Loss of Beclin1 Expression and Nrf2 Overexpression are Associated with Poor Survival of Patients with Non-Small Cell Lung Cancer

2019 ◽  
Vol 18 (12) ◽  
pp. 1680-1687 ◽  
Author(s):  
Shuo Yu ◽  
Chuantao Cheng ◽  
Jia Wang ◽  
Jing Wang ◽  
Zhan Qu ◽  
...  

Background: Nrf2 pathway and autophagy are abnormally activated in response to cellular stress in various types of human cancers. In this study, we selected Beclin1 as an enter point to discuss the relationship between Nrf2 pathway and autophagy, and defined their associations with clinic pathological features and survival of the patients. Method: NSCLC specimens were processed for immunohistochemical and qRT-PCR to analyses the expression of Beclin1 and Nrf2. Kaplan-Meier method and log-rank test were used in the survival data. Results: Beclin1 protein level was found to be significantly associated with more advanced TNM stage (P = 0.035), lymph node metastasis (P = 0.017) and distant metastasis (P = 0.005). The expression of Nrf2 protein was associated with larger tumor size (P = 0.032), more advanced TNM stage (P = 0.011), lymph node metastasis (P = 0.045) and distant metastasis (P = 0.013). Beside there was a strong inverse relationship between Beclin1 and Nrf2 expression in the NSCLC tissues. Distant metastasis, Beclin1, Nrf2, and Beclin1-/Nrf2+ expression was conformed to be independent prognostic factors of patients. Conclusion: Both Nrf2 overexpression and Beclin1 lower-expression are independent indicators of a poor prognosis in NSCLC patients.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Cao ◽  
Lei Jiang ◽  
Liang-Yi Zhou ◽  
Yan-Ling Chen

Abstract Background Gallbladder carcinoma (GBC) was the most common malignancy of biliary tract. Patients with malignancies frequently present with activated coagulation pathways, which might potentially related to tumor progression and prognosis. The purpose of the study was to investigate the clinical significance of preoperative serum fibrinogen levels and platelet counts in GBC patients. Methods The preoperative fasting serum fibrinogen levels and platelet counts of 58 patients with GBC were measured by AUV2700 automatic biochemical analyzer, as well as 60 patients with cholesterol polyps and 60 healthy volunteers. Kaplan–Meier survival analysis was applied to show the correction between fibrinogen levels and outcome after surgery. Results The fibrinogen levels of patients with GBC were significantly higher than healthy gallbladder and cholesterol polyp of gallbladder (p < 0.001 and p < 0.001, respectively). In GBC, fibrinogen levels were associated with tumor depth (p = 0.001), lymph node metastasis (p = 0.002), distant metastasis (p < 0.001) and Tumor Node Metastasis (TNM) stage (p < 0.001). The levels in TNM stage IV disease were significantly higher than stage III or stage I + II disease (p = 0.048 and p < 0.001, respectively), and in TNM stage III disease were significantly higher than stage I + II disease (p = 0.002). Furthermore, the overall survival was better in low fibrinogen level group than in high fibrinogen level group (p < 0.001). However, thrombocytosis was not significantly associated with overall survivals (p > 0.05) in multivariate analysis. Conclusions The preoperative serum fibrinogen levels and platelet counts might be reliable biomarkers for the occurance of disease, tumor depth, lymph node metastasis, distant metastasis and advanced TNM stage in patients with GBC. The serum fibrinogen levels might be a prognostic factor to predict outcome for GBC patients suffering from surgery treatment. Anticoagulation therapy might be considered to control cancer progression in future studies.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shan Liang ◽  
Zhulin Yang ◽  
Daiqiang Li ◽  
Xiongying Miao ◽  
Leping Yang ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, but the genetic basis of PDAC is still unclear. In this study, Nectin-2 and DDX3 expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues were measured by immunohistochemical methods. Results showed that the percentage of positive Nectin-2 and DDX3 expression was significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P<0.01). The percentage of cases with positive Nectin-2 and DDX3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease (P<0.05orP<0.01). Positive DDX3 expression is associated with poor differentiation of PDAC. Kaplan-Meier survival analysis showed that positive Nectin-2 and DDX3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive Nectin-2 and DDX3 expression were independent poor prognosis factors in PDAC patients. In conclusion, positive Nectin-2 and DDX3 expression are associated with the progression and poor prognosis in PDAC patients.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Louqian Zhang ◽  
Weifei Fan ◽  
Li Xu ◽  
Qixing Mao ◽  
Yan Chen ◽  
...  

Rab27b is reported to associate with the development and progression of several types of human cancers. However, the relationship between Rab27b expression and the clinical characteristics of lung adenocarcinoma (LUAD) is rarely explored. In this present study, the TCGA database was consulted, followed by one-step quantitative reverse transcription polymerase chain reaction (qPCR), Western blot, and immunohistochemistry (IHC) analyses in LUAD cell lines and tissue samples. Rab27b expression levels were statistically higher in LUAD cell lines and tissue samples compared with a noncancerous cell line and tissue samples (p<0.05). Rab27b expression was statistically correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.019). Survival analysis and Kaplan-Meier curve revealed that Rab27b expression (p=0.006) and TNM stage (p=0.027) were independently associated with the unfavorable overall survival of patients with LUAD. These results indicate that high expression of Rab27b correlates with malignant attributes of LUAD and Rab27b may be identified as a potential indicator of metastasis and prognosis for LUAD.


2021 ◽  
Author(s):  
Jian Luo ◽  
Yuanzhi Zhu ◽  
Ying Long ◽  
Fei Huang ◽  
Xiaozou Luo ◽  
...  

Abstract Background Many cancer researchers have investigated the prognostic significance of LASP1 for survival of patients with various types of cancer. Nevertheless, the role LASP1 palyed in cancer prognosis remains unknown. In consequence, we carried out this study in order to comprehensively analyze the prognostic value of LASP1 in cancer patients. Methods A systematical research was conducted in electronic databases, such as PubMed, Embase and Web of Science. Eighteen studies meeting the inclusion criteria were enrolled. Overall survival (OS), recurrence-free survival (RFS) and various clinicopathological parameters were used as the endpoints in this study. Results A total of 2023 cancer patients from eighteen studies were finally enrolled into our meta-analysis. The results revealed that the cancer patients with high expression of LASP1 exhibited shorter OS (HR = 2.04, 95%CI = 1.77–2.34, P < 0.01) and RFS (HR = 2.11, 95%CI = 1.51–2.95, P < 0.01) than those with low expression of LASP1, and patients whose tumors expressed high LASP1 had shorter OS in lung cancer (HR = 2.20, 95%CI = 1.45–3.36, P < 0.01) and gastric cancer (HR = 1.64, 95%CI = 1.14–2.36, P < 0.01) respectively. Furthermore, the cancer patients whose tumors expressed high LASP1 were apparently associated with advanced TNM stage (OR = 2.92, 2.27–3.76, P < 0.01), earlier lymph node metastasis (OR = 2.69, 1.62–4.45, P < 0.01), advanced T classification (OR = 2.17, 1.48–3.18, P < 0.01) and earlier distant metastasis (OR = 2.56, 1.03–6.35, P = 0.04) when compared to those whose tumors expressed low LASP1. Conclusions Our study showed that the high LASP1 expression might be an undesirable predictor for patients with various types of cancers in the aspect of OS, RFS, TNM stage, lymph node metastasis, T classification and distant metastasis, and the high LASP1 expression might be an undesirable predictor for lung cancer patients and gastric cancer patients. Therefore, the expression of LASP1 might be utilized as a novel indicator in judging the prognosis of cancer patients, especially in lung cancer and gastric cancer.


2021 ◽  
Author(s):  
Peng Cao ◽  
Lei Jiang ◽  
Liang-Yi Zhou ◽  
Yan-ling Chen

Abstract Background: Gallbladder carcinoma (GBC) was the most common malignancy of biliary tract. Patients with malignancies frequently present with activated coagulation pathways, which mightpotentially related to tumor progression and prognosis. The purpose of the study was to investigate the clinical significance of preoperative serum fibrinogen levels and platelet counts in GBC patients.Methods: The preoperative fasting serum fibrinogen levels and platelet counts of 58 patients with GBC were measured by AUV2700 automatic biochemical analyzer, as well as 60 patients with cholesterol polyps and 60 healthy volunteers. Kaplan–Meier survival analysis was applied to show the correction between fibrinogen levels and outcome after surgery.Results: The fibrinogen levels of patients with GBC were significantly higher than healthy gallbladder and cholesterol polyp of gallbladder (p<0.001 and p<0.001,respectively). In GBC, fibrinogen levels were associated with tumor depth (p=0.001), lymph node metastasis (p=0.002), distant metastasis (p<0.001) and Tumor Node Metastasis (TNM) stage (p<0.001).The levels in TNM stage Ⅳ disease were significantly higher than stage Ⅲ or stage Ⅰ+Ⅱ disease(p=0.048 and p<0.001, respectively), and in TNM stage Ⅲ disease were significantly higher than stageⅠ+Ⅱ disease(p=0.002).Furthermore, the overall survival was better in low fibrinogen level group than in high fibrinogen level group (p<0.001).However, thrombocytosis was not significantly associated with overall survivals(p>0.05) in univariate analysis.Conclusion: The preoperative serum fibrinogen levels and platelet counts might be reliable biomarkers for the occurance of disease, tumor depth, lymph node metastasis, distant metastasis and advanced TNM stage in patients with GBC. The serum fibrinogen levels might be a prognostic factor to predict outcome for GBC patients suffering from surgery treatment. Anticoagulation therapy might be considered to control cancer progression in future studies.


2021 ◽  
Vol 11 ◽  
Author(s):  
Lingxiao Qiu ◽  
Pan Song ◽  
Pingmei Chen ◽  
Huaqi Wang ◽  
Fangfang Li ◽  
...  

BackgroundPrimary pulmonary mucoepidermoid carcinoma (PMEC) is an extremely rare malignancy. Its clinical characteristics and prognosis are not fully understood. This study evaluated clinical characteristics and prognostic factors of PMEC and established a nomogram to predict its 1-, 3-, 5- and 10-year cancer-specific survival (CSS) rates.MethodsIn the Surveillance, Epidemiology, and End Results database from January 1, 2016 to December 31, 2016, patients pathologically diagnosed with PMEC were identified. Kaplan–Meier analysis and Cox regression were performed to evaluate the CSS stratified by different covariates. A predictive nomogram model was built and validated by the concordance index (C-index) and calibration curves.ResultsA total of 585 PMEC patients were identified. A total of 408 (70%) of patients were placed into the training cohort, and 177 (30%) patients were placed into the validation cohort. The 5- and 10-year CSS rates of stage I–II PMEC patients were 91.4 and 88.9, respectively. The 1-, 3- and 5-year CSS rates of stage III–IV PMEC were 56.5, 39.45, and 32.1%, respectively. Survival curves showed that older age, large tumor size, poor differentiation, and high TNM stage were associated with a significantly worse prognosis. CSS outcomes were significantly better in patients who received surgical treatments (surgical alone, surgery plus radiation and/or chemotherapy). Patients who received radiation and/or chemotherapy had the worst prognosis. Multivariate Cox results revealed that covariates, including age, tumor laterality, tumor sizes, pathological differentiation, lymph node metastasis, distant metastasis, TNM stage and therapy, were independent prognostic factors for PMEC. These factors were used to construct a nomogram. The C-index of the nomogram was 0.921. The calibration curve presented favorable consistency between the predicted CSS and actual observations. This nomogram was validated by the validation cohort. The C-index of the validation cohort was 0.968.ConclusionAge, bilateral tumors, tumor size, pathological differentiation grade, lymph node metastasis, distant metastasis, TNM stage and therapy were independent prognostic factors of PMEC patients. The first nomogram for predicting the CSS of PMEC was built and validated, showing its potential value in practice.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yuejuan Xu ◽  
Jue Sun ◽  
Jianhua Xu ◽  
Qi Li ◽  
Yuewu Guo ◽  
...  

Background. Gastric cancer (GC) is an important malignant disease around the world. Abnormalities of microRNAs (miRNAs) have been implicated in carcinogenesis of various cancers. In the present study, we examined miR-21 expression in human gastric cancer with lymph node metastasis and attempted to uncover its relationship with clinicopathologic data, especially with lymph node metastasis.Materials and Methods. The expression levels of miR-21 in the tumor specimens of GC patients were quantified by RT-PCR. The correlation between miR-21 level and multiple clinicopathological factors was then examined by Mann-Whitney test, Kaplan-Meier survival analysis, and operating characteristic (ROC) analysis.Results. The expression level of miR-21 was higher in GC patients with lymph node metastasis than in those without lymph node metastasis (P<0.05). Expression level of miR-21 was significantly correlated with histologic type, T stage, lymph node metastasis and pTNM stage. The overall survival rates in GC patients with low upregulated miR-21 expression were significantly higher than those with high upregulated miR-21 (P<0.05).Conclusion. A close association is implicated between the elevated miR-21and lymph node metastasis, which could potentially be exploited as a practical biomarker for lymph node metastasis in patients with GC.


2021 ◽  
pp. 1-7
Author(s):  
Lili Huang ◽  
Yan Zhou ◽  
Qiuwei Sun ◽  
Lei Cao ◽  
Xueguang Zhang

BACKGROUND and OBJECTIVE: Gastric adenocarcinoma (GAC) is one of the most common malignancies. Increasing data have indicated a correlation between soluble B7-H3 (sB7-H3) levels and tumor malignancies. In this study, we aim to investigate the level of soluble B7-H3 in serum of GAC patients. Further, we analyze the correlation between sB7-H3 level and tissue B7-H3 expression and explore the clinical evaluation value of sB7-H3 associated with pathological characteristics and prognosis of GAC patients. METHODS: One hundred and twenty-eight serum and tissue samples of GAC 20 serum and tissue samples of gastritis patients and 77 serum, 5 tissue samples of healthy controls were collected. The serum levels of sB7-H3 were detected by Enzyme-linked immunosorbent assay (ELISA), while the expression of membrane B7-H3 (mB7-H3) and Ki67 were evaluated by immunohistochemistry. The correlation between sB7-H3 and mB7-H3, sB7-H3 and Ki67, sB7-H3 or mB7-H3 and clinical features were analyzed by Pearson’s Chi-square test. RESULTS: Both serum level of sB7-H3 and tissue B7-H3 of GAC patients were significantly higher than those of gastritis patients and healthy controls. sB7-H3 level was correlated with total B7-H3 expression in tissues (r= 0.2801, P= 0.0014). Notably, the concentration of sB7-H3 was correlated with its expression of membrane form in tumor cells (r= 0.3251, P= 0.002) while not in stromal cells (r= 0.07676, P= 0.3891). Moreover, the levels of sB7-H3 in patients with TNM stage III/IV or with Infiltration depth T3/T4 or with lymph node metastasis were significantly higher than those of patients with TNM stage I/II (P= 0.0020) or with Infiltration depth T1/T2 (P= 0.0169) or with no lymph node metastasis (P= 0.0086). Tumor B7-H3 score, but not stromal B7-H3 score, in patients with TNM stage III/IV or with lymph node metastasis was significantly higher than those with TNM stage I/II (P= 0.0150) or with no lymph node metastasis (P= 0.182). CONCLUSIONS: Soluble B7-H3 level may reflect the tissue B7-H3 expression on tumor cells of GAC tissues. Elevated level of sB7-H3 in serum suggests poor clinical pathological characteristics of GAC patients.


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