The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma
Pleckstrin homology domain family A (PHLDA) genes play important roles in cancer cellular processes, including inhibiting Akt activation, repressing growth factor signaling, inhibiting the negative feedback of EGFR/ErbB2 signaling cells, and inducing apoptosis. However, the prognostic significance o...
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Published in | Journal of thoracic disease Vol. 13; no. 2; pp. 689 - 707 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
China
AME Publishing Company
01.02.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Pleckstrin homology domain family A (PHLDA) genes play important roles in cancer cellular processes, including inhibiting Akt activation, repressing growth factor signaling, inhibiting the negative feedback of EGFR/ErbB2 signaling cells, and inducing apoptosis. However, the prognostic significance of PHLDA in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MM) remains unclear. The present study investigates the associations between PHLDA expression patterns and their prognostic value in lung adenocarcinoma (LUAD) and MM.
We analyzed PHLDA family members at the genomic level
to explore their mRNA expression pattern and predictive significance in LUAD and MM. We then created a PHLDA-drug interaction network and a protein-protein interaction (PPI) network using different databases. Finally, we immunohistochemically assessed the protein expression of each PHLDA family member on tissue microarrays (TMAs) in both LUAD and MM cohorts with long-term follow-up.
While
mRNA expression in both LUAD and MM was lower than that of normal tissue,
mRNA was significantly overexpressed in LUAD, and
mRNA was overexpressed in MM. In NSCLC, both low
mRNA expression and high
mRNA expression correlated with worse overall survival (OS) (P<0.01), whereas high
mRNA expression was associated with better OS (P<0.01). In MM, patients presenting high
and
mRNA expression had poor OS (P=0.01 and P<0.01, respectively). In addition, the PHLDA-drug interaction network indicated that several common drugs could potentially modulate PHLDA expression, and the PPI network suggested that
interacts with Notch family members, whereas
interacts with TP53. Our results also showed that the expression of PHLDA2 and PHLDA3 was significantly higher in LUAD and MM than that of PHLDA1 (P<0.05) and was associated with the risk of death. While patients with PHLDA2 >85.09 cells/mm
had a low risk of death (P=0.01) and a median survival time of 48 months, those with PHLDA3 <70.38 cells/mm
had a high risk of death (P=0.03) and a median survival time of 34 months.
We shed light on the role of the PHLDA family as promising predictive biomarkers and potential therapeutic targets in LUAD and MM. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Contributions: (I) Conception and design: MA Nagai, VL Capelozzi; (II) Administrative support: VL Capelozzi; (III) Provision of study materials or patients: M Balancin, AM Ab’Saber, LB Yaegashi, PC Souza, TY Takagaki; (IV) Collection and assembly of data: CM Baldavira, J Machado-Rugolo, TG Prieto, DR Bastos; (V) Data analysis and interpretation: CM Baldavira, J Machado-Rugolo, TG Prieto, DR Bastos; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. ORCID: 0000-0002-5364-7305. |
ISSN: | 2072-1439 2077-6624 |
DOI: | 10.21037/jtd-20-2909 |