MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer

Our plain-English summary of MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer, by Y. Li, W. Tian, H. Zhang, et al (Frontiers in Oncology, 2022).

The study

• Authors: Y. Li, W. Tian, H. Zhang, Z. Zhang, Q. Zhao, L. Chang, N. Lei, W. Zhang
• Journal: Frontiers in Oncology
• Published: 2022;12:830570
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelin (MSLN) is a glycoprotein with various expression degrees in different tumors including mesothelioma, ovarian cancer, pancreatic cancer, etc. MSLN is considered to play an important role in cell survival, proliferation, and tumor progression. Although the expression of MSLN in tumors makes it a potential therapeutic target, its mechanism of action is still unclear, especially its correlation with immune cells infiltration in the tumor microenvironment has not been investigated. In this study, we detected the overexpression of MSLN in ovarian cancer using database analysis and tissue-array staining. We further evaluated the diagnostic value of MSLN and found it was associated with poor overall survival in ovarian cancer. In addition, the high expression of MSLN was significantly related to the immune-related genes and chemoresistant genes. We confirmed the overexpression of MSLN in the chemoresistant ovarian cancer cell lines. Our research suggests that MSLN participates in a variety of pathways related to the suppression of immune activation and promotion of chemoresistance, leading to a poor prognosis in ovarian cancer.

Copyright © 2022 Li, Tian, Zhang, Zhang, Zhao, Chang, Lei and Zhang.

In plain English

This laboratory and database study examined mesothelin (MSLN), a cell-surface protein also found in mesothelioma, in ovarian cancer. It focused on ovarian cancer and did not investigate asbestos exposure. The authors analyzed public gene databases (TCGA, GTEx, GEO, GEPIA2), stained a purchased tissue array of 57 ovarian cancer and 12 normal fallopian tube tissues, and compared two ovarian cancer cell lines. MSLN expression was increased in 18 tumor types, including ovarian cancer, and separated ovarian cancer from normal tissue with an AUC above 0.9. Staining showed high MSLN in several ovarian cancer types and low expression in normal tissue. High MSLN was linked to lower overall survival in endometrioid (p=0.00033) and serous (p=0.0023) cancer. By stage, the p values were 0.13, 0.14, 0.02 and 0.001 for stages 1 to 4. In the TCGA data, 129 of 190 high-MSLN and 103 of 189 low-MSLN patients had died. High MSLN went with more Th17, dendritic and NK cell infiltration. MSLN was higher in a cisplatin-resistant cell line. The authors concluded MSLN could be a target for therapy, especially immunotherapy.

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 (public database) analysis with tissue microarray immunohistochemistry and western blot of cell lines
• Who was studied: Public TCGA/GTEx data on 33 tumor types and 15776 tissues. The TCGA ovarian cancer patients were grouped as 189 with low and 190 with high MSLN. Also a purchased tissue microarray (57 ovarian cancer tissues, 12 normal fallopian tube tissues) and the ovarian cancer cell lines A2780 and A2780-DDP.
• Exposure: Not an exposure study. The study looked at mesothelin (MSLN) gene and protein expression in ovarian cancer. No asbestos or fiber exposure was studied.
• Main results:
  • In the pan-cancer database analysis, MSLN expression was increased in 18 tumor types, including ovarian serous cystadenocarcinoma.
  • In the ROC analysis, MSLN expression distinguished ovarian cancer with an AUC above 0.9.
  • On the tissue microarray, MSLN was highly expressed in several ovarian cancer types and low in normal tissues.
  • In Kaplan-Meier Plotter analyses, high MSLN expression was associated with lower overall survival in endometrioid (p=0.00033) and serous (p=0.0023) ovarian cancer.
  • By clinical stage, the survival p values for high MSLN expression were 0.13 (stage 1), 0.14 (stage 2), 0.02 (stage 3) and 0.001 (stage 4).
  • By grade, the survival p values for high MSLN expression were 0.0099 (grade 1), 0.038 (grade 2) and 0.0037 (grade 3).
  • In the TCGA ovarian cancer patients, 129 of 190 (34%) in the high-MSLN group had died, compared with 103 of 189 (27.2%) in the low-MSLN group (p=0.010).
  • In the TCGA ovarian cancer data, the high-MSLN group had more infiltration of Th17 cells, dendritic cells and NK cells.
  • On western blot, MSLN was higher in the cisplatin-resistant cell line A2780-DDP than in A2780.
• The authors' conclusion: The authors concluded that MSLN can be a key molecular target for new gene-targeted cancer therapy, especially immunotherapy. They also said it could be a research target for drug resistance in ovarian cancer, subject to further verification.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Ovarian Cancer, Mesothelin, Glycoprotein, Mesothelioma, Tumor Microenvironment, Overall Survival, Prognosis.

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