DNA repair protein XPA is differentially expressed in colorectal cancer and predicts better prognosis

Abstract

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.

Keywords: XPA; Colorectal cancer; prognosis.

Figure 1

Representative photomicrographs of immunohistochemical staining of XPA in CRC specimens and adjacent nontumor specimens. (A) Colorectal cancer tissues and (B) adjacent nontumor tissues of CRC. Original magnification, ×200.

Figure 2

Different XPA expression levels in CRC tissues. (A) negative (−), (B) weakly positive (+), (C) moderately positive (++), and (D) strongly positive (+++). Magnification, ×200.

Figure 3

XPA protein expression was significantly decreased in CRC tissues compared with nontumor adjacent tissues. According to the Mann–Whitney U‐test, the differential expression of XPA between CRC specimens and nontumor adjacent specimens was visualized by scatter plots. *: P<0.05

Figure 4

High expression of XPA correlates with the prognosis in CRC patients. (A) Kaplan–Meier analysis and log‐rank test for overall survival according to XPA expression level; (B) patients over 60 years of age with high XPA expression exhibited longer survival time than those with low XPA expression; (C) rectal cancer individuals who expressed higher XPA protein demonstrated favorable prognosis; (D) subgroup without distant metastasis also identified XPA expression as a good indicator for CRC prognosis.