High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma

Our plain-English summary of High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma, by G.Y. Ma, S. Shi, Y.Z. Sang, et al (BioMed Research International, 2023).

The study

• Authors: G.Y. Ma, S. Shi, Y.Z. Sang, P. Wang, Z.G. Zhang
• Journal: BioMed Research International
• Published: 2023;2023:6575194
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: To investigate the value of SMO and GLI1 genes in the hedgehog pathway in malignant mesothelioma specimens. Further study on the expression and prognosis of SMO and GLI1 in malignant mesothelioma tissues and the relationship between the two and the molecular mechanisms of mesothelioma immunity and to further investigate the prognostic value of mesothelioma expression.

Materials And Methods: Immunohistochemistry and RT-qPCR were applied to detect the expression of SMO and GLI1 proteins and mRNA in biopsy specimens and plasma cavity effusion specimens from malignant mesothelioma (n = 130) and benign mesothelial tissues (n = 50) and to analyze the clinicopathological significance and survival risk factors of SMO and GLI1 protein expression in mesothelioma. The mechanisms of mesothelioma cell expression and immune cell infiltration were investigated using bioinformatics methods.

Results: SMO and GLI1 in mesothelioma tissues detected high concordance between the diagnostic results of mesothelioma biopsy specimens and plasma cavity effusion specimens. The expression levels of SMO and GLI1 protein and mRNA in mesothelioma tissues were higher than those in benign mesothelioma tissues. The expression levels of SMO and GLI1 protein were correlated with the age, site, and asbestos exposure history of patients with mesothelioma. The expression levels of SMO and GLI1 protein were correlated with the expressions of ki67 and p53 (P < 0.05). SMO and GLI1 gene expression levels were negatively correlated with good prognosis in mesothelioma patients (P < 0.05). Cox proportional risk model indicated that protein expressions of invasion, lymph node metastasis, distant metastasis, staging, and genes were independent prognostic factors of mesothelioma. The GEPIA database showed the overall survival rate and the disease-free survival rate of mesothelioma patients in the high SMO and GLI1 expression groups; the UALCAN database analysis showed lower SMO expression levels in mesothelioma patients with more pronounced TP53 mutations (P = 0.001); GLI1 gene expression levels were strongly correlated with lymph node metastasis in mesothelioma patients (P = 0.009). Timer database analysis showed that the mechanism of immune cell infiltration was closely related to SMO and GLI1 expression. The degree of immune cell infiltration was strongly correlated with the prognosis of mesothelioma patients (P < 0.05).

Conclusion: The expression levels of both SMO and GLI1 proteins were higher than those of normal mesothelial tissues, and the mRNA expression levels also changed in the same direction. SMO and GLI1 gene expressions in mesothelioma were negatively correlated with age, site of occurrence, and history of asbestos exposure. Positive expression of SMO and GLI1 was negatively correlated with patient survival. The Cox proportional risk model showed that gender, history of asbestos exposure, site of occurrence, SMO, and GLI1 were independent prognostic factors for mesothelioma. The mechanism of immune cell infiltration in mesothelioma is closely related to the gene expression of both and the survival prognosis of mesothelioma patients.

Copyright © 2023 Guan-Ying Ma et al.

In plain English

This study from Cangzhou People's Hospital, China, examined two hedgehog-pathway genes, SMO and GLI1, in 130 patients with malignant mesothelioma (60 pleural, 70 peritoneal) treated from January 2017 to December 2021, and in 50 benign mesothelial tissues. The authors stained biopsy and body-cavity fluid specimens, measured mRNA in 30 tissue samples, and analyzed public databases. In biopsies, SMO was positive in 81.54% (106/130) of mesotheliomas versus 14.00% (7/50) of benign tissues, and GLI1 in 76.15% (99/130) versus 18.00% (9/50). SMO was positive in 81 of 85 patients with an asbestos exposure history and 25 of 45 without, although the text calls this a negative correlation. Fiber types were not reported. Over 2 to 55 months of follow-up, higher SMO and GLI1 expression was linked with poorer survival. A multivariable analysis listed SMO, GLI1, tumor site, sex and asbestos exposure history as risk factors for survival time. The authors proposed SMO, GLI1 and immune cells as possible indicators of prognosis and treatment. The article contains internal inconsistencies.

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 laboratory study of patient specimens using immunohistochemistry and RT-qPCR, with a diagnostic-test comparison of biopsy versus body-cavity effusion specimens and bioinformatics analysis of public databases (GEPIA, UALCAN, TIMER, drawing on TCGA data)
• Who was studied: 130 patients with malignant mesothelioma treated at Cangzhou People's Hospital, Hebei, China, between January 2017 and December 2021 (60 male, 70 female; 60 pleural, 70 peritoneal per Table 8), compared with 50 benign mesothelial tissues. mRNA was measured in 30 tissue specimens.
• Exposure: Asbestos exposure history recorded only as yes (85 patients) or no (45 patients). No fiber types, products, jobs or doses are reported. The main laboratory variables were SMO and GLI1 protein and mRNA expression.
• Main results:
  • In biopsy specimens, SMO was positive in 81.54% (106/130) of malignant mesotheliomas versus 14.00% (7/50) of benign mesothelial tissues.
  • In biopsy specimens, GLI1 was positive in 76.15% (99/130) of malignant mesotheliomas versus 18.00% (9/50) of benign tissues.
  • In effusion (body-cavity fluid) specimens, SMO was positive in 22.00% (11/50) of benign versus 73.08% (95/130) of mesothelioma cases. GLI1 was positive in 32.00% (16/50) versus 66.15% (86/130).
  • Of 30 mesothelioma tissues tested for mRNA, SMO was highly expressed in 28, with more than 2-fold upregulation in 24 of these. GLI1 was highly expressed in 27, with more than 2-fold upregulation in 22.
  • The text states that SMO and GLI1 protein expression was 'negatively correlated' with age, asbestos exposure history, tumor site, Ki67 and P53 (P less than 0.05). However, Table 8 shows SMO positive in 81 of 85 patients with an asbestos exposure history versus 25 of 45 without, and GLI1 positive in 73 of 85 versus 26 of 45.
  • Among the 130 patients followed for 2 to 55 months, higher SMO and GLI1 protein expression was associated with poorer survival (P less than 0.05).
  • In Cox multivariate analysis, the authors reported SMO and GLI1 expression, tumor site, sex and asbestos exposure history as risk factors for survival time. The asbestos exposure history values were 5.855 (95% CI 1.225-27.989, P 0.027) in the SMO model and 6.990 (1.656-29.512, P 0.008) in the GLI1 model. The table does not label what kind of ratio these figures are.
  • In the GEPIA public database, mesothelioma patients with high SMO expression (n = 41) had worse overall survival than those with low expression (n = 40): HR (high) = 2.1, logrank p = 0.0051.
• The authors' conclusion: The authors concluded that SMO and GLI1 expression was associated with poor prognosis and with immune cell infiltration in malignant mesothelioma. They proposed SMO, GLI1 and immune cells as possible indicators for personalized immunotherapy and prognosis.
• Limitations the authors state:
  • Diagnostic accuracy of effusion (fluid) specimens may be slightly lower because the fluid contains few cells.

Topics

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

Medical terms in this study, explained in our Lexicon: Prognosis, Malignant Mesothelioma, Mesothelioma, Immunohistochemistry, Biopsy, Asbestos Exposure, Metastasis, Staging.

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