The prognostic and immunological effects of ZBTB7C across cancers: friend or foe?

Our plain-English summary of The prognostic and immunological effects of ZBTB7C across cancers: friend or foe?, by X. Chen, Z. Jiang, Z. Wang, et al (Aging, 2021).

The study

• Authors: X. Chen, Z. Jiang, Z. Wang, Z. Jiang
• Journal: Aging
• Published: 2021;13(9):12849-12864
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

As an important transcription factor, zinc-finger and BTB domain-containing 7B (ZBTB7C) plays an important role in a variety of tumors. However, its relationship with human immunity is unclear. This article aims to study its differential expression and survival across cancers and explore the relationships between its differential expression and the tumor microenvironment and immune cell infiltration. In this study, we used R software to process The Cancer Genome Atlas (TCGA) data and explored the expression pattern and prognostic value of ZBTB7C across cancers. Next, we comprehensively explained the important role of ZBTB7C in several tumor types in terms of tumor mutational burden (TMB), microsatellite instability (MSI) and immune cell infiltration. In general, the expression level of ZBTB7C in tumor tissues was lower than that in normal tissues. Highly expressed ZBTB7C was beneficial to the survival of patients with colon adenocarcinoma (COAD), lymphoid neoplasm diffuses large B cell lymphoma (DLBC), esophageal carcinoma (ESCA) and mesothelioma (MESO). Multivariate analysis showed that the expression of ZBTB7C was an independent prognostic factor in COAD and MESO. In COAD, the expression of ZBTB7C was positively correlated with both TMB and MSI. In colorectal cancer (CRC), there was a significant positive correlation between ZBTB7C expression and immune cell infiltration, especially the infiltration of mast cells and B cells. In conclusion, ZBTB7C can be used as a potential therapeutic target across cancers and is related to immune cell infiltration.

In plain English

This laboratory and database study looked at a gene called ZBTB7C across 33 cancer types. It did not study asbestos or any asbestos exposure. The authors used public Cancer Genome Atlas data (10,327 tumor and 730 noncancerous tissues) to compare gene activity in tumors and normal tissue and its link to survival. Overall, most tumor tissues had lower ZBTB7C levels than adjacent normal tissue. In four cancers, including mesothelioma, gene levels were linked to overall survival, and low levels went with poorer prognosis. After adjusting for other factors, higher ZBTB7C levels in mesothelioma went with a lower risk of death (hazard ratio 0.44; 95% confidence interval 0.24 to 0.78). The article does not say how many mesothelioma patients were included or whether their tumors were pleural or peritoneal. It also tested links with tumor mutational burden and microsatellite instability across cancers; the immune-cell and laboratory work focused on colorectal cancer, using 17 and 20 tissue pairs from one hospital in Chongqing, China. The authors concluded that ZBTB7C can be used as a biomarker of prognosis across cancers.

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: Bioinformatic pan-cancer analysis of public gene-expression, mutation and clinical databases, plus a laboratory check (RT-qPCR and immunohistochemistry) on colorectal cancer tissue samples
• Who was studied: The Cancer Genome Atlas data on 33 tumor types: 10,327 tumor tissues and 730 noncancerous tissues. There were 698 colorectal cancer patients for the immune analysis. A further 17 pairs of fresh colorectal cancer and adjacent tissue (January to June 2020) and 20 pairs of paraffin sections (June 2018 to March 2019) came from the First Affiliated Hospital of Chongqing Medical University, China. The number of mesothelioma cases is not reported.
• Exposure: No asbestos or occupational exposure was studied. The factor examined was the expression level of the ZBTB7C gene in tumor tissue. It was compared with survival, tumor mutational burden, microsatellite instability and immune cell infiltration.
• Main results:
  • Across cancers, most tumor tissues had significantly lower ZBTB7C expression than adjacent tissues.
  • ZBTB7C expression was significantly correlated with overall survival in four cancers: colon adenocarcinoma (P = 0.006), diffuse large B-cell lymphoma (P = 0.001), esophageal carcinoma (P = 0.031) and mesothelioma (P = 0.001). Low expression indicated a poor prognosis.
  • In the multivariate analysis, ZBTB7C expression was an independent prognostic factor in mesothelioma (hazard ratio = 0.44; 95% CI, 0.24 to 0.78; P = 0.006).
  • ZBTB7C expression was also an independent prognostic factor in colon adenocarcinoma (hazard ratio = 0.60; 95% CI, 0.39 to 0.94; P = 0.025).
  • The multivariate analyses for diffuse large B-cell lymphoma and esophageal carcinoma were negative.
  • Across cancer types, ZBTB7C expression was correlated with tumor mutational burden and microsatellite instability. Five tumor types (COAD, SARC, SKCM, PRAD and BRCA) were related to both, with the same trend.
  • In 698 colorectal cancer patients, ZBTB7C was positively correlated with 12 kinds of immune cells and negatively correlated with 2 kinds.
  • In the hospital colorectal cancer samples, levels of ZBTB7C and of mast cell and B cell markers were lower in cancer tissue than in adjacent normal tissue.
• The authors' conclusion: The authors concluded that ZBTB7C can be used as a biomarker of prognosis across cancers. They also concluded that it plays an important role in recruiting and regulating infiltrating immune cells in colorectal cancer.
• Limitations the authors state:
  • The immune profile was studied only in colorectal cancer, so the conclusions cannot be applied directly to all cancers.
  • More basic experiments are needed to determine the effects of ZBTB7C on metabolism and immunity.
  • Tumor progression may also change the role of the immune microenvironment.

Topics

Medical terms in this study, explained in our Lexicon: Tumor Microenvironment, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI-H), Adenocarcinoma, Neoplasm, Carcinoma, Mesothelioma, Multivariate Analysis.

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