CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma

Our plain-English summary of CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma, by S. Okado, T. Kato, Y. Hanamatsu, et al (International Journal of Molecular Sciences, 2024).

The study

• Authors: S. Okado, T. Kato, Y. Hanamatsu, R. Emoto, Y. Imamura, H. Watanabe, Y. Kawasumi, Y. Kadomatsu, H. Ueno, S. Nakamura, T. Mizuno, T. Takeuchi, S. Matsui, T.F. Chen-Yoshikawa
• Journal: International Journal of Molecular Sciences
• Published: 2024;25(4)
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

In plain English

This study asked whether the activity of a gene called CHST4 is linked to survival in malignant pleural mesothelioma. The authors first analyzed gene-expression and survival data for 85 patients in a public database, The Cancer Genome Atlas, and found higher CHST4 activity linked to longer overall survival; among such genes it ranked first in one analysis and third in another. Genes linked to better survival were tied to immune functions, and genes linked to worse survival to cell division. The authors then stained tumor tissue from 23 patients who had surgery at Nagoya University Hospital, Japan. Patients with a CHST4 staining score of 7 or higher had a median survival after surgery of 107.8 months, against 38.0 months for those scoring below 7 (p = 0.044). Survival after recurrence was also longer with strong staining (p = 0.04). After adjustment for age, sex, stage, tumor type and pleural thickness, the CHST4 result did not reach statistical significance (p = 0.06). The authors concluded that CHST4 is a potential prognostic factor, and they noted the small number of cases. The study did not examine asbestos exposure.

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: Retrospective analysis of a public gene-expression database (The Cancer Genome Atlas), followed by an immunohistochemistry validation in stored surgical tumor specimens from one hospital
• Who was studied: 85 patients with malignant pleural mesothelioma in the TCGA database (81.2% male, 97.6% white). Separately, 51 patients who had extrapleural pneumonectomy or pleurectomy/decortication at Nagoya University Hospital, Japan, between April 2006 and May 2021, of whom 23 were included (19 male; 18 epithelioid, 5 biphasic)
• Exposure: No asbestos exposure data were reported. The factor studied was expression of the CHST4 gene, measured as mRNA in the TCGA data and as protein by immunostaining in the surgical specimens. The staining score ran from 0 to 8, with a cutoff of 7
• Main results:
  • In the TCGA data, the survival analysis identified 1,246 genes associated with overall survival
  • In the TCGA data, CHST4 was associated with better overall survival. In the univariate analysis its hazard ratio was 0.37 (95% CI 0.21 to 0.65; p = 0.0007), the lowest among favorable genes. In the multivariate analysis it was 0.32 (95% CI 0.17 to 0.60; p = 0.0003), third lowest, behind FOXO4 (0.22) and CACHD1 (0.31)
  • Genes linked to worse survival were enriched for cell-cycle terms (eight clusters). Genes linked to better survival were enriched for immune-related terms (five clusters)
  • CHST4 expression correlated positively with three Bindea immune-cell gene signatures and negatively with eight
  • Among the 23 surgical patients, those with a CHST4 total score of 7 or higher had a median postoperative survival of 107.8 months, against 38.0 months for those below 7 (p = 0.044)
  • Survival after recurrence was better with strong CHST4 expression (53.2 vs 14.0 months, p = 0.04). Recurrence-free survival was not significantly correlated with CHST4 expression
  • In the Cox analyses of the 23 surgical patients, strong CHST4 expression did not reach statistical significance: univariate hazard ratio 0.23 (95% CI 0.05 to 1.07; p = 0.06), multivariate hazard ratio 0.12 (95% CI 0.01 to 1.15; p = 0.06). In the multivariate analysis only pathological stage was significant (HR 3.06; 95% CI 1.48 to 6.33; p = 0.003). In the univariate analysis only pleural thickness was significant (HR 1.02; 95% CI 1.01 to 1.04; p = 0.01)
• The authors' conclusion: The authors concluded that CHST4 expression intensity is a potential postoperative prognostic factor in malignant pleural mesothelioma and can possibly be used to predict postoperative prognosis
• Limitations the authors state:
  • The number of cases was limited
  • Excluding patients with Grade 3 or higher complications further reduced the number of cases
  • Response to immunotherapy could not be statistically evaluated, because only 6 of the 23 patients received it and their treatments differed
  • The survival difference between the gene-based clusters may involve overfitting bias, because the clusters were built and tested on the same data
  • CHST4 is not specifically expressed in mesothelioma, and its use is limited to cases already definitively diagnosed

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Prognosis, Overall Survival, Biomarker.

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