» Articles » PMID: 21573209

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

Abstract

Background: In 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).

Methodology: Immunohistochemistry 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.

Results: Our 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 (p(trend)<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.

Conclusions: Nuclear PTMA may serve as prognostic marker in HNSCC to determine the subset of patients that are likely to show recurrence of the disease.

Citing Articles

HE2Gene: image-to-RNA translation via multi-task learning for spatial transcriptomics data.

Chen X, Lin J, Wang Y, Zhang W, Xie W, Zheng Z Bioinformatics. 2024; 40(6).

PMID: 38837395 PMC: 11164830. DOI: 10.1093/bioinformatics/btae343.


CD44-SNA1 integrated cytopathology for delineation of high grade dysplastic and neoplastic oral lesions.

Sunny S, D R R, Hariharan A, Mukhia N, Gurudath S, G K PLoS One. 2023; 18(9):e0291972.

PMID: 37747904 PMC: 10519609. DOI: 10.1371/journal.pone.0291972.


Identification of Potential Biomarkers Using Integrative Approach: A Case Study of ESCC.

Saikia M, Bhattacharyya D, Kalita J SN Comput Sci. 2022; 4(2):114.

PMID: 36573207 PMC: 9769493. DOI: 10.1007/s42979-022-01492-4.


First Evidence of the Expression and Localization of Prothymosin α in Human Testis and Its Involvement in Testicular Cancers.

Venditti M, Arcaniolo D, De Sio M, Minucci S Biomolecules. 2022; 12(9).

PMID: 36139050 PMC: 9496091. DOI: 10.3390/biom12091210.


Overexpression of prothymosin-α in glioma is associated with tumor aggressiveness and poor prognosis.

Kumar A, Kumar V, Arora M, Kumar M, Ammalli P, Thakur B Biosci Rep. 2022; 42(4).

PMID: 35297481 PMC: 9069441. DOI: 10.1042/BSR20212685.


References
1.
Warnakulasuriya S . Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2008; 45(4-5):309-16. DOI: 10.1016/j.oraloncology.2008.06.002. View

2.
Wu C, Shiau A, Lin C . Prothymosin alpha promotes cell proliferation in NIH3T3 cells. Life Sci. 1997; 61(21):2091-101. DOI: 10.1016/s0024-3205(97)00882-5. View

3.
Shiwa M, Nishimura Y, Wakatabe R, Fukawa A, Arikuni H, Ota H . Rapid discovery and identification of a tissue-specific tumor biomarker from 39 human cancer cell lines using the SELDI ProteinChip platform. Biochem Biophys Res Commun. 2003; 309(1):18-25. DOI: 10.1016/s0006-291x(03)01520-1. View

4.
Rodriguez P, Vinuela J, Alvarez-Fernandez L, Buceta M, Vidal A, Dominguez F . Overexpression of prothymosin alpha accelerates proliferation and retards differentiation in HL-60 cells. Biochem J. 1998; 331 ( Pt 3):753-61. PMC: 1219414. DOI: 10.1042/bj3310753. View

5.
Orre R, Cotter 2nd M, Subramanian C, Robertson E . Prothymosin alpha functions as a cellular oncoprotein by inducing transformation of rodent fibroblasts in vitro. J Biol Chem. 2000; 276(3):1794-9. DOI: 10.1074/jbc.M008560200. View