ABSTRACT
Purpose@#Apurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme involved in the base excision repair pathway. It also has redox activity and maintains various transcription factors in an active reduced state. APE1 may be associated with chemoresistance. In the present study, we first investigated the expression level of APE1 protein and its correlation with oncologic outcomes of oxaliplatin-based chemotherapy in patients with stage III colon cancer. Further, we investigated the effects of human APE1 siRNA on the sensitivity of oxaliplatin in SNU-C2A colon cancer cells. @*Methods@#Tissue specimens from tumor and normal colon of 33 patients with stage III colon cancer were obtained from 2006 to 2009. The patients received at least eight cycles of oxaliplatin-based chemotherapy. APE1 expression was analyzed by immunohistochemistry and Western blotting using a cultured SNU-C2A cell line. Cell viability and apoptosis were determined by Cell Counting Kit-8 and caspase-3 cleavage using Western blotting. @*Results@#All the colon cancer tissues showed APE1 staining in the nucleus, whereas all the normal colon tissues were negative for APE1 staining in the cytoplasm. The group with a higher expression of APE1 demonstrated poorer prognosis than the group with low expression (P=0.026 for overall survival and P=0.021 for disease-free survival). Treatment with oxaliplatin resulted in a dose-dependent increase in APE1 expression in SNU-C2A cells. APE1 siRNA significantly enhanced oxaliplatin-induced growth inhibition, and also increased oxaliplatin-induced apoptosis in SNU-C2A cells. @*Conclusion@#APE1 could be considered a prognostic factor in colon cancer patients treated with oxaliplatin-based chemotherapy.
ABSTRACT
PURPOSE: This study was conducted to discover the clinical factors that can predict pathologically complete remission (pCR) after neoadjuvant chemoradiotherapy (CRT), so that those factors may help in deciding on a treatment program for patients with locally advanced rectal cancer. METHODS: A total of 137 patients with locally advanced rectal cancer were retrospectively enrolled in this study, and data were collected retrospectively. The patients had undergone a total mesorectal excision after neoadjuvant CRT. Histologic response was categorized as pCR vs. non-pCR. The tumor area was defined as (tumor length) × (maximum tumor depth). The difference in tumor area was defined as pre-CRT tumor area – post-CRT tumor area. Univariate and multivariate logistic regression analyses were conducted to find the factors affecting pCR. A P-value < 0.05 was considered significant. RESULTS: Twenty-three patients (16.8%) achieved pCR. On the univariate analysis, endoscopic tumor circumferential rate <50%, low pre-CRT T & N stage, low post-CRT T & N stage, small pretreatment tumor area, and large difference in tumor area before and after neoadjuvant CRT were predictive factors of pCR. A multivariate analysis found that only the difference in tumor area before and after neoadjuvant CRT was an independent predictor of pCR (P < 0.001). CONCLUSION: The difference in tumor area, as determined using radiologic tools, before and after neoadjuvant CRT may be important predictor of pCR. This clinical factor may help surgeons to determine which patients who received neoadjuvant CRT for locally advanced rectal cancer should undergo surgery.