Nucleotide Excision Repair Proteins and Risk of Head and Neck Squamous Cell Carcinomas in a Chinese Population

2020 ◽  
Author(s):  
Pengyu Ren ◽  
Xiaorong Niu ◽  
Ruimin Zhao ◽  
Zichen Chen ◽  
Hao Dai ◽  
...  

Abstract Background Nucleotide excision repair (NER) is pivotal in the development of smoking-related malignancies. We hypothesize that expression levels of NER proteins are associated with risk of the head and neck squamous cell carcinomas (HNSCCs) in a Chinese population. Methods To test this hypothesis, we conducted a case-control study of 337 HNSCC patients and 285 cancer-free controls by measuring the expression levels of nine core NER proteins in cultured peripheral lymphocytes. Results Compared with the controls, cases had statistically significantly lower expression levels of XPA (P=0.001). After dividing the subjects by controls’ medians of expression levels, we found an association between an increased risk of HNSCCs and low XPA expression levels [adjusted ORs and 95% CIs:1.42 and 1.03-1.96; Ptrend=0.031]. We identified a multiplicative interaction between smoking as well as drinking status and XPA expression levels (P = 0.005 and 0.044, respectively). Finally, the sensitivity of the expanded model with protein expression levels, in addition to demographic variables, on HNSCCs risk was significantly improved, especially among ever smokers and ever drinkers. Conclusions Reduced XPA expression levels were associated with an increased risk of HNSCCs in a Chinese population.

Oncotarget ◽  
2016 ◽  
Vol 8 (10) ◽  
pp. 16190-16201 ◽  
Author(s):  
Leisa Lopes-Aguiar ◽  
Ericka Francislaine Dias Costa ◽  
Guilherme Augusto Silva Nogueira ◽  
Tathiane Regine Penna Lima ◽  
Marília Berlofa Visacri ◽  
...  

Cancer ◽  
2002 ◽  
Vol 94 (2) ◽  
pp. 393-397 ◽  
Author(s):  
Lie Cheng ◽  
Erich M. Sturgis ◽  
Susan A. Eicher ◽  
Margaret R. Spitz ◽  
Qingyi Wei

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 606 ◽  
Author(s):  
Inga Grzechowiak ◽  
Justyna Graś ◽  
Dominika Szymańska ◽  
Martyna Biernacka ◽  
Kacper Guglas ◽  
...  

Background: Head and neck squamous cell carcinomas are a group of heterogeneous diseases that occur in the mouth, pharynx and larynx and are characterized by poor prognosis. A low overall survival rate leads to a need to develop biomarkers for early head and neck squamous cell carcinomas detection, accurate prognosis and appropriate selection of therapy. Therefore, in this paper, we investigate the biological role of the PTTG3P pseudogene and associated genes PTTG1 and PTTG2 and their potential use as biomarkers. Methods: Based on TCGA data and the UALCAN database, PTTG3P, PTTG1 and PTTG2 expression profiles and clinicopathological features with TP53 gene status as well as expression levels of correlated genes were analyzed in patients’ tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. Gene Set Enrichment Analysis software was used for functional enrichment analysis. All statistical analyses were performed using GraphPad Prism 5. Results: In head and neck squamous cell carcinomas, significant up-regulation of the PTTG3P pseudogene, PTTG1 and PTTG2 genes’ expression between normal and cancer samples were observed. Moreover, the expression of PTTG3P, PTTG1 and PTTG2 depends on the type of mutation in TP53 gene, and they correlate with genes from p53 pathway. PTTG3P expression was significantly correlated with PTTG1 as well as PTTG2, as was PTTG1 expression with PTTG2. Significant differences between expression levels of PTTG3P, PTTG1 and PTTG2 in head and neck squamous cell carcinomas patients were also observed in clinicopathological contexts. The contexts taken into consideration included: T-stage for PTTG3P; grade for PTTG3, PTTG1 and PTTG2; perineural invasion and lymph node neck dissection for PTTG1 and HPV p16 status for PTTG3P, PTTG1 and PTTG2. A significantly longer disease-free survival for patients with low expressions of PTTG3P and PTTG2, as compared to high expression groups, was also observed. Gene Set Enrichment Analysis indicated that the PTTG3 high-expressing group of patients have the most deregulated genes connected with DNA repair, oxidative phosphorylation and peroxisome pathways. For PTTG1, altered genes are from DNA repair groups, Myc targets, E2F targets and oxidative phosphorylation pathways, while for PTTG2, changes in E2F targets, G2M checkpoints and oxidative phosphorylation pathways are indicated. Conclusions: PTTG3P and PTTG2 can be used as a prognostic biomarker in head and neck squamous cell carcinomas diagnostics. Moreover, patients with high expressions of PTTG3P, PTTG1 or PTTG2 have worse outcomes due to upregulation of oncogenic pathways and more aggressive phenotypes.


2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e17523-e17523
Author(s):  
Carla Tyene Nakata ◽  
Ericka Francislaine Dias Costa ◽  
Bruno De Araujo Lima Franca ◽  
Leisa Lopes Aguiar ◽  
Fernanda Proa Ferreira ◽  
...  

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