Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma

Our plain-English summary of Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma, by Z. Guo, L. Shen, N. Li, et al (Frontiers in Oncology, 2021).

The study

• Authors: Z. Guo, L. Shen, N. Li, X. Wu, C. Wang, Z. Gu, Z. Chen, J. Liu, W. Mao, Y. Han
• Journal: Frontiers in Oncology
• Published: 2021;11:789244
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma (MM) is a highly aggressive cancer with a poor prognosis. Despite the use of several well-known markers, the diagnosis of MM is still challenging in some cases. we applied bioinformatics to identify key genes and screen for diagnostic and prognostic markers of MM.

Methods: The expression profiles of GSE2549 and GSE112154 microarray datasets from the Gene Expression Omnibus database contained 87 cases of MM tissue and 8 cases of normal mesothelial tissue in total. The GEO2R tool was used to detect differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using DAVID Bioinformatics Resources. The DEGs protein-protein interaction networks were constructed from the STRING database. Cytoscape was used to identify significant modules and hub genes. The GEPIA database was used to explore relationships between hub genes and prognosis of MM. Immunohistochemistry was used to analyze protein expression in tissue microarrays with 47 Chinese MM tissues. Statistical analyses diagnostic and prognostic values.

Results: 346 DEGs were identified: 111 genes upregulated, and 235 downregulated. GO analysis showed that the primary biological processes of these DEGs were cell adhesion, leukocyte migration, and angiogenesis. The main cellular components included the extracellular space, extracellular exosome, and extracellular region. The molecular functions were integrin binding, heparin binding, and calcium ion binding. KEGG pathway analysis showed that DEGs are primarily involved in PPAR signaling pathway, extracellular matrix-receptor interactions, and regulation of lipolysis in adipocytes. Survival analysis showed that seven genes-AURKA, GAPDH, TOP2A, PPARG, SCD, FABP4, and CEBPA-may be potential prognostic markers for MM. Immunohistochemical studies showed that Aurora kinase A (AURKA gene encode, Aurora-A) and GAPDH were highly expressed in MM tissue in comparison with normal mesothelial tissue. Kaplan-Meier analysis confirmed a correlation between Aurora-A protein expression and overall survival but did not confirm a correlation with GAPDH. The receiver operating characteristic curves of Aurora-A protein expression suggested acceptable accuracy (AUC = 0.827; 95% CI [0.6686 to 0.9535]; p = 0.04). The sensitivity and specificity of Aurora-A were 83.33% and 77.78%, respectively.

Conclusion: Aurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for MM.

Copyright © 2021 Guo, Shen, Li, Wu, Wang, Gu, Chen, Liu, Mao and Han.

In plain English

This laboratory study sought markers to diagnose mesothelioma and predict survival. The authors reanalysed two public gene-expression datasets of pleural (42 tumors, 5 normal) and peritoneal (45 tumors, 3 normal) mesothelioma. They found 346 genes expressed differently and, using public data on 87 patients, picked seven genes linked to survival. They stained tissue from 47 mesothelioma patients at Zhejiang Cancer Hospital, China (44 peritoneal, 3 pleural; 22 recorded as asbestos-exposed), and 10 normal peritoneal samples. Aurora kinase A (Aurora-A) protein was found in 36 of 47 tumors and 2 of 10 normal samples. Patients whose tumors expressed it had significantly poorer overall survival. For distinguishing tumor from normal tissue, its reported sensitivity was 83.33% and specificity 77.78%. The accuracy figure (area under the curve) was 0.827 (95% confidence interval 0.6686 to 0.9535) in the abstract but 0.81 in the results. GAPDH protein was also higher in tumors but, unlike GAPDH gene expression in the public data, was not linked to survival. The authors concluded Aurora-A could be a diagnostic and potential prognostic marker, noting larger samples 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 reanalysis of public gene-expression datasets, followed by immunohistochemistry validation on a tissue microarray of mesothelioma specimens
• Who was studied: The study used three groups of samples:
• Public microarray datasets: 42 pleural mesothelioma samples and 5 normal pleural tissues (GSE2549, USA), and 45 peritoneal mesothelioma tissues and 3 normal peritoneal tissues (GSE112154, Italy).
• Survival screening: public data on 87 mesothelioma patients diagnosed 1999 to 2013.
• Validation: 47 mesothelioma specimens from patients diagnosed 2002 to 2020 at Zhejiang Cancer Hospital, China (44 peritoneal, 3 pleural; 18 men, 29 women; age 21 to 73; 42 epithelioid, 3 biphasic, 2 sarcomatoid). Controls were 10 normal peritoneal mesothelium samples from patients operated on for gastric or colon carcinoma.
• Exposure: Asbestos exposure was not the subject of the study. It was recorded for the 47 Chinese patients: 22 had been exposed to asbestos (20 peritoneal, 2 pleural cases). No fiber types are given.
• Main results:
  • 346 genes were differentially expressed between mesothelioma and normal mesothelial tissue in the two datasets: 111 upregulated and 235 downregulated.
  • In the public survival database, mesothelioma patients with higher gene expression of GAPDH, AURKA, TOP2A, SCD and FABP4 had worse overall survival.
  • In the 47 Chinese mesothelioma specimens, Aurora-A staining was present in 36 of 47 tumors. The text gives this as 76.7% and the table as 75.6%. Weak focal staining was seen in 2 of 10 normal peritoneal samples. Expression was significantly higher in mesothelioma (p less than 0.0001).
  • GAPDH staining was present in 44 of 47 mesothelioma samples (the text gives 97%, the table 93.6%) and in 4 of 10 normal samples. It was significantly higher in mesothelioma (p less than 0.0001).
  • In the tissue microarray, mesothelioma cases with Aurora-A protein expression had significantly poorer overall survival. GAPDH protein expression was not associated with overall survival or diagnostic accuracy.
  • For Aurora-A as a diagnostic test, the article's abstract reports an AUC of 0.827 (95% CI 0.6686 to 0.9535; p = 0.04), with sensitivity 83.33% and specificity 77.78%. The results section gives the AUC as 0.81 (p = 0.04).
  • Other proteins tested showed no statistically significant difference from normal tissue. TOPIIA was found in 9 of 47 mesothelioma samples. SCD1 was found in 42 of 47 mesothelioma samples and 8 of 10 normal samples. FABP4 was found in 6 of 47 mesothelioma samples. All mesothelioma cases were negative for CEBPA and PPARG.
• The authors' conclusion: The authors concluded that Aurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for malignant mesothelioma, and that it shows promise for this use.
• Limitations the authors state:
  • The authors state that, because mesothelioma is rare, larger samples are needed to verify the results.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Prognosis, Immunohistochemistry, Angiogenesis, Overall Survival, Biomarker.

Related studies

• Antiproliferative effect of Aurora kinase targeting in mesothelioma — S. Crispi, C. Fagliarone, et al. (2010)
• A Comprehensive Pan-Cancer Analysis Reveals Cyclin-Dependent Kinase Inhibitor 2A Gene as a Potential Diagnostic and Prognostic Biomarker in Colon Adenocarcinoma — A. Salem, S. Ahmed, et al. (2024)
• Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin — G. Ak, Y. Tada, et al. (2017)
• Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM) — K. Yoneda, F. Tanaka, et al. (2012)
• MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma — E. Sturchio, M.G. Berardinelli, et al. (2020)
• Gene Expression Analysis of Biphasic Pleural Mesothelioma: New Potential Diagnostic and Prognostic Markers — R. Bruno, A.M. Poma, et al. (2022)

Browse more research in Frontiers in Oncology, or return to medical research.