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

Journal of Experimental & Clinical Cancer Research

Pasquale Somma¹  Luigi Panico¹  Ilaria De Rosa¹  Michela Terlizzi²  Aldo Pinto²  Chiara Colarusso²  Rosalinda Sorrentino²  Rita P. Aquino²  Federica Zito Marino³  Gerardo Botti⁴  Carlo Curcio⁵  Rosario Salvi⁵ 

[1] Anatomy and Pathology Unit, Ospedale dei Colli, AORN, “Monaldi”;Department of Pharmacy (DIFARMA), University of Salerno;Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”;Scientific Direction IRCCS National Cancer Institute “G. Pascale”;Thoracic Surgery Unit, Ospedale dei Colli, AORN, “Monaldi”;

关键词: Lung cancer;    Caspase-4;    K-Ras;    cMyc;    Survival rate;    Oncoprotein;   

DOI  :  10.1186/s13046-020-01754-0

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown