RESUMO
Prognostic biomarkers for recurrence of Oral Squamous Cell Carcinoma (OSCC) are urgently needed. We aimed to independently validate a 4-gene expression signature (MMP1, COL4A1, P4HA2, THBS2) predictive of OSCC recurrence risk. Gene expression was measured using Nanostring nCounter® in 245 histologically normal surgical resection margins from 62 patients. Association between risk scores for individual patients and recurrence was assessed by Kaplan-Meier analysis. Signature performance was quantified by concordance index (CI), hazard ratio (HR) and the area under receiver operating characteristics (AUC). Risk scores for recurrence were significantly higher than recurrence-free patients (p = 9.58e-7, Welch's t-test). A solid performance of the 4-gene signature was determined: CI = 0.64, HR = 3.38 (p = 1.4E-4; log-rank test), AUC = 0.71. We showed that three margins per patient are sufficient to preserve predictive performance (CI = 0.65; HR = 2.92; p = 2.94e-3; AUC = 0.71). Association between the predicted risk scores and recurrence was assessed and showed HR = 2.44 (p = 9.6E-3; log-rank test, N = 62). Signature performance analysis was repeated using an optimized threshold (70th percentile of risks), resulting in HR = 3.38 (p = 1.4E-4; log-rank test, N = 62). The 4-gene signature was validated as predictive of recurrence risk in an independent cohort of patients with resected OSCC and histologically negative margins, and is potentially applicable for clinical decision making on adjuvant treatment and disease monitoring.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Colágeno Tipo IV/genética , Metaloproteinase 1 da Matriz/genética , Neoplasias Bucais/diagnóstico , Prolil Hidroxilases/genética , Trombospondinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Feminino , Seguimentos , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Recidiva Local de Neoplasia , Prognóstico , TranscriptomaRESUMO
Out of 78 adult laboratory and wild rats investigated for parasitic diseases, 19.23% were diagnosed positive for spontaneous Hymenolepis diminuta infection. Infection was more in laboratory rats (24%) than wild rats (10.71%). Sex wise distribution of H. diminuta infection was also higher male laboratory rats than females while wild rat females were found free from this tapeworm. Value of hemoglobin was significantly decreased in H. diminuta infected laboratory rats than controls. Significant increased plasma protein values in H. diminuta infected wild rats than uninfected wild rats were observed. Serum values of alkaline phosphatase, SGPT and SGOT were significantly increased in H. diminuta infected wild rats than uninfected wild rats and other groups. Tissue enzyme studies revealed that although there were alterations of different enzymes in non-target organs of H. diminuta infected rats, but only lipid peroxidation, acetylcholinesterase and catalase were altered in target organ intestine. On SEM, the segments of H. diminuta showed width from 1120 to 1160 µm while length ranged from 120 to 150 µm. Most of segments had vertical lining and raised border on its each side of circumference. On necropsy examination, intestines were found to contain 25-40 mm long and about 1 mm wide, 3-4 or more tapeworms in each rat. Relative weight of intestine was significantly increased in H. diminuta laboratory rats than controls. Histopathologically, intestinal lumina showed varying number of H. diminuta segments with serrated borders. Occasionally, scolex of tapeworm attached with intestinal mucosa was also seen. H. diminuta infection caused pressure atrophy, compressed and atrophied villi, degeneration and desquamation of lining epithelium cells and excessive mucin secretion in intestinal mucosa and lumina. Occasionally, eosinophilic cellular infiltration was also observed. High prevalence of H. diminuta infection in rats is matter of concern as zoonosis in contact human beings.(AU)