scholarly journals Association of γ-aminobutyric acid type A receptor-associated protein with prognosis in patients after radical pancreatic cancer treatment

2020 ◽  
Author(s):  
Chao Zhang ◽  
Wenhao Tang ◽  
Yanyuan Tu ◽  
Zurong Yuan ◽  
Wei Wang ◽  
...  

Abstract Background:Pancreatic cancer is difficult to cure and many factors influence patient prognosis, of which autophagy is a recent research hotspot, and GABARAP plays a key role in autophagy, which has been found to interfere with cancer cell survival and metastasis in a variety of tumours. In this study, we analysed the correlation between GABARAP and patient prognosis in pancreatic cancer, as well as its correlation with clinicopathological parameters and its impact on the efficacy of chemotherapy in pancreatic cancer patients.Methods: The pancreatic tissues of 76 pancreatic cancer patients after R0 resection were screened according to the criteria, and the expression levels of GABARAP were determined by using immunohistochemistry (MaxVision) to label the pancreatic cancer tissues and normal pancreatic tissue around carcinoma in these two types of specimens, and the relationship between GABARAP and other factors and the disease-free and overall survival of patients after radical pancreatic cancer treatment was evaluated by single factor survival analysis and Cox regression analysis.Results:The expression ratio of GABARAP in pancreatic cancer tissue was drastically higher than that in normal pancreatic tissue adjacent to cancer. Cox regression model evaluation showed that GABARAP and postoperative adjuvant chemotherapy were the overall survival of patients after radical pancreatic cancer Period independent prognostic indicators and both are protective factors for the prognosis of pancreatic cancer patients. Further data analysis found that postoperative chemotherapy drastically increased the total patient Survival period in GABARAP-negative patients but had no drastically effect on the patient's relapse-free survival period.Conclusion: The expression of GABARAP in pancreatic cancer tissues was drastically up-regulated, and patients with high expression of GABARAP in pancreatic cancer tissues had better prognosis, but had no drastically effect on the relapse-free survival of patients after radical operation of pancreatic cancer. The expression of GABARAP in pancreatic cancer tissues and Postoperative adjuvant chemotherapy is an independent indicator of patients' prognosis after radical pancreatic cancer resection. Both are protective factors. The high expression of GABARAP in pancreatic cancer may indicate that the adjuvant chemotherapy is low benefit.

2020 ◽  
Author(s):  
Chao Zhang ◽  
Wenhao Tang ◽  
Yanyuan Tu ◽  
Zurong Yuan ◽  
Wei Wang ◽  
...  

Abstract Purpose: To discuss the value and possible causes of γ-aminobutyric acid type A receptor-associated protein (GABARAP) expression and multiple clinicopathological factors in the prognosis of patients after radical pancreatic cancer treatment.Methods: The pancreatic tissues of 76 pancreatic cancer patients after R0 resection were screened according to the criteria, and the expression levels of GABARAP were determined by using immunohistochemistry (MaxVision) to label the pancreatic cancer tissues and normal pancreatic tissues at the peri-cancer level in these two types of specimens, and the relationship between GABARAP and other factors and the disease-free and overall survival of patients after radical pancreatic cancer treatment was evaluated by single factor survival analysis and Cox regression analysis.Results:The expression ratio of GABARAP in pancreatic cancer tissue was 55.26% (42/76), which was drastically higher than that in normal pancreatic tissue adjacent to cancer (21.42% (12/76). In 76 patients, the middle relapse-free survival time after radical operation for pancreatic cancer was 12.8 months, and the middle overall survival time was 17.8 months. Forty-one patients found relapse on CT, and the recurrence site: local recurrence accounted for 17.1% (7/41) Distant metastasis accounted for 78.0% (32/41), and local recurrence with distant metastasis accounted for 4.9% (2/41). Among the three recurrence methods, there was no drastical difference in survival time from relapse to death (P> 0.05). Cox regression model evaluation showed that GABARAP (P = 0.044) and postoperative adjuvant chemotherapy (P = 0.038) were the overall survival of patients after radical pancreatic cancer Period independent prognostic indicators and both are protective factors for the prognosis of pancreatic cancer patients. Further data analysis found that postoperative chemotherapy had no drastical effect on the relapse-free survival and overall survival of 42 GABARAP-positive patients with cancer tissue, while in 34 GABARAP-negative patients, postoperative chemotherapy drastically increased the total patient Survival period (P = 0.041) but had no drastical effect on the patient's relapse-free survival periodConclusion: The expression of GABARAP in pancreatic cancer tissues was drastically up-regulated, and patients with high expression of GABARAP in pancreatic cancer tissues had better prognosis, but had no drastical effect on the relapse-free survival of patients after radical operation of pancreatic cancer. The expression of GABARAP in pancreatic cancer tissues and Postoperative adjuvant chemotherapy is an independent indicator of patients' prognosis after radical pancreatic cancer resection. Both are protective factors. The high expression of GABARAP in pancreatic cancer may indicate that the adjuvant chemotherapy is low benefit.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 475-475
Author(s):  
Ryo Kanata ◽  
Masato Ozaka ◽  
Seita Kataoka ◽  
Kazunaga Ishigaki ◽  
Ikuhiro Yamada ◽  
...  

475 Background: In Japan, adjuvant chemotherapy with S-1 for 6 months is standard care for resected pancreatic cancer. However, the efficacy of chemotherapy for recurrent pancreatic cancer(RPC) after adjuvant S-1 chemotherapy is not well evaluated. Methods: Medical records were retrospectively reviewed for consecutive patients who had RPC after adjuvant S-1 treatment and received chemotherapy between April 2013 and July 2016. Recurrence free interval (RFI) was defined as the interval from adjuvant S-1 initiation to cancer recurrence. Overall survival (OS) and progression free survival (PFS) after 1st line chemotherapy for RPC were compared between patients with RFIs of shorter than 6 month (Group S) and longer than 6 months (Group L). Results: In the 53 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 5.1 months, and the median RFI was 8.3 months. After recurrence, they received Gemcitabine alone (20 patients), Gemcitabine+nab-paclitaxel (28 patients), modified FOLFIRINOX (one patient), and other regimen (4 patients). In all patients, the median PFS was 7.3 months and the median OS was 14.8 months. When compered in two groups (group S and group L), median OS in group S and group L was 6.7 months (95% confidence interval(CI): 4.2-12.9) and NA (95% CI: 13 months-NA) , respectively (p < 0.001), and median PFS was 3.8 months (95%CI: 2.5-9.1) and 7.3 months (95%CI: 3.9-15.3), respectively (p = 0.11). Multivariate Cox regression analysis revealed CEA < 4.0 mg/dl before chemotherapy and an RFI of ≥ 6 months were significantly associated with longer survival. Conclusions: These data suggest that RFI < 6 months is a surrogate marker for a poor prognosis in patients with RPC.


2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Fahong Wu ◽  
Yanling Chen ◽  
Jinhai Zhu

Abstract Pancreatic cancer (PaCa) is a common malignant tumor of the digestive system with poor prognosis and no ideal treatment for inoperable patients, which is partly due to delayed diagnoses. It is recently reported that the protein histidine phosphatase LHPP is a tumor suppressor in hepatocellular carcinoma, cervical cancer, and bladder cancer. So far, there is no study on the expression level of LHPP in PaCa, and its mechanism of action on tumors is unclear. In this experiment, LHPP expression was lower in cancer tissues than that in normal pancreatic tissue, and clinicopathological results showed that LHPP expression was correlated with the degree of differentiation and lymphatic metastasis of pancreatic carcinoma. The biological characteristics of LHPP in PaCa cells were examined by the cell counting kit-8 assay, transwell assay, and monoclonal formation test. The inhibitory mechanism of LHPP in PaCa cells was determined using Western blotting and flow cytometry. The results showed that LHPP restrained PaCa cell proliferation, migration, and invasion. Increased LHPP expression promoted the apoptosis of PaCa cells through higher activation of cleaved-PARP and cleaved-Casp3 and lower activation of cIAP1. Importantly, the increase in LHPP enhanced PTEN expression and decreased the phosphorylated AKT level. Moreover, LHPP-induced apoptosis was diminished by SC79 (AKT activator) in PaCa cells. In conclusion, LHPP blocks proliferation, migration, and invasion and enhances apoptosis in PaCa cells through the PTEN/AKT signaling pathway.


2010 ◽  
Vol 5 (4) ◽  
pp. 435-438
Author(s):  
Agnieszka Dettlaff-Pokora ◽  
Justyna Kostro

AbstractSignal transducer and activator of transcription 3 (STAT3) has four isoforms: α, β, γ and δ. STAT3α and STAT3β are the transcriptionally active isoforms, while STAT3γ and STAT3δ are the products of STAT3 proteolytic degradation. STAT3 plays an important role in angiogenesis, cell proliferation and apoptosis. High levels of STAT3β in blood cells from acute leukaemia patients have been reported, suggesting that STAT3β may play an important role in cancerogenesis. Fourteen pancreatic cancer patients and six chronic pancreatitis patients were included in this pilot study. Levels of STAT3 isoforms from samples with pancreatic cancer and in adjacent histologically-normal pancreatic tissue were analysed. Pancreas from chronic pancreatitis patients served as a non-neoplastic tissue. Western-blot analysis of STAT3 proteins with the use of anti-STAT3 antibodies was performed. STAT3α and STAT3β isoforms in both cancerous and in adjacent normal tissues were found in 10 of 14. In chronic pancreatitis patients, only STAT3α and STAT3δ were detected. STAT3β was absent in pancreas from chronic pancreatitis patients, in contrast to pancreatic cancer patients. The presence of STAT3β in pancreatic cancer and in adjacent histologically-normal tissues, but not in inflamed tissues suggests that STAT3β may play a key role in cancer development.


2021 ◽  
pp. postgradmedj-2021-139981
Author(s):  
Shimin Tang ◽  
Hao Jiang ◽  
Zhijun Cao ◽  
Qiang Zhou

IntroductionProstate cancer is a common malignancy in men that is difficult to treat and carries a high risk of death. miR-219-5p is expressed in reduced amounts in many malignancies. However, the prognostic value of miR-219-5p for patients with prostate cancer remains unclear.MethodsWe retrospectively analysed data from 213 prostate cancer patients from 10 June 2012 to 9 May 2015. Overall survival was assessed by Kaplan-Meier analysis and Cox regression models. Besides, a prediction model was constructed, and calibration curves evaluated the model’s accuracy.ResultsOf the 213 patients, a total of 72 (33.8%) died and the median survival time was 60.0 months. We found by multifactorial analysis that miR-219-5p deficiency increased the risk of death by nearly fourfold (HR: 3.86, 95% CI): 2.01 to 7.44, p<0.001) and the risk of progression by twofold (HR: 2.79, 95% CI: 1.68 to 4.64, p<0.001). To quantify each covariate’s weight on prognosis, we screened variables by cox model to construct a predictive model. The Nomogram showed excellent accuracy in estimating death’s risk, with a corrected C-index of 0.778.ConclusionsmiR-219-5p can be used as a biomarker to predict death risk in prostate cancer patients. The mortality risk prediction model constructed based on miR-219-5p has good consistency and validity in assessing patient prognosis.


2019 ◽  
Vol 49 (8) ◽  
pp. 714-718
Author(s):  
Hao Yu ◽  
Linlin Zhang ◽  
Dapeng Li ◽  
Naifu Liu ◽  
Yueju Yin ◽  
...  

Abstract Objectives The current study was aimed to evaluate the efficacy and toxicity of postoperative adjuvant chemotherapy (CT) combined with intracavitary brachytherapy (ICRT) in cervical cancer patients with intermediate-risk. Methods We analyzed the medical records of 558 patients who were submitted to radical surgery for Stage IB-IIA cervical cancer. A total of 172 of those 558 patients were considered intermediate-risk according to the GOG criteria. Among those 172 patients, 102 were subjected to CT combined with ICRT (CT+ICRT) and the remaining 70 patients were treated with concurrent chemoradiation (CCRT). The 3-year disease free survival (DFS), overall survival (OS), and complications of each group were evaluated and analyzed. Results No significant difference was observed in 3-year DFS or OS of the patients submitted to CT+ICRT and CCRT. Importantly, the frequencies of grade III to IV acute complications were significantly higher in patients submitted to CCRT than in those treated with CT+ICRT (Hematologic, P = 0.016; Gastrointestinal, P = 0.041; Genitourinary, P = 0.019). Moreover, the frequencies of grade III–IV late complications in patients treated with CCRT were significantly higher compared with CT+ICRT-treated patients (Gastrointestinal, P = 0.026; Genitourinary, P = 0.026; Lower extremity edema, P = 0.008). Conclusions Postoperative adjuvant CT+ICRT treatment achieved equivalent 3-year DFS and OS but low complication rate compared to CCRT treatment in early stage cervical cancer patients with intermediate-risk.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yong-Qu Zhang ◽  
Fan Zhang ◽  
Yun-Zhu Zeng ◽  
Min Chen ◽  
Wen-He Huang ◽  
...  

PurposeThe basic helix-loop-helix transcription factor (bHLH) transcription factor Twist1 plays a key role in embryonic development and tumorigenesis. p53 is a frequently mutated tumor suppressor in cancer. Both proteins play a key and significant role in breast cancer tumorigenesis. However, the regulatory mechanism and clinical significance of their co-expression in this disease remain unclear. The purpose of this study was to analyze the expression patterns of p53 and Twist1 and determine their association with patient prognosis in breast cancer. We also investigated whether their co-expression could be a potential marker for predicting patient prognosis in this disease.MethodsTwist1 and mutant p53 expression in 408 breast cancer patient samples were evaluated by immunohistochemistry. Kaplan-Meier Plotter was used to analyze the correlation between co-expression of Twist1 and wild-type or mutant p53 and prognosis for recurrence-free survival (RFS) and overall survival (OS). Univariate analysis, multivariate analysis, and nomograms were used to explore the independent prognostic factors in disease-free survival (DFS) and OS in this cohort.ResultsOf the 408 patients enrolled, 237 (58%) had high mutant p53 expression. Two-hundred twenty patients (53.9%) stained positive for Twist1, and 188 cases were Twist1-negative. Furthermore, patients that co-expressed Twist1 and mutant p53 (T+P+) had significantly advanced-stage breast cancer [stage III, 61/89 T+P+ (68.5%) vs. 28/89 T-P- (31.5%); stage II, 63/104 T+P+ (60.6%)vs. 41/104 T-P- (39.4%)]. Co-expression was negatively related to early clinical stage (i.e., stages 0 and I; P = 0.039). T+P+ breast cancer patients also had worse DFS (95% CI = 1.217–7.499, P = 0.017) and OS (95% CI = 1.009–9.272, P = 0.048). Elevated Twist1 and mutant p53 expression predicted shorter RFS in basal-like patients. Univariate and multivariate analysis identified three variables (i.e., lymph node involvement, larger tumor, and T+P+) as independent prognostic factors for DFS. Lymph node involvement and T+P+ were also independent factors for OS in this cohort. The total risk scores and nomograms were reliable for predicting DFS and OS in breast cancer patients.ConclusionsOur results revealed that co-expression of mutant p53 and Twist1 was associated with advanced clinical stage, triple negative breast cancer (TNBC) subtype, distant metastasis, and shorter DFS and OS in breast cancer patients. Furthermore, lymph nodes status and co-expression of Twist1 and mutant p53 were classified as independent factors for DFS and OS in this cohort. Co-evaluation of mutant p53 and Twist1 might be an appropriate tool for predicting breast cancer patient outcome.


Author(s):  
Caihong Li ◽  
Honglan Zhu ◽  
Changlu Liu ◽  
Ya Liu ◽  
Ting Huang ◽  
...  

AbstractObjective: A number of recent clinical studies have identified a relationship between elevated expressions of 14-3-3 and poorer patient prognosis in the context of several cancers. The present meta-analysis was therefore conducted to gain an enhanced understanding of the prognostic importance of 14-3-3 levels in cancer patients. Methods: Two reviewers independently systematically reviewed the Web of Science, Embase, and PubMed databases to identify published, suitable studies through October 2019. The correlation between the level of 14-3-3 and cancer patient survival were assessed based upon pooled HR (hazard ratios) and 95% CI (confidence intervals) derived from chosen studies. Results: In total we were able to identify 22 eligible studies that had enrolled 2676 patients in the present meta-analysis. Assessment of these studies revealed that elevated 14-3-3 level correlated significantly with poorer OS (overall survival) (HR : 1.93, 95% CI : 1.42-2.61) in cancer patients. This was true even when studies were analyzed in subgroups according to tumor type, sample size, analysis type, and method of HR determination. With respect to disease-free survival (DFS), the pooled HR for cancer patients expressing high levels of 14-3-3 was 1.89 (95% CI: 1.56-2.30). Patients with elevated 14-3-3 expression also exhibited reduced CSS (cancer-specific survival) (HR: 3.47, 95% CI: 2.12-5.69).Conclusions: The outcomes indicate that higher level of 14-3-3 correlates with poorer patient prognosis in a range of cancer types.Keywords: Meta-analysis, Prognosis, 14-3-3 Proteins C Continuous...


Sign in / Sign up

Export Citation Format

Share Document