Dataset Information

XPA: DNA Repair Protein of Significant Clinical Importance.

ABSTRACT: 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.

SUBMITTER: Borszekova Pulzova L

PROVIDER: S-EPMC7139726 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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XPA: DNA Repair Protein of Significant Clinical Importance.

Borszéková Pulzová Lucia L Ward Thomas A TA Chovanec Miroslav M

International journal of molecular sciences 20200322 6

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 re ...[more]

PMID: 32235701

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Project description:As an indispensable factor in DNA damage recognition step of nucleotide excision repair, XPA interacts with a series of proteins to initiate repair process. The expression characteristics of XPA in colorectal cancer (CRC) and its influence on CRC prognosis remain elusive. Tissue specimens of CRC and nontumor adjacent tissues from 283 patients were collected. XPA protein expressions were detected by immunohistochemistry staining. Nonparametric test was used to investigate the difference of XPA expression between CRC and nontumor adjacent tissues, as well as the correlation between XPA expression and clinicopathological parameters of CRC. Univariate and multivariate Cox proportional hazards models were applied to estimate the relationship between XPA expression and CRC prognosis. Meanwhile, we analyzed TCGA data to investigate the relation between XPA mRNA expression and survival of CRC. XPA protein expression was significantly decreased in CRC tissues compared with nontumor adjacent tissues (P = 0.001). Subgroup analysis indicated consistently significant down-regulation of XPA in CRC tissues in age > 60 (P = 0.026), age ≤ 60 (P = 0.008), colon cancer (P = 0.009), and rectal cancer (P = 0.015) patients and males (P = 0.004). For clinicopathological parameters, CRC patients with drinking habits revealed XPA overexpression than nondrinkers (P = 0.032). For prognosis, CRC patients with high XPA protein expression had longer overall survival (OS) (HR = 0.62, 95%CI: 0.39-0.97, P = 0.037). Stratified analysis suggested a better prognosis in relation to high XPA protein expression in patients over 60 years (adjusted HR = 0.48, P = 0.021), with rectal cancer (HR = 0.56, P = 0.037), without distant metastasis (HR = 0.58, P = 0.033), without tumor deposits (HR = 0.40, P = 0.006; adjusted HR = 0.44, P = 0.028), and with tumor diameter over 4 cm (HR = 0.49, P = 0.023). DNA repair protein XPA is significantly decreased in colorectal cancer tissues than in adjacent nontumor tissues. High expression of XPA protein showed significant relationship with better survival of CRC, especially rectal cancer. XPA might be a novel biomarker but might not be an independent factor to predict prognosis of CRC patients.

Dataset Information

XPA: DNA Repair Protein of Significant Clinical Importance.

Publications

XPA: DNA Repair Protein of Significant Clinical Importance.

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