Nanopore-Peptidomics to Predict Response to Chemoradiation Therapy for Lung Cancer

Purpose/Objective(s): Despite advances in cancer detection and management, the outcome for patients with Tongue Squamous Cell Carcinoma (TSCC) has not significantly improved over the last years. It is important to identify tissue molecular biomarkers that can provide information complementary to the histopathological studies and to define its relationship with progression and survival. Materials/Methods: We retrospectively reviewed 67 patients treated with curative intent between 2004 and 2012. Oral tongue specimens were obtained from archived tissue samples of biopsy and surgery. The expression of cell cycle acceleration and proliferation markers: Cdk2, cyclin B1; and tumor suppression and apoptosis markers: p16, p27, p63, bcl2, PTEN, survivin and Daxx in the cancer cells was assessed immunohistochemically using tissue microarrays (TMAs). Its predictive value on survival and relapse was analyzed. Survival curves were estimated by the Kaplan-Meier method and the resulting curves were compared using the Log-rank test. Mean follow-up: 43.6 months (DT: 29.1). Male/Female: 35/32. Mean age: 63 years (range: 24-89). Tumor stage: I-II 44 (66%); III-IV 23 (34%). Treatment: 58 (87%) pts. were surgically treated, 20 with adjuvant radiation therapy (RT) +/chemotherapy (CT). Radical RCT: 9 pts. We used the 15% labeling index as a cutoff point in cyclin B1, 5% in CdK2, p63 and bcl2, 10% in p27, p16, PTEN, Daxx, and survivin. Results: Recurrence: 22 pts (31.4%). Disease-free survival: 37.4 months (DT: 29.25), Global survival: 43.16 months (DT: 29.53). When overall and disease-free survival curves were compared, Cdk2 marker was statistically significant for overall survival (pZ 0.034), p63 for disease-free survival (p Z 0.012) and p27 for both survival curves (pZ 0.000). The other markers showed no significance although cyclin B1 was near significance (p Z 0.098). p16 overexpression was found in 9,3% (6/65 pts.) and was not statistically significant. Conclusions: The present study shows a significant predictive value for p27, Cdk2 and p63 markers with respect to survival in TSCC. p27 is the marker with a stronger significance. Thus, those markers might be useful in order to facilitate the decision for appropriate therapy modality. Cyclin B1 could also be a useful marker and needs to be further investigated. p16 expression was low and was not a marker of favorable prognosis. Author Disclosure: A. Ruiz-Alonso: None. C. Ballestin Carcavilla: None. M. Alonso Riano: None. R. Garcia-Martin: None. M. Colmenero: None. M. Murillo: None. R. Gutierrez: None. G. Sanchez-Aniceto: None. J. Perez-Regadera: None.