Bioinformatics analysis of COMMD family in pan-cancer reveals potential biomarkers and therapeutic targets

Abstract

The copper-metabolism Murr1 domain (COMMD) protein family plays an essential role in tumours and the immune system. However, the multi-omics characterisation of COMMD family genes and their role in tumour patients has yet to be explored. We collected data from 33 types of cancer and conducted a comprehensive analysis of the expression abnormalities, diagnostic and prognostic roles, subcellular localisation, pathway enrichment, immune microenvironment and immune checkpoint associations of COMMD family genes in these diseases. We also predicted patient responses to immunotherapy using ICIs. Finally, we confirmed the role of COMMD7 in ccRCC and bladder cancer through in vivo and in vitro experiments. We found differential expression and diagnostic biomarker value of the COMMD family of proteins in pan-cancer, and also found that they play a key role in the tumour microenvironment. COMMD proteins are closely related to common immune checkpoints, TMBs and MSIs, and COMMD family proteins can predict immunotherapy response in patients with various cancers. Finally, knockdown of COMMD7 was found to inhibit the progression of ccRCC and bladder cancer cells, as verified by in vivo and in vitro experiments. Our study highlights the great potential of COMMDs as prognostic and immunotherapeutic response biomarkers, which could pave the way for further research into tumour infiltration mechanisms and the therapeutic potential of COMMDs in cancer.

Keywords: Bladder cancer; COMMD family; COMMD7; Pan-cancer; Tumour microenvironment; ccRCC.

Fig. 1

COMMDs family genes are dysregulated in cancer expression.

Fig. 2

Diagnostic and prognostic analysis of COMMD family genes. (A) Diagnostic ROC curves of COMMD family genes in pan-cancer. an AUC > 0.9 is considered a high diagnostic value, 0.9 ≥ AUC > 0.7 is an intermediate diagnostic value, and 0.7 ≥ AUC > 0.5 is a low diagnostic value. (B) Results of DFI, DSS, OS and PFI prognostic analysis of COMMD family genes in pan-cancer.

Fig. 3

Protein localisation and functional enrichment analysis of COMMD family members. (A) Immunofluorescence images of COMMD family member proteins. (B) Network map of COMMD family members and other related role proteins. (C-D) Heatmap of enrichment of each COMMD family member in Hallmark signalling pathway.

Fig. 4

Association of COMMD family members with the immune microenvironment. (A) Heatmap of the association of COMMD family members with immune infiltrating cells. Correlation of COMMD family genes with CTLA4 (B), PD-1 (C) and PD-L1 (D) in pan-cancer.

Fig. 5

Association between COMMD family and immunotherapy. Correlation of COMMD family genes with TMB (A) and MSI (B) in pan-cancer. (C) Predictive analysis of COMMDs expression related immunotherapy by TISMO database.

Fig. 6

COMMD7 promotes growth and metastasis of ccrcc and bladder cancer cells in vivo and in vitro. Plate cloning assay (A-B), transwell cell migration ability (C-D), and wound healing ability assay (E–F) of renal clear cell carcinoma (786-O and ACHN) and bladder cancer cells (T24 and UM-UC3) transfected with COMMD7 lentivirus. (G-I) Knockdown of COMMD7 significantly inhibited tumour growth, such as tumour growth rate, tumour weight. Note * p < 0.05, **p < 0.01, ***p < 0.001.