Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of experimental & clinical cancer research, 2020-11, Vol.39 (1), p.1-17, Article 242

Ort / Verlag

London: BioMed Central Ltd

Erscheinungsjahr

2020

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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-1[alpha] 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. Keywords: Lung cancer, Caspase-4, K-Ras, cMyc, Survival rate, Oncoprotein, Cell proliferation, Tumor progression