Significance of hypoxia inducible factor-1 expression in liver metastasis of colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 464-464
Author(s):  
Yuma Wada ◽  
Yuji Morine ◽  
Satoru Imura ◽  
Tetsuya Ikemoto ◽  
Shuichi Iwahashi ◽  
...  

464 Background: In colorectal liver metastasis (CRLM), the difference of tumor malignancy between primary and metastatic lesion has been elucidated. Hypoxia inducible factor-1 (HIF-1) represent tumor malignancy including angiogenesis, tumor growth and epithelial mesenchymal transition (EMT). The aim of this study was to investigate the difference of tumor malignancy between metastatic and primary lesion of CRLM and its impact for patient’s prognosis. Methods: In an initial curative hepatectomy of 75 cases in CRLM, HIF-1 expression in primary and metastatic lesion was evaluated by immunostaining method (Sigma-Aldrich, HPA 001275). Staining score was classified as follows, staining intensity (0: negative, 1: low, 2: medium, 3: high) and staining area (0: 0%, 1: -25%, 2: 26-50%, 3: ≥ 51%), and defined more than 4 points as positive expression. We evaluated the clinicopathological features according to HIF-1 expression. Results: Regarding HIF-1 expression of metastatic site, we divided into the positive group (n = 54) and the negative group (n = 21). There was no difference between metastatic HIF-1 expression and clinicopathological factors. Nevertheless, in overall survival, multivariate analysis revealed that HIF-1 positive in metastasis (HR: 2.850, p = 0.042) and poor differentiation type of primary lesion (HR: 20.873, p = 0.001) were independent prognostic factors. HIF-1 positive and negative patients were 3 year survival of 95.2% and 58.6%, respectively. Also, in disease free survival, HIF-1 positive in metastasis (HR: 2.608, p = 0.004), Synchronous (HR: 1.794, p = 0.049), Grade BC (HR: 2.145, p = 0.008), and lymph node metastasis in primary lesion (HR: 2.070, p = 0.016) was identified. Regarding HIF-1 expression of primary site, we divided into 51 cases of positive group and 24 cases of negative group. There was no relationship to clinicopathological factors as well as HIF-1 expression in metastasis, besides HIF-1 expression of prognosis was not associated. Conclusions: In CRLM, HIF-1 expression in the metastatic lesion is not associated with the primary lesion and may be useful as prognostic marker.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 75-75
Author(s):  
Hideya Kashihara ◽  
Mitsuo Shimada ◽  
Kozo Yoshikawa ◽  
Jun Higashijima ◽  
Takuya Tokunaga ◽  
...  

75 Background: Indoleamine 2,3-dioxygenase (IDO) downregulates T cell activation and is related to immune tolerance. The aim of this study was to clarify the significance of IDO expression and to analyze the relationships among the expression of IDO, TGF-b, and Foxp3 in gastric cancer (GC). Methods: Sixty patients who underwent curative gastrectomy for stage III gastric cancer were included in this study. The expressions of IDO, TGF-b, and Foxp3 were examined by immunohistochemistry. The patients were divided into two groups: the IDO-positive group (n = 23) and negative group (n = 37). Clinicopathological factors were compared between the two groups. Univariate analysis was used to assess overall (OS) and disease-free survival (DFS) in several prognostic factors. Multivariate analysis was used to identify the independent prognostic factors. Results: IDO expression was not positively correlated with any clinicopathological factors. IDO expression was positively correlated with TGF-b expression (p < 0.05) and TGF-b expression was positively correlated with FoxP3 expression (p < 0.05). Overall survival (OS) rates were significantly poorer in the IDO-positive group compared with the IDO-negative group (3-year OS, 78.5% vs. 90%, respectively; p < 0.05). Multivariate analysis identified IDO expression as independent prognostic factors in OS. Disease-free survival (DFS) was significantly poorer in the IDO-positive group compared with the IDO-negative group (3-year DFS, 59.3% vs. 69.3%, respectively; p < 0.05). Conclusions: IDO is associated with poor prognosis and immuno-tolerance through Treg in Stage III GC.


2020 ◽  
Author(s):  
Yuki Hirose ◽  
Jun Sakata ◽  
Takashi Kobayashi ◽  
Kohei Miura ◽  
Kizuki Yuza ◽  
...  

Abstract Background: NAD(P)H: quinone oxidoreductase-1 (NQO1) is an antioxidant and detoxifying protein, which contributes to chemoresistance in some types of cancer. This study aimed to evaluate how NQO1 affects the response to preoperative chemotherapy and survival after hepatectomy for patients with colorectal liver metastasis (CRLM).Methods: A retrospective analysis was conducted of 88 consecutive patients who underwent curative-intent hepatectomy for CRLM, with a median follow-up period of 65.4 months. Of the 88 patients, preoperative chemotherapy was administered to 30 patients, among which the association between NQO1 status and response to preoperative chemotherapy was evaluated. Immunohistochemistry of the resected specimens was conducted using monoclonal anti-NQO1 antibody.Results: According to NQO1 expression in tumor cells of CRLM, the 88 patients were classified into those with NQO1 expression (the NQO1-positive group) (n = 61) and those with loss of NQO1 expression (the NQO1-negative group) (n = 27). According to NQO1 expression in non-neoplastic epithelial cells of the large intrahepatic bile ducts, which typically show NQO1-positive expression, the 88 patients were classified into the NQO1 non-polymorphism group (positive expression, n = 69) and the NQO1 polymorphism group (loss of expression, n = 19). The NQO1-positive group had significantly worse overall survival than the NQO1-negative group (cumulative 5-year overall survival rate: 66.5% vs. 90.9%, p = 0.026), whereas NQO1 polymorphism status was not associated with overall survival. NQO1-positive expression was an independent adverse prognostic factor in multivariate analysis (hazard ratio: 5.296, p = 0.007). The presence of NQO1 polymorphism (loss of NQO1 expression in non-neoplastic epithelial cells of the large intrahepatic bile ducts) was significantly associated with a better response to preoperative chemotherapy for CRLM (p = 0.004).Conclusions: NQO1-positive expression may be an adverse prognostic factor after hepatectomy for CRLM. NQO1 polymorphism status may be a clinically useful biomarker for predicting the radiological response to preoperative chemotherapy for CRLM.


2021 ◽  
Author(s):  
Ying Li ◽  
Zhaobing Ni ◽  
Renjie He ◽  
Junyu Zhang ◽  
Zhimou Zhang ◽  
...  

AbstractAnalyzing the influence of emotion on false memory through electroencephalogram is helpful to further explore the cognition function of brain. In this study, we improved the Deese-Roediger-McDermott paradigm experiment to study the false memory. The memory materials are combined with mixed emotions, which are closer to real life. Twenty-eight participants were randomly divided into positive group and negative group. We used music to induce the participants in the positive group and the negative group to generate corresponding emotions. Finally, we analyzed the difference between the positive group and the negative group from the behavior data, source location and cortex functional network of event related potential. The results of behavioral data analysis show that the false memory rate of positive group (85%) is significantly higher than that of negative group (72%). The results of source localization show that the brain of the positive group is more active than that of the negative group, and the difference of brain activation location between the two groups is mainly manifested in the BA24 and BA45 brain regions. The results of cortex functional network show that the node degree, clustering coefficient, global efficiency and small-world property of the positive group are significantly higher than those of the negative group. It can be found from the three aspects that participants’ emotional state and brain’s understanding of semantic are the main reasons for the difference in the incidence of false memory between the two groups.


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