Lu Liqun, Lei Yan, Li Yanling, Wang Lujuan
Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
Aging (Albany NY). 2024 Jan 15;16(2):1484-1495. doi: 10.18632/aging.205440.
Renal cell carcinoma is the most common and most lethal genitourinary tumor. The causes of renal clear cell carcinoma are complex and the heterogeneity of the tumor tissue is high, so patient outcomes are not very satisfactory. Exploring biomarkers in the progression of renal clear cell carcinoma is crucial to improve the diagnosis and guide the treatment of renal clear cell carcinoma. LRP6 is a co-receptor of the Wnt/β-catenin signaling pathway, which is involved in cell growth, inflammation and cell transformation through activation of the Wnt/β-catenin signaling pathway. Abnormal expression of LRP6 is associated with the malignant phenotype, metastatic potential and poor prognosis of various tumors. In this study, we found that LRP6 was abnormally highly expressed in a variety of tumors and significantly correlated with microsatellite instability, tumor mutation burden, and immune cell infiltration and immune checkpoint expression in a variety of tumors. Moreover, we found that LRP6 was significantly associated with the prognosis of renal clear cell carcinoma. Further we found a significant correlation between LRP6 and the expression of m6A-related genes and ferroptosis-related genes. Finally, we also found a significant correlation between the expression of LRP6 and the sensitivity to common drugs used in kidney clear cell carcinoma treatment. These results suggest that LRP6 is likely to be a potential target for kidney clear cell carcinoma treatment.
肾细胞癌是最常见且致死率最高的泌尿生殖系统肿瘤。肾透明细胞癌的病因复杂,肿瘤组织的异质性高,因此患者的治疗效果不太理想。探索肾透明细胞癌进展过程中的生物标志物对于改善其诊断和指导治疗至关重要。低密度脂蛋白受体相关蛋白6(LRP6)是Wnt/β-连环蛋白信号通路的共受体,通过激活Wnt/β-连环蛋白信号通路参与细胞生长、炎症和细胞转化。LRP6的异常表达与多种肿瘤的恶性表型、转移潜能及不良预后相关。在本研究中,我们发现LRP6在多种肿瘤中异常高表达,且与多种肿瘤的微卫星不稳定性、肿瘤突变负荷、免疫细胞浸润及免疫检查点表达显著相关。此外,我们发现LRP6与肾透明细胞癌的预后显著相关。进一步地,我们发现LRP6与m6A相关基因及铁死亡相关基因的表达存在显著相关性。最后,我们还发现LRP6的表达与肾透明细胞癌治疗中常用药物的敏感性存在显著相关性。这些结果表明,LRP6很可能是肾透明细胞癌治疗的一个潜在靶点。