Emerging role of nuclear phospholipase C-β1 in lung cancer
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Non-small cell lung cancer (NSCLC) is a highly aggressive malignancy accounting for approximately 85% of all lung cancer cases. To better understand its pathology and prognosis, this study focused on the molecular profiling of tissues and clinical outcomes derived directly from lung cancer patients. Recently, the involvement of phospholipase enzymes in cancer has been highlighted, as they are involved in crucial cellular signaling pathways. The mRNA and protein expression levels of phospholipase C (PLC) isoforms were analyzed in biopsies from NSCLC patients. Utilizing Kaplan-Meier plotter database, the prognostic role of PLCs could be assessed. Researchers identified significant changes in mRNA and protein expression levels of various PLC isoforms in patient biopsies. Notably, PLCβ1 was found to be overexpressed in every tumor sample. In addition, the use of KM-Plotter hypothesized an association between elevated PLCβ1 levels and poorer survival outcomes, emphasizing the variations due to patient-specific factors, such as tumor stage and smoking history. Immunohistochemistry performed on patient-derived samples revealed a clear contrast in protein localization. In tumor tissues, PLCβ1 was predominantly found in the nucleus, whereas in adjacent healthy tissues, it remained almost exclusively in the cytoplasm. Nuclear localization is known to be linked to cell cycle modulation; therefore, it may represent a critical event in cancer development. The study highlighted critical alterations in PLC isoforms observed within the patient population. These findings demonstrate that PLCβ1 is significantly upregulated in malignant tissues and correlates with adverse clinical outcomes. Consequently, PLCβ1 may serve as a candidate biomarker, warranting further investigation into its potential role in the management and treatment of NSCLC patients.
Ethics Approval
the study was approved by the Romagna Ethics Committee (CEROM), Approval no. 2100, 11 July 2022.CRediT authorship contribution
Ilaria Versari, investigation, data curation, formal analysis, writing - original draft, writing - review & editing. Sara Salucci, investigation, data curation, formal analysis, funding acquisition, writing - original draft, writing - review & editing. Anna Bartoletti Stella, methodology, investigation. Stefania Benini, investigation. Marco Gambarotti, investigation. Camilla Sbrighi, data curation. Paola Ulivi, data curation. Andrea Ambrosini Spaltro, investigation. Mirko Traversari, investigation. Franco Stella, conceptualization, supervision, funding acquisition. Beatrice Aramini, conceptualization, supervision, writing - review & editing. Irene Faenza, conceptualization, supervision, funding acquisition, writing - original draft, writing - review & editing. All the authors contributed substantially to this manuscript, read and approved the final manuscript.
Supporting Agencies
This research was funded by Ricerca Fondamentale Orientata (RFO), University of Bologna (to I.F. and S.S.).Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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