Associations between expression levels of nine core nucleotide excision repair genes in lymphocytes and risk of head and neck squamous cell carcinomas in a Chinese population

Ren, Pengyu; Niu, Xiaorong; Liu, Chang; Liu, Junsong; Li, Honghui; Zhao, Qian; Xing, Juanli; Bai, Yang; Liang, Yiqian; Han, Peng

doi:10.1007/s10147-019-01586-9

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…These results further support the notion that altered translational levels of NER genes, which have a more direct effect on the NER capacity than that of transcript levels, may contribute to the risk of HNSCCs. Moreover, our previous work of transcript level suggested that mRNA expression level of XPA and XPB were statistically signi cantly lower in cases than in controls, and the reduced mRNA expression levels of XPB were associated with an increased risk of HNSCCs in a Chinese population [41], however, we did not nd the above association with XPB in translational level. One reason for this discrepancy is that the transcript levels and translational levels of NER genes may not be directly correlated.…”

Section: Discussioncontrasting

confidence: 84%

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

Ren

Niu

Zhao

et al. 2020

Preprint

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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.

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Section: Discussioncontrasting

confidence: 84%

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

Ren

Niu

Zhao

et al. 2020

Preprint

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“…Statistically significantly lower XPA expression level has been found in HNSCC patients compared with controls [200]. In this malignity, no correlation between XPA expression and OS was found when looking at the overall HNSCC patient cohort.…”

Section: Xpa Expression As a Cancer Risk Factor And Its Prognostic And Predictive Valuementioning

confidence: 55%

XPA: DNA Repair Protein of Significant Clinical Importance

Pulzová¹,

Ward

Chovanec³

2020

IJMS

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The nucleotide excision repair (NER) pathway is activated in response to a broad spectrum of DNA lesions, including bulky lesions induced by platinum-based chemotherapeutic agents. Expression levels of NER factors and resistance to chemotherapy has been examined with some suggestion that NER plays a role in tumour resistance; however, there is a great degree of variability in these studies. Nevertheless, recent clinical studies have suggested Xeroderma Pigmentosum group A (XPA) protein, a key regulator of the NER pathway that is essential for the repair of DNA damage induced by platinum-based chemotherapeutics, as a potential prognostic and predictive biomarker for response to treatment. XPA functions in damage verification step in NER, as well as a molecular scaffold to assemble other NER core factors around the DNA damage site, mediated by protein–protein interactions. In this review, we focus on the interacting partners and mechanisms of regulation of the XPA protein. We summarize clinical oncology data related to this DNA repair factor, particularly its relationship with treatment outcome, and examine the potential of XPA as a target for small molecule inhibitors.

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“…These results further support the notion that altered translational levels of NER pathway, which have a more direct effect on the NER capacity than that of transcript levels, may contribute to the risks of HNSCCs. Moreover, our previous work of transcript level suggested that mRNA expression levels of XPA and XPB were statistically significantly lower in cases than in controls, and the reduced mRNA expression levels of XPB were associated with an increased risk of HNSCCs in a Chinese population [ 46 ]. However, we did not find above association with XPB in translational level.…”

Section: Discussionmentioning

confidence: 99%

Combining Phenotypes of Nucleotide Excision Repair Pathway to Predict the Risk of Head and Neck Squamous Cell Carcinomas in a Chinese Population

et al. 2022

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Background. Nucleotide excision repair (NER) is pivotal in the development of smoking-related malignancies. Nine core genes (XPA, XPB, XPC, XPD, XPF, XPG, ERCC1, DDB1, and DDB2) are highly involved in the NER process. We combined two phenotypes of NER pathway (NER protein and NER gene mRNA expression) and evaluated their associations with the risks of the head and neck squamous cell carcinomas (HNSCCs) in a Chinese population. Methods. 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 and NER gene mRNA in cultured peripheral lymphocytes. Results. Compared with the controls, cases had statistically significantly lower protein expression levels of XPA ( P < 0.001 ) and lower mRNA expression levels of XPA and XPB ( P = 0.005 and 0.001, respectively). After dividing the subjects by controls’ medians of expression levels, we found an association between increased risks of HNSCCs and low XPA protein level ( P trend = 0.031 ), as well as low mRNA levels of XPA and XPB ( P trend = 0.024 and 0.001, respectively). Subsequently, we correlated the two phenotypes and found associations between the NER mRNA and protein levels. Finally, the sensitivity of the expanded model with protein and mRNA expression levels, in addition to demographic variables, on HNSCCs risk was significantly improved. Conclusions. Combining two phenotypes of NER pathway may be more effective than the model only including one single phenotype for the assessment of risks of HNSCCs.

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Associations between expression levels of nine core nucleotide excision repair genes in lymphocytes and risk of head and neck squamous cell carcinomas in a Chinese population

Cited by 6 publications

References 37 publications

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

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

XPA: DNA Repair Protein of Significant Clinical Importance

Combining Phenotypes of Nucleotide Excision Repair Pathway to Predict the Risk of Head and Neck Squamous Cell Carcinomas in a Chinese Population

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