Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer
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Michela Terlizzi1, Chiara Colarusso1,5, Ilaria De Rosa2, Nicolina De Rosa2, Pasquale Somma2, Carlo Curcio3, Alessandro Sanduzzi4, Pietro Micheli2, Antonio Molino4, Antonello Saccomanno1, Rosario Salvi3, Rita P. Aquino1, Aldo Pinto1 and Rosalinda Sorrentino1
1Department of Pharmacy, University of Salerno, ImmunePharma S.r.l., Fisciano, SA, Italy
2Anatomy and Pathology Unit, Ospedale dei Colli, AORN, “Monaldi”, Naples, Italy
3Thoracic Surgery Unit, Ospedale dei Colli, AORN, “Monaldi”, Naples, Italy
4Department of Respiratory Medicine, Respiratory Division, University of Naples Federico II, Fisciano, SA, Italy
5PhD Program in Drug Discovery and Development, Department of Pharmacy, University of Salerno, Fisciano, SA, Italy
Rosalinda Sorrentino, email: [email protected]
Keywords: non-small cell lung cancer; NSCLC; diagnosis; prognosis; biomarker
Received: February 27, 2018 Accepted: March 17, 2018 Published: April 10, 2018
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.
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