Journal Article

Identification of a novel subpopulation of Caspase-4 positive non-small cell lung Cancer patients

Curcio, Carlo, Zito Marino, Federica, Colarusso, Chiara, Panico, Luigi, Salvi, Rosario, Terlizzi, Michela, Sorrentino, Rosalinda, De Rosa, Ilaria, Pinto, Aldo, Aquino, Rita P., Somma, Pasquale, Botti, Gerardo

2020

Overview

Background Therapy/prognosis of Non-Small Cell Lung Cancer (NSCLC) patients are strongly related to gene alteration/s or protein expression. However, more than 50% of NSCLC patients are negative to key drugable biomarkers. Methods We used human samples of NSCLC and mouse models of lung adenocarcinoma. Results We showed that caspase-4 was highly present in the tumor mass compared to non-cancerous human tissues. Interestingly, the orthologue murine caspase-11 promoted lung carcinogenesis in mice. Carcinogen-exposed caspase-11 knockout mice had lower tumor lesions than wild type mice, due to the relevance of caspase-11 in the structural lung cell as demonstrated by bone marrow transplantation and adoptive transfer experiments. Similarly to what observed in mice, caspase-4 was correlated to the stage of lung cancer in humans in that it induced cell proliferation in a K-Ras, c-MyC and IL-1α dependent manner. Caspase-4 positive adenocarcinoma (79.3%) and squamous carcinoma (88.2%) patients had lower median survival than patients who had lower levels of caspase-4. Moreover, PD-L1 expression and gene mutation (i.e. EGFR) were not correlated to caspase-4 expression. Instead, NSCLC patients who had K-Ras or c-MyC gene alteration were positively correlated to higher levels of caspase-4 and lower survival rate. Conclusions We identified a subgroup of NSCLC patients as caspase-4 positive among which double and triple positive caspase-4, K-Ras and/or c-MyC patients which prognosis was poor. Because K-Ras and c-MyC are still undrugable, the identification of caspase-4 as a novel oncoprotein could introduce novelty in the clinical yet unmet needs for NSCLC patients.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Animal experimentation / Antibodies / Apoptosis / Biomedical and Life Sciences / Biomedicine / Bone marrow transplantation / Cancer Research / Caspase-4 / cMyc / Comparative analysis / Cytokines / Development and progression / EDTA / Experiments / Gene mutation / Immunology / K-Ras / Laboratory animals / Lung cancer / Mutation / Non-small cell lung cancer / Oncology / Oncoprotein / Pathogens / Pharmacy / Polymerase chain reaction / Small cell lung cancer / Survival rate / Thermal cycling / Transplants & implants