GJB3: a comprehensive biomarker in pan-cancer prognosis and immunotherapy prediction

Our plain-English summary of GJB3: a comprehensive biomarker in pan-cancer prognosis and immunotherapy prediction, by J. Zeng, X. Li, Y. Zhang, et al (Aging, 2024).

The study

• Authors: J. Zeng, X. Li, Y. Zhang, B. Zhang, H. Wang, S. Bao, L. Zu, H. Zhang, Y. Cheng, Q. Tang, X. Xu, S. Xu, Z. Song
• Journal: Aging
• Published: 2024;16(9):7647-7667
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: A wide range of connexins are situated between normal-normal cells, cancer-cancer cells, and cancer-normal cells. Abnormalities in connexin expression are typically accompanied by cancer development; however, no systematic studies have examined the role of Gap Junction Protein Beta 3 (GJB3) in the context of tumor progression and immunity, especially when considering a broad range of cancer types.

Methods: In this study, data on GJB3 expression were gathered from Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas databases. Then, we analyzed the relationship between GJB3 expression and tumor characteristics. In vitro experiments using colony formation, EdU, CCK8, transwell migration assays, immunohistochemistry and western blot were performed to investigate the function of GJB3 in tumor progression of various cell lines. A drug sensitivity analysis of GJB3 was performed using the Genomics of Drug Sensitivity in Cancer database.

Result: Our findings demonstrate that GJB3 is widely expressed in various cancers and correlates significantly with disease stages, patient survival, immunotherapy response, and pharmaceutical guidance. Additionally, GJB3 plays a role in different cancer pathways, as well as in different immune and molecular subtypes of cancer. Co-expression of GJB3 with immune checkpoint genes was observed. Further experiments showed that knockdown of GJB3 inhibited the PI3K/AKT pathway and resulted in reduced proliferation, migration, and viability of different cancer cells.

Conclusion: Overall, GJB3 shows potential as a molecular biomarker and therapeutic target for various cancers, particularly lung adenocarcinomas, mesothelioma, pancreatic adenocarcinoma. Thus, GJB3 may represent a new therapeutic target for a wide range of cancers.

In plain English

This laboratory and database study did not examine asbestos or any occupational or environmental exposure. It looked at a gene called GJB3 (connexin 31) across 33 cancer types, including mesothelioma, using public gene-expression databases. The authors reported that GJB3 expression was increased in most cancer types compared with normal tissue. Higher GJB3 expression was associated with shorter overall survival in several cancers, including mesothelioma, lung adenocarcinoma and pancreatic adenocarcinoma. Higher GJB3 levels were associated with longer survival in breast cancer, acute myeloid leukemia and thyroid cancer. The written text gives no hazard ratio values or patient numbers for these survival analyses; hazard ratios were shown in forest plots. In cell experiments, reducing GJB3 in lung adenocarcinoma, pancreatic and mesothelioma (H2452) cell lines significantly reduced the cells' growth and migration. It also lowered activity of the PI3K/AKT growth-signaling pathway. The authors concluded that GJB3 typically predicts a poor outcome in various cancers, especially these three. They noted that it remains uncertain whether GJB3 directly affects survival through the immune response, and that more clinical and experimental data are needed.

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 public cancer and normal-tissue databases (TCGA, GTEx, CCLE, GDSC), combined with laboratory experiments on cancer cell lines and immunohistochemistry of tissue samples
• Who was studied: Database data on 33 cancer types, including mesothelioma (MESO). Cell lines: lung adenocarcinoma (H2030, DV90), pancreatic adenocarcinoma (PANC1) and mesothelioma (H2452). Melanoma tissue microarrays. Six paired tumor and adjacent lung tissues from lung adenocarcinoma patients at Tianjin Medical University General Hospital, China
• Exposure: No asbestos, fiber, occupational or environmental exposure was studied. The factor examined was the expression level of the GJB3 gene and the effect of reducing it in cells with small interfering RNA. A database analysis also correlated GJB3 expression with drug sensitivity in lung adenocarcinoma cell lines.
• Main results:
  • GJB3 expression was increased in the majority of cancer types in matched tumor versus normal tissue comparisons (the listed types did not include mesothelioma)
  • In Kaplan-Meier analyses, high GJB3 expression was associated with shorter overall survival in KIRC, LUAD, LIHC, PAAD and MESO, and with longer overall survival in BRCA, LAML and THCA (no numerical values given in the written text)
  • In Cox regression, high GJB3 expression was associated with shorter overall survival in LUAD, PAAD, MESO, SKCM, LIHC, THYM and ACC. The hazard ratios were shown in forest plots, not in the written text.
  • High GJB3 expression was associated with worse disease-specific survival and progression-free interval in GBM, KIRC, LUAD, MESO and PAAD
  • Immunohistochemistry showed higher GJB3 levels in lung adenocarcinoma and skin melanoma tissue than in non-cancerous tissue
  • GJB3 knockdown significantly reduced growth of the lung adenocarcinoma cell lines DV90 and H2030
  • In the pancreatic (PANC1) and mesothelioma (H2452) cell lines, GJB3 knockdown significantly reduced proliferation and migration
  • In H2030, PANC1 and H2452 cells, GJB3 knockdown significantly suppressed phosphorylated PI3K and AKT
  • In lung adenocarcinoma cell lines, of 17 drugs evaluated, sensitivity to 10 correlated positively and to 7 negatively with GJB3 expression
• The authors' conclusion: The authors concluded that GJB3 is abnormally expressed and typically predicts a poor outcome in various cancers, especially lung adenocarcinoma, pancreatic adenocarcinoma and mesothelioma, and may be a promising novel immune target
• Limitations the authors state:
  • It remains uncertain whether GJB3 directly affects patient survival through the immune response
  • Additional clinical and experimental data are needed to validate the biological processes and molecular mechanisms

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Prognosis, Immunotherapy, Immunohistochemistry, Lung Adenocarcinoma, Mesothelioma, Adenocarcinoma.

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