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利用多组学数据剖析 Calumenin 在透明细胞肾细胞癌恶性肿瘤及微环境异质性中的意义

英文原题:Dissecting the Implications of Calumenin in Malignancy and Heterogeneity of the Microenvironment of Clear Cell Renal Cell Carcinoma Using Multi-Omics Data.

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Dissecting the Implications of Calumenin in Malignancy and Heterogeneity of the Microenvironment of Clear Cell Renal Cell Carcinoma Using Multi-Omics Data.

PubMed 2024/08/05(内容时间) Phenomics Q1 · IF 5.5(JCR 2025)

研究概要

我们的结果表明,CALU可能成为ccRCC患者的生物标志物,并有助于设计个性化治疗方案。

中文摘要

未标注:越来越多的证据表明,定位于内质网的 Calumenin(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,CALU 在肿瘤中的表达显著升高,且患者的病理分级和预后与 CALU 表达相关。接下来,敲低或异位表达 CALU 可影响 ccRCC 细胞的增殖和侵袭能力。此外,免疫景观表征显示,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。单细胞测序显示,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。对常见化疗药物的敏感性分析显示,CALU 高表达可使 5Z-7-Oxozeaenol、AMG-706 和 Cytarabine 等化疗药物增敏,但可导致对 Embelin、Salubrinal 和 Tipifarnib 等化疗药物耐药。我们证明了 CALU 高表达与患者生存不良之间存在显著相关性。进一步,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敏感性之间的相关性。因此,我们的结果表明,CALU 可能成为 ccRCC 患者的生物标志物,并有助于设计个性化治疗方案。补充信息:在线版本包含补充材料,可在 10.1007/s43657-024-00169-7 获取。

展开英文摘要原文

UNLABELLED: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-024-00169-7.

论文信息

作者
Wu XQ、Shang Z、Xiong C、Xu WH、Dai B、Chen YL、Feng YY、Wang Y
第一作者单位
Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, 313000 China.China
通讯作者单位
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.China
期刊
Phenomics (Cham, Switzerland)2024 Aug
原文标识
PubMed 39583311 · DOI 10.1007/s43657-024-00169-7