Abstract
X-ray repair cross-complementing group 1 (XRCC1) is a major DNA repair gene that is responsible for fixing DNA base damage and single-strand breaks by interacting with DNA components at the damage site. This study explored the clinical significance of XRCC1 in human clear cell renal cell carcinoma (ccRCC) and further examined the mechanism of the role of XRCC1 in ccRCC. The clinical relevance of XRCC1 in ccRCC was evaluated using tissue microarrays and immunohistochemical staining of two independent human ccRCC cohorts. Our data demonstrated that XRCC1 expression was dramatically decreased in ccRCC tissues compared with that in normal renal tissues and paired adjacent non-tumor tissues. Low XRCC1 expression was significantly correlated with lymph node metastasis and with worse overall and disease-specific survival in patients, as determined by log-rank tests. However, Cox regression analysis revealed that XRCC1 expression was not an independent prognostic factor in ccRCC patients. Furthermore, XRCC1 suppressed ccRCC migration and invasion by inhibiting MMP-2 and MMP-9 expression through the regulation of TIMP-2 and TIMP-1. These findings indicated that decreased XRCC1 expression was associated with lymph node metastasis but was not an independent prognostic factor in ccRCC patients. XRCC1 may serve as a potential therapeutic target for inhibiting ccRCC metastasis but cannot be used as an independent prognostic factor.
Highlights
The most common urological tumor in adults is renal cell carcinoma (RCC), which accounts for approximately 3% of human malignancies worldwide [1]
We found that the expression of X-ray repair cross-complementing group 1 (XRCC1) was significantly lower in the clear cell renal cell carcinoma (ccRCC) samples than in the paired normal tissues (P
Our results showed that the expression of both tissue inhibitors of matrix metalloproteinases (TIMPs)-2 and TIMP-1 decreased when matrix metalloproteinase (MMP)-2 and MMP-9 were up-regulated following XRCC1 knockdown (Figure 4A), which indicated that XRCC1 can regulate MMP-2 and MMP-9 expression through TIMP-2 and TIMP-1 in ccRCC
Summary
The most common urological tumor in adults is renal cell carcinoma (RCC), which accounts for approximately 3% of human malignancies worldwide [1]. Clear cell renal cell carcinoma (ccRCC) accounts for 85%~90% of all RCC cases and has the worst prognosis of any RCC type, due to local recurrence and distant metastasis [2]. The role of XRCC1 in tumors is contradictory; low expression levels of XRCC1 were observed in gastric and pancreatic cancer and were related to invasiveness [6, 7], but a high expression of XRCC1 was observed in head and neck squamous cell carcinoma and was related to a worse patient prognosis [8]. Little is known about the role of XRCC1 in ccRCC
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