A comprehensive investigation on pan-cancer impacts of constitutive centromere associated network gene family by integrating multi-omics data: A CONSORT-compliant article

Our plain-English summary of A comprehensive investigation on pan-cancer impacts of constitutive centromere associated network gene family by integrating multi-omics data: A CONSORT-compliant article, by H. Su, Y. Fan, Z. Wang, et al (Medicine, 2022).

The study

• Authors: H. Su, Y. Fan, Z. Wang, L. Jiang
• Journal: Medicine
• Published: 2022;101(7):e28821
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The constitutive centromere associated network (CCAN) complex played a critical role in connecting the centromere with the mitotic spindle during mitosis and meiosis. Many studies have indicated that CCAN is related to the tumorigenesis and cancer development. Nonetheless, the overview of CCAN gene family in pan-cancer remain incompletely understood.

Methods: We performed a comprehensive investigation on pan-cancer impacts of CCAN by integrating multi-omics data. We comprehensively investigated the expression profile, kyoto encyclopedia of genes and genomes (kegg) pathway, mutation, copy number variation, tumor microenvironment, immune cells infiltration, and drug sensitivity of CCAN in pan-cancer. MRNA expression profiles were collected from the cancer genome atlas, oncomine and ccle, the differential expression and various relevance analysis were performed with R or Perl.

Results: The results showed that the expression of CCAN was different in 33 tumors. Intriguingly, the poor survival in adrenocortical carcinoma, cholangiocarcinoma, kidney chromophobe, mesothelioma, kidney renal clear cell carcinoma, brain lower grade glioma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, thyroid carcinoma, uveal melanoma was most likely related to the kegg single transduction pathway including one carbon pool by folate, proteasome, arachidonic acid metabolism and so on. CENPC, ITGB3BP, APITD1, CENPU, and CENPW were more involved in tumor microenvironment, which more likely related to NK cells resting, T cells follicular helper, T cells CD8, neutrophils, macrophages M0, T cells CD4 memory activated. The relationship of CCAN expression with drug sensitivity showed that chelerythrine, nelarabine, and hydroxyurea maybe be potential drugs.

Conclusions: This multidimensional study provides a valuable resource to assist mechanism research and clinical utility about CCAN.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

In plain English

This was a computer analysis of public cancer databases, not a study of asbestos exposure. The authors examined 17 genes of the constitutive centromere associated network (CCAN), a group of proteins involved in cell division, across 33 tumor types from The Cancer Genome Atlas. They also used other databases of gene activity, tumor protein levels and cancer cell lines. Mesothelioma was one of the 33 tumor types, with 86 cancer cases and no normal samples. In survival analysis, most CCAN genes were described as high risk genes in ten cancer types, including mesothelioma. The exceptions were CENPC, CENPM, CENPP, CENPT, CENPU and CENPX. The authors reported 74 shared pathways linked to CCAN gene activity, few mutations, and links with particular immune cell types. They found 632 drugs associated with the genes, including chelerythrine, nelarabine and hydroxyurea. The authors concluded that CCAN might serve as a diagnostic or prognostic biomarker or a treatment target. They noted incomplete protein data and suggested lower protein than gene activity levels might reflect a small sample size or protein amounts changing during cell division.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatics analysis of publicly available cancer databases (The Cancer Genome Atlas through UCSC Xena, Oncomine, Human Protein Atlas, the Cancer Cell Line Encyclopedia, CellMiner). The analyses covered gene activity, survival, pathways, mutations, copy number changes, immune cells and drug sensitivity.
• Who was studied: Database tumor samples from 33 cancer types in The Cancer Genome Atlas. Mesothelioma (MESO) was one of them, with 86 cancer cases and 0 normal cases.
• Exposure: No asbestos or other environmental exposure was studied. The study examined the expression (activity) of 17 CCAN genes.
• Main results:
  • Across the tumor samples, CENPW, CENPH, CENPA, CENPU and CENPM formed a high expression group. These genes were strongly expressed in several cancers, including breast, uterine, lung and liver cancers.
  • The tumor-versus-normal comparison shown gene by gene excluded cancer types with fewer than 5 normal samples. Mesothelioma, which had no normal samples, therefore had no such comparison.
  • In Cox regression analysis, most CCAN genes were high risk genes in adrenocortical carcinoma, cholangiocarcinoma, kidney chromophobe, mesothelioma, brain lower grade glioma, kidney renal clear cell carcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, thyroid carcinoma and uveal melanoma. The exceptions were CENPC, CENPM, CENPP, CENPT, CENPU and CENPX.
  • Combining all CCAN genes and their significantly related pathways gave 74 shared (intersection) pathways.
  • Across the 33 cancers, CCAN genes rarely changed the overall mutation rate. Mutations were mainly concentrated in colon adenocarcinoma, rectum adenocarcinoma and uterine corpus endometrial carcinoma.
  • Across all cancers combined, the low-expression CCAN genes were mainly related to resting NK cells, T follicular helper cells, CD8 T cells, neutrophils, M0 macrophages and activated memory CD4 T cells.
  • In the CellMiner database, 632 drugs were associated with the 17 CCAN genes. The drugs with the highest correlations included chelerythrine, nelarabine and hydroxyurea.
• The authors' conclusion: The authors concluded that their analysis revealed the possibility of CCAN as a diagnostic or prognostic biomarker or a therapeutic target in the future.
• Limitations the authors state:
  • Protein data were incomplete for some genes and cancer types.
  • Expression at the protein level was lower than at the mRNA level. The authors offered a small sample size as one possible explanation, alongside protein amounts changing with the needs of cell division, and said this needs further study.
  • The authors said the dependence between CCAN and tumor immune cell infiltration needs further exploration.
  • The authors said further problems remain to be explored, such as the mismatch between protein and mRNA expression.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Tumor Microenvironment, Carcinoma, Mesothelioma, Adenocarcinoma, Macrophage.

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