Overexpression of Prothymosin Alpha Predicts Poor Disease Outcome in Head and Neck Cancer

Abstract

BackgroundIn our recent study, tissue proteomic analysis of oral pre-malignant lesions (OPLs) and normal oral mucosa led to the identification of a panel of biomarkers, including prothymosin alpha (PTMA), to distinguish OPLs from histologically normal oral tissues. This study aimed to determine the clinical significance of PTMA overexpression in oral squamous cell hyperplasia, dysplasia and head and neck squamous cell carcinoma (HNSCC).MethodologyImmunohistochemistry of PTMA protein was performed in HNSCCs (n = 100), squamous cell hyperplasia (n = 116), dysplasia (n = 50) and histologically normal oral tissues (n = 100). Statistical analysis was carried out to determine the association of PTMA overexpression with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients.ResultsOur immunohistochemical analysis demonstrated significant overexpression of nuclear PTMA in squamous cell hyperplasia (63.8%), dysplasia (50%) and HNSCC (61%) in comparison with oral normal mucosa (ptrend<0.001). Chi-square analysis showed significant association of nuclear PTMA with advanced tumor stages (III+IV). Kaplan Meier survival analysis indicated reduced disease free survival (DFS) in HNSCC patients (p<0.001; median survival 11 months). Notably, Cox-multivariate analysis revealed nuclear PTMA as an independent predictor of poor prognosis of HNSCC patients (p<0.001, Hazard's ratio, HR = 5.2, 95% CI = 2.3–11.8) in comparison with the histological grade, T-stage, nodal status and tumor stage.ConclusionsNuclear PTMA may serve as prognostic marker in HNSCC to determine the subset of patients that are likely to show recurrence of the disease.

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

“…These Wndings support the potential usage of proT as a diagnostic tool, maybe also as a therapeutic target, for cancers of the urinary tract. Finally, immunostaining of hepatocellular carcinomas [60], pituitary tumors [61] and head and neck carcinomas [62], but not of gastric cancers [63], associated high proT content with aggressive tumors and poor prognosis. As proT is an intracellular protein, studies to reveal its relevance to cancer were performed until recently in malignant tissues and their extracts.…”

“…Subsequent complementary research investigated proT expression in human bladder cancer using tissue microarrays [58]. A statistically signiWcant enhancement of proT expression, also from the clinical aspect, was Colon mRNA in tissue c-myc expression [45,52] Gastric Protein in tissue - [63] Head and neck Protein in tissue Tumor recurrence [62] Liver mRNA in tissue; protein in tissue c-myc expression; poor prognosis [46,60] Lung mRNA in tissue Poor prognosis [48] Neuroblastoma mRNA in tissue N-myc expression [47] Pituitary Protein in tissue Tumor recurrence [61] Prostate Protein in tissue Cancer cell diVerentiation; tumor progression [56,57] Rectal mRNA in tissue EVectiveness of radiotherapy [51] Rhabdomyosarcoma mRNA in tissue - [49] Thyroid mRNA in tissue; protein in tissue and serum…”

Transglutaminase 2 Overexpression in Tumor Stroma Identifies Invasive Ductal Carcinomas of Breast at High Risk of Recurrence

“…Serial paraffin embedded tissue sections (4 µm thickness) were deparaffinized in xylene, hydrated through graded alcohol series, pre-treated in a microwave oven for 15 min in Tris-EDTA (0.1 M, pH = 9.0) containing Tween 20 (0.05% v/v) for antigen retrieval [31]. Slides were washed with Tris-buffered saline (TBS, 0.1 M, pH = 7.2) containing Triton X-100 (0.1%) followed by treatment with 0.3% H 2 O 2 at room temperature for 10 minutes to block the endogenous peroxidase activity.…”

Characterization of two thymosins as immune-related genes in common carp (Cyprinus carpio L.)

“…Several studies have demonstrated ProTα's function in immune regulatory activity and potentiation of the immune system (Cordero et al, 1991;Oates et al, 1988). Recent studies documented that ProTα also played a regulatory role in apoptosis because of the significance of this process in development, cell turnover, and tumorigenesis (Emmanouilidou et al, 2013;Jiang et al, 2003;Qi et al, 2010;Tripathi et al, 2011). First identified from a cytokine-like activity, Tβs play significant roles in various physiological processes.…”