1. Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer
- Author
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Terlizzi, Michela, Colarusso, Chiara, De Rosa, Ilaria, De Rosa, Nicolina, Somma, Pasquale, Curcio, Carlo, Sanduzzi, Alessandro Zamparelli, Micheli, Pietro, Molino, Antonio, Saccomanno, Antonello, SALVI, ROSARIO, Aquino, Rita P., Pinto, Aldo, Sorrentino, Rosalinda, SANDUZZI ZAMPARELLI, ALESSANDRO, Terlizzi, Michela, Colarusso, Chiara, De Rosa, Ilaria, De Rosa, Nicolina, Somma, Pasquale, Curcio, Carlo, Sanduzzi, Alessandro Zamparelli, Micheli, Pietro, Molino, Antonio, Saccomanno, Antonello, Salvi, Rosario, Aquino, Rita P., Pinto, Aldo, Sorrentino, Rosalinda, and SANDUZZI ZAMPARELLI, Alessandro
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Tuberculosis ,Prognosi ,diagnosis ,Survival rate" ,"Lung cancer ,Caspase 4 ,NSCLC ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Lung cancer ,Survival rate ,non-small cell lung cancer ,COPD ,Lung ,biology ,business.industry ,Correction ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Biomarker ,Diagnosis ,biology.protein ,Biomarker (medicine) ,biomarker ,Non small cell ,prognosis ,business ,Diagnosi ,Research Paper - Abstract
Late diagnosis limits therapeutic options and survival rate of non-small cell lung cancer (NSCLC) patients. Therefore the identification of biomarkers represents an emerging medical need. A highly sensitive and specific test was developed to identify/quantify a novel/selective diagnostic biomarker for NSCLC patients, caspase-4. This test was validated by using i) plasma from 125 NSCLC patients and 79 healthy (non-pathological) subjects, ii) plasma from 139 smokers and iii) from 70 chronic-obstructive pulmonary disease (COPD) patients. Caspase-4 quantification was also assessed in the lung tumor mass of 98 paired NSCLC patients compared to 10 non-tumor lung tissues (i.e. tuberculosis). Circulating caspase-4 was detected in both healthy and NSCLC patients; however at different range values: 2.603-3.372 ng/ml for NSCLC patients (95% CI) compared to 0.3994-0.6219 ng/ml for healthy subjects (95% CI). The sensitivity of the test ranged from 97.07% to 100%; the specificity was 88.1% with a positive predictive value of 92.54%, accuracy of 95.19% and AUC of 0.971. Smokers (95% CI, 0.3947-0.6197 ng/ml) and COPD patients (95% CI, 1.703-2.995 ng/ml) showed intermediate values of circulating caspase-4. Tissue levels of caspase-4 in the tumor mass showed that 72 (72.7%) out of 99 patients were positive. More importantly, higher levels (cut-off value = 0.307 ng/ml) of caspase-4 in the tumor mass were associated to reduced overall survival (median 0.92 years) compared to NSCLC patients with lower levels (median 3.02 years). We report for the first time caspase-4 as a novel diagnostic and prognostic biomarker, opening new therapeutic perspectives for NSCLC patients.
- Published
- 2018