Wu Xin-Qiang, Shang Zhi, Xiong Cui, Xu Wen-Hao, Dai Bo, Chen Yu-Ling, Feng Yu-Yang, Wang Yue, Su Jia-Qi, Zhao Jian-Yuan, Zhang Hai-Liang, Shi Yan, Qu Yuan-Yuan, Ye Ding-Wei
Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, 313000 China.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.
Phenomics. 2024 Aug 5;4(4):365-378. doi: 10.1007/s43657-024-00169-7. eCollection 2024 Aug.
Increasing evidence indicates that Calumenin (CALU), which is localized in the endoplasmic reticulum, is significantly associated with tumor progression. However, the effect of CALU on patients with clear cell renal cell carcinoma (ccRCC) is unknown. By integrating multi-omics data and molecular biology experiments, we found that CALU expression was significantly increased in tumors compared with normal tissues, and the pathological grade and prognosis of patients were correlated with CALU expression. Next, knockdown or ectopic expression of CALU could affect the proliferative and invasive abilities of ccRCC cells. Moreover, immune landscape characterization revealed that CALU expression was positively associated with neutrophils and macrophages, whereas it was negatively associated with natural killer T cells and CD8 T cells. Single-cell sequencing showed that the localization and binding targets of CALU mainly involved monocytes/macrophages and CD4 and CD8 T-cells. Sensitivity analysis of common chemotherapeutic drugs showed that high expression of CALU could sensitize chemotherapeutic drugs such as 5Z-7-Oxozeaenol, AMG-706 and Cytarabine, but could lead to drug resistance to chemotherapeutic drugs such as Embelin, Salubrinal and Tipifarnib. We demonstrated a significant correlation between high CALU expression and poor patient survival. Further, we demonstrated a correlation between CALU expression, tumor microenvironment, and the sensitivity of patients to common chemo- and immuno-therapy drugs. Thus, our results indicate that CALU could be a biomarker and designing personalized treatment approaches for ccRCC patients.
The online version contains supplementary material available at 10.1007/s43657-024-00169-7.
越来越多的证据表明，定位于内质网的钙网蛋白（CALU）与肿瘤进展显著相关。然而，CALU对透明细胞肾细胞癌（ccRCC）患者的影响尚不清楚。通过整合多组学数据和分子生物学实验，我们发现与正常组织相比，肿瘤中CALU表达显著增加，且患者的病理分级和预后与CALU表达相关。接下来，CALU的敲低或异位表达可影响ccRCC细胞的增殖和侵袭能力。此外，免疫景观特征显示，CALU表达与中性粒细胞和巨噬细胞呈正相关，而与自然杀伤T细胞和CD8 T细胞呈负相关。单细胞测序表明，CALU的定位和结合靶点主要涉及单核细胞/巨噬细胞以及CD4和CD8 T细胞。常见化疗药物的敏感性分析表明，CALU高表达可使5Z-7-氧代玉米烯醇、AMG-706和阿糖胞苷等化疗药物敏感，但会导致对恩贝林、沙芦比诺和替匹法尼等化疗药物产生耐药性。我们证明了CALU高表达与患者不良生存之间存在显著相关性。此外，我们证明了CALU表达、肿瘤微环境与患者对常见化疗和免疫治疗药物的敏感性之间存在相关性。因此，我们的结果表明，CALU可能是一种生物标志物，可为ccRCC患者设计个性化治疗方案。
在线版本包含可在10.1007/s43657-024-00169-7获取的补充材料。
