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

Xin-Qiang Wu; Zhi Shang; Cui Xiong; Wen-Hao Xu; Bo Dai; Yu-Ling Chen; Yu-Yang Feng; Yue Wang; Jia-Qi Su; Jian-Yuan Zhao; Hai-Liang Zhang; Yan Shi; Yuan-Yuan Qu; Ding-Wei Ye

doi:10.1007/s43657-024-00169-7

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

Phenomics. 2024 Aug 5;4(4):365-378. doi: 10.1007/s43657-024-00169-7. eCollection 2024 Aug.

Authors

Xin-Qiang Wu^#^{1

2

3}, Zhi Shang^#^{2

3}, Cui Xiong^#¹, Wen-Hao Xu^{2

3}, Bo Dai^{2

3}, Yu-Ling Chen⁴, Yu-Yang Feng⁵, Yue Wang^{2

3}, Jia-Qi Su^{2

3}, Jian-Yuan Zhao⁴, Hai-Liang Zhang^{2

3}, Yan Shi⁴, Yuan-Yuan Qu^{2

3}, Ding-Wei Ye^{2

3}

Affiliations

¹ Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, 313000 China.
² Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.
³ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
⁴ Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092 China.
⁵ The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011 China.

^# Contributed equally.

PMID: 39583311
PMCID: PMC11584829 (available on 2025-08-01)
DOI: 10.1007/s43657-024-00169-7

Abstract

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.

Keywords: Biomarker; Calumenin; Clear cell renal cell carcinoma; Prognosis; Tumor microenvironment.

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