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Background/aim Previous reports have indicated that increased expression of Jagged-1 (JAG1) may predict chemotherapy response and poor prognosis for patients with recurrent or metastatic colorectal cancer (CRC). This study aimed to investigate the clinical impact of JAG1 expression level in patients with CRC, including recurrence, especially in those diagnosed with lymph node-positive stage III CRC who underwent complete resection and appropriate adjuvant chemotherapy. Patients and methods All patients were enrolled through a retrospective chart review, and only those for whom the clinical course and all clinical information were adequately determined according to the inclusion criteria were selected for retrospective review through medical records. Immunohistochemical staining of JAG1 was performed using paraffin-embedded tissue. JAG1 expression was determined by scoring for staining intensity and percentage of positively stained cells; the final JAG1 score was determined as the sum of both scores. Results Sixteen patients who experienced relapse and 15 without (for over 3 years) were selected. The protein expression level of JAG1 showed a tendency for being lower in the group without recurrence, although not statistically significantly (p=0.083); however, the mean JAG1 expression score was significantly lower in the group without recurrence (1.53 vs. 3.19; p=0.004). The patients were divided into two groups with low and high JAG1 expression. The results showed that high JAG1 expression was significantly associated with recurrence of stage III CRC (p=0.029). Conclusion The expression of JAG1 may be a potential novel biomarker for predicting CRC recurrence.

Background/aim We investigated the clinical role of the molecular targets, APEX1 and Jagged-1, and the Apex1 - Jagged-1 cascade in gastric cancer cells. Materials and methods We used 6 human gastric cancer cell lines (SNU-1, SNU-5, SNU-16, NCI-N87, KATO- III and AGS), and demonstrated the chemosensitivity of APEX1 and Jagged-1 through the MTT assay and immunoblotting. Tumor growth was assayed following cisplatin and 5-FU treatment using a xenograft model injected with KATO-III cells. Moreover, gastric tumor samples from 9 patients, divided in 2 groups according to chemotherapy response, were examined by immunocytochemical (IHC) staining, and protein expression levels were scored. Results Following APEX1 knockdown, the MTT assay revealed that the IC50 of cisplatin and 5-FU in AGS cells was decreased approximately 7% and 15%, respectively, however, their decrease in chemoresistant KATO-III cells was decreased by approximately 21% and 67% for cisplatin and 5-FU, respectively. The tumor volume of KATO-III/sicontrol mice treated with cisplatin and 5-FU was affected less, compared with KATO-III/siAPEX1 mice treated with cisplatin and 5-FU. Also, the expression levels of APEX1, Jagged-1 and CD133, assayed by IHC staining, were higher in the chemorefractory group than in the chemoresponsive group. Conclusion Jagged-1-activated signaling by APEX1 plays a role in advanced gastric cancer.

Background/aim Colorectal cancer (CRC) is one of the most common in the world and its prevalence is rapidly increasing. Jagged-1-activated Notch signaling by apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) promotes CRC, and high expression of Jagged-1 is associated with poor prognosis. However, its clinical implication is unknown. The aim of this study was to investigate the clinical role of Jagged-1-activated Notch signaling by APEX1. Materials and methods The 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the anti-cancer efficacy of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan. Tissue from CRC patients was analyzed to assess the clinical specificity of Jagged-1 activated by APEX1. Results The half-maximal inhibitory concentration (IC50) in cells co-expressing APEX1 and Jagged-1 cells was higher than that in cells expressing only APEX1. These results indicated that the simultaneous expression of APEX1 and Jagged-1 might be associated with chemoresistance toward 5-FU, oxaliplatin, and irinotecan. Analysis of tissue from CRC patients revealed that high expression of Jagged-1 was associated with a statistically significantly low response to chemotherapy. Conclusion Overexpression of Jagged-1 by APEX1 might serve as a predictor of response to chemotherapy and of poor prognosis, and moreover may be a therapeutic target for chemotherapy of advanced CRC.