功能和 EMT 机制，值得进一步研究。
