Data mining analysis of the PP2A cell cycle axis in mesothelioma patients

Our plain-English summary of Data mining analysis of the PP2A cell cycle axis in mesothelioma patients, by R. Pippa, S. Boffo, M.D. Odero, et al (Journal of Cellular Physiology, 2020).

The study

• Authors: R. Pippa, S. Boffo, M.D. Odero, A. Giordano
• Journal: Journal of Cellular Physiology
• Published: 2020;235(6):5284-5292
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma is an aggressive tumor that affects thousands of people every year. The therapeutic options for patients are limited; hence, a better understanding of mesothelioma biology is crucial to improve patient survival. To find new molecular targets and therapeutic strategies related to the protein phosphatase 2A (PP2A) network, we analyzed the gene expression of known PP2A inhibitors in mesothelioma patient samples. Our analysis disclosed a general overexpression of all PP2A-negative regulators in mesothelioma patients. Moreover, the expression of ANP32E and CIP2A genes, increased in 16% and 11% of cases, positively correlates with the ones of all the other PP2A regulators and the ones of the main cyclins and CDKs, suggesting the existence of a feed-forward loop that might contribute to the mesothelioma progression via PP2A inactivation. Overall, our study indicates the existence of a strategic and targetable axis between PP2A inhibitors (ANP32E and CIP2A) and cell cycle regulators (cyclin B2/CDK1) and provides a valuable rationale for using a personalized combinational therapy approach to improve mesothelioma patient survival.

© 2019 Wiley Periodicals, Inc.

In plain English

The study used no new patients and no asbestos exposure data. The authors re-analysed two public sets of gene expression data: the Gordon set (5 normal pleura and 40 pleural mesothelioma samples) and The Cancer Genome Atlas set (87 mesothelioma samples). They examined genes that block PP2A and cell-cycle genes (cyclins and CDKs). In the Gordon set, only ARPP19, ANP32E, TIPRL and SET were significantly higher in tumours than in normal pleura. In the Atlas set, ANP32E was raised in 16% of patients and CIP2A in 11%. CDK1, CDK4 and cyclin B2 were significantly higher in tumours than in normal tissue. CIP2A and ANP32E gene expression correlated with that of other PP2A blockers and of several cyclins and CDKs. From survival curves, the authors reported that raised ANP32E plus CIP2A was a poor prognosis factor, and that adding cyclin B2 and CDK1 gave a better prognostic marker. No survival numbers appear in the text. The authors concluded that combined therapy against these targets might be a treatment approach needing testing in cell and animal studies.

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: Data mining (secondary analysis) of publicly available gene expression data sets; no new patients or samples were collected
• Who was studied: Gordon data set: 5 normal pleura samples and 40 pleural mesothelioma samples. The Cancer Genome Atlas (TCGA) data set: 87 mesothelioma tumor samples (1 from bronchus and lung, 86 from heart, mediastinum and pleura). Locations and dates of the original patients are not given.
• Exposure: Asbestos exposure was not studied. The study examined tumour gene expression of PP2A inhibitors (SET, CIP2A, PPME1, ARPP19, ANP32A, ANP32E, TIPRL) and of cyclin and CDK genes. Asbestos appears only in the introduction, where other work is cited.
• Main results:
  • In the Gordon data set, ARPP19, ANP32E, TIPRL, SET, PPME1 and ANP32A were higher in mesothelioma than in normal pleura. Only the differences for ARPP19, ANP32E, TIPRL and SET were statistically significant. No CIP2A data were available in this set.
  • In the TCGA data set, ANP32E expression was increased in 16% of patients and CIP2A in 11% of mesothelioma cases.
  • In the TCGA data set, TIPRL was increased in 23% of cases, ANP32A in 15% and ARPP19 in 15%. Some patients had low levels of these inhibitors.
  • In the TCGA data set, ANP32E and CIP2A expression positively correlated with the expression of all the other PP2A inhibitors studied.
  • Kaplan-Meier survival analysis in the TCGA patients indicated that concurrent overexpression of ANP32E and CIP2A was a poor prognosis factor. No numbers are given in the text.
  • CDK1, CDK4 and cyclin B2 mRNA levels were significantly increased in mesothelioma compared with normal tissue. Cyclin A2, cyclin B1 and CDK6 were increased in 10% of mesothelioma samples.
  • CIP2A and ANP32E gene expression correlated strongly and positively with the expression of cyclins and CDKs, particularly cyclin A, cyclin B, CDK1, CDK2, CDK4 and CDK6.
  • In survival analysis, the combined altered signature of CIP2A, ANP32E, cyclin B2 and CDK1 was described as a better prognostic marker than either pair alone. No numbers are given in the text.
• The authors' conclusion: The authors concluded that combination therapy targeting ANP32E and/or CIP2A together with the cyclin B/CDK1 complex might represent a personalized treatment approach for mesothelioma.
• Limitations the authors state:
  • The authors stated that studies in cell lines and animal models are needed to validate their hypothesis.
  • The authors indicated that analysis at the protein and phosphoprotein level would be needed to better understand these genes' role. This study measured only gene (mRNA) expression.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma.

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