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Cartilage oligomeric matrix protein acts as a molecular biomarker in multiple cancer types

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Abstract

Purpose

The main function of cartilage oligomeric matrix protein (COMP) is to maintain the synthesis and stability of the extracellular matrix by interacting with collagen. At present, there are relatively few studies on the role of this protein in tumors. This study aimed to explore the relationship between COMP and pan-cancer, and analyzed its diagnostic and prognostic value.

Methods

The Cancer Genome Atlas database, the Genotype-Tissue Expression database and the Cancer Cell Line Encyclopedia database was used for gene expression analysis. The receiver operating characteristic curve was used to assess the diagnostic value of COMP in pan-cancer. Kaplan–Meier plots were used to assess the relationship between COMP expression and prognosis of cancers. R software v4.1.1 was used for statistical analysis, and the ggplot2 package was used for visualization.

Results

COMP was significantly overexpressed in 15 human cancers and showed significantly difference in 12 molecular subtypes and 16 immune subtypes. In addition, the expression of COMP is associated with tumor immune evasion. The ROC curve showed that the expression of COMP could predict the occurrence of 16 kinds of tumors with relative accuracy, including adrenocortical carcinoma (ACC) (AUC = 0.737), breast invasive carcinoma (BRCA) (AUC = 0.896), colon adenocarcinoma (COAD) (AUC = 0.760), colon adenocarcinoma/rectum adenocarcinoma esophageal carcinoma (COADREAD) (AUC = 0.775), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC) (AUC = 0.875), kidney renal papillary cell carcinoma (KIRP) (AUC = 0.773), kidney chromophobe (KICH) (AUC = 0.809), ovarian serous cystadenocarcinoma (OV) (AUC = 0.906), prostate adenocarcinoma (PRAD) (AUC = 0.721), pancreatic adenocarcinoma (PAAD) (AUC = 0.944), rectum adenocarcinoma (READ) (AUC = 0.792), skin cutaneous melanoma (SKCM) (AUC = 0.746), stomach adenocarcinoma (STAD) (AUC = 0.711), testicular germ cell tumors (TGCT) (AUC = 0.823), thymoma (THYM) (AUC = 0.777) and uterine carcinosarcoma (UCS) (AUC = 0.769). Furthermore, COMP expression was correlated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ACC (OS, HR = 4.95, DSS, HR = 5.55, PFI, HR = 2.79), BLCA (OS, HR = 1.59, DSS, HR = 1.72, PFI, HR = 1.36), KIRC (OS, HR = 1.36, DSS, HR = 1.94, PFI, HR = 1.57) and COADREAD (OS, HR = 1.46, DSS, HR = 1.98, PFI, HR = 1.43). We selected previously unreported bladder urothelial carcinoma (BLCA) for further study and found that COMP could be an independent risk factor for OS, DSS and PFI. Moreover, we found differentially expressed genes of COMP in BLCA and obtained top 10 hub genes, including LGR4, LGR5, RSPO2, RSPO1, RSPO3, RNF43, ZNRF3, FYN, LYN and SYK. Finally, we verified the function of COMP at the cellular level by using J82 and T24 cells and found that knockdown of COMP could significantly inhibit migration and invasion. This finding supports that COMP could be a potential biomarker for pan-cancer diagnosis and prognosis encompassing tumor microenvironment, disease stage and prognosis.

Conclusion

This finding supports that COMP could be a potential biomarker for pan-cancer diagnosis and prognosis encompassing tumor microenvironment, disease stage and prognosis.

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All data reported are included and represented in the manuscript.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (81803541) and Shanghai Science and Technology Development Foundation (22140901900).

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Author notes

  1. Bingjie Guo and Yajing Wang have equally contributed to the article.

Authors and Affiliations

  1. Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Bingjie Guo

  2. Department of Traditional Chinese Medicine, Second Military Medical University/Naval Medical University, Shanghai, China

    Yajing Wang

  3. Department of Hepatobiliary and Pancreatic Surgery, Changhai Hospital Affiliated to Naval Medical University, 168 Chang Hai Road, Shanghai, 200433, China

    Wenyu Liu

  4. Department of Pharmacology, Second Military Medical University/Naval Medical University, 325 Guo He Road, Shanghai, 200433, China

    Sailong Zhang

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  1. Bingjie Guo
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Contributions

Bingjie Guo and Yajing Wang contributed equally to the article. Bingjie Guo and Yajing Wang performed the statistical analysis and drew the pictures. Sailong Zhang and Wenyu Liu contributed to the design and writing of the study. All authors approved the final version of the manuscript.

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Correspondence to Wenyu Liu or Sailong Zhang.

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Guo, B., Wang, Y., Liu, W. et al. Cartilage oligomeric matrix protein acts as a molecular biomarker in multiple cancer types. Clin Transl Oncol 25, 535–554 (2023). https://doi.org/10.1007/s12094-022-02968-8

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