scholarly journals The Prognostic Role of SIRT1-Autophagy Axis in Gastric Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Guanglin Qiu ◽  
Xuqi Li ◽  
Chao Wei ◽  
Xiangming Che ◽  
Shicai He ◽  
...  

Aim. Sirtuin 1 (SIRT1) can induce autophagy through deacetylation of Beclin-1 and other autophagy mediators. However, the relationship between SIRT1 and autophagy in GC has not been defined. Therefore, the aim of this study was to confirm the prognostic value of SIRT1 and Beclin-1 and their relationship in GC patients. Methods. Transmission electron microscopy (TEM) was performed to examine the autophagy in GC patients. Immunohistochemistry was used to examine the expression of SIRT1, Beclin-1 in GC, and adjacent nonneoplastic mucosa. Results. In 7 out of 8 GC patients’ samples examined by TEM, more autophagic vesicles were observed in GC tissues compared to adjacent nonneoplastic mucosa tissue. A positive correlation between SIRT1 and Beclin-1 expression was observed. Furthermore, Beclin-1 or SIRT1 expression alone or their combined expression were significantly correlated with advanced clinicopathological parameters. High Beclin-1 and SIRT1 expression alone and their combined high expression predicted shorter overall survival and relapse-free survival. Both high Beclin-1 and SIRT1 expressions were independent prognostic factors for poor survival of GC. Conclusions. Based on our results we can conclude that SIRT1 and Beclin-1 expression alone or in combination can be used as prognostic indicator and may represent new therapeutic targets in GC.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yun-Qian Cui ◽  
Fei Meng ◽  
Wen-Li Zhan ◽  
Zhou-Tong Dai ◽  
Xinghua Liao

This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment.


2020 ◽  
pp. jclinpath-2020-206868
Author(s):  
Wei Sang ◽  
Jing Xue ◽  
Li-Ping Su ◽  
Abulajiang Gulinar ◽  
Qian Wang ◽  
...  

AimsA growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma.MethodsExpression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson’s X2 test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson’s or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis.ResultsHigh expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients.ConclusionOur research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.


2013 ◽  
Vol 34 (6) ◽  
pp. 379-386 ◽  
Author(s):  
Jing He ◽  
Fengmei Zhang ◽  
Ying Wu ◽  
Wei Zhang ◽  
Xiaoli Zhu ◽  
...  

BACKGROUND: Recent studies have shown that microRNAs (miRNA) have prognostic values in cancers. This meta-analysis seeks to summarize the global predicting role of miR-155 for survival in patients with a variety of carcinomas.METHODS: Eligible studies were identified through multiple search strategies. Data were extracted from studies investigating the relationship between miR-155 expression and survival in cancer patients. Combined hazard ratios (HRs) of miR-155 for outcome were analyzed.RESULTS: A total of 16 studies dealing with various carcinomas were included for this meta-analysis. For overall survival, higher miR-155 expression could significantly predict worse outcome with the pooled HR of 2.057 (95% CI: 1.392–3.039). For relapse or progress-free survival, elevated miR-155 was also a significant predictor, with a combined HR of 1.918 (95% CI: 1.311–2.806,). In addition, subgroup analysis showed that higher expression of miR-155 had the trends to predict worse outcome in lung cancer. However, the HRs did not reach the statistical significance.CONCLUSION: Our findings suggest that miR-155 detection has a prognostic value in cancer patients. Regularly measuring miR-155 expression may be useful in clinical practice.


2020 ◽  
Vol 6 (2) ◽  
pp. 34-38
Author(s):  
Mohammad Moniruzzaman ◽  
Ashesh Kumar Chowdhury ◽  
ASM Areef Ahsan ◽  
Md Zakiur Rahman ◽  
Saimun Nahar Rumana ◽  
...  

Background: Rapid diagnosis is essential for effective therapy among the patients with sepsis. Objectives: The purpose of the present study was to determine the relationship of serum levels of IL-6, IL-8 in patients with various stages of sepsis. Methodology: This case control study was conducted in the Department of Immunology at Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka from January 2015 to December 2015 for a period of one (01) year. All patients had been selected from the ICU of BIRDEM General Hospital with known clinicopathological parameters of sepsis. Serum levels of IL-6 and IL-8 were assessed using Enzyme Linked Immunosorbent Assay (ELISA) method. Results: In this study, a total of 80 subjects was enrolled of which 60 patients were with at least 2 SIRS criteria and 20 healthy age matched controls without SIRS. Significant difference was found in IL-6 and IL-8 values in the patients with bacteriological culture positive and negative group (p<0.05). AUC for IL-6 was 0.710 (95% CI 0.580-0.840), sensitivity 54.16%, specificity 59.09%, PPV 74.28% and NPV 52% with cutoff value >177pg/ml. Conclusion: Elevated levels of serum IL-6 and IL-8 is found in the patients with sepsis Bangladesh Journal of Infectious Diseases 2019;6(2):34-38


2021 ◽  
Author(s):  
Toru Hachisuga ◽  
Midori Murakami ◽  
Hiroshi Harada ◽  
Taeko Ueda ◽  
Tomoko Kurita ◽  
...  

Abstract Intra-tumoral budding (ITB) has been well demonstrated to be an independent risk factor for adverse outcomes in colorectal carcinoma. This study investigated the prognostic significance of ITB in serous ovarian carcinomas (SOCs). The medical records and slides of 84 SOCs, including 13 with neoadjuvant chemotherapy (NAC), were retrospectively reviewed. The following clinicopathological parameters were noted: age at the diagnosis, CA125 level, 2014 FIGO stage, architectural grade, nuclear grade, presence of ITB, lymphovascular space invasion (LVSI), mitotic index and lymph node metastasis. ITB was found in 65 (77.4%) of the 84 SOCs. The presence of ITB was significantly correlated with a higher level of CA125, an advanced 2014 FIGO stage, a worse architectural grade, and the presence of LVSI. The median progression-free survival (PFS) was 20 months in women with SOC with ITB and 38 months in women with SOC without ITB (P<0.01), and their median overall survival (OS) was 52 months and 72 months (P=0.05). The multivariate analysis revealed that ITB was not an independent prognostic factor. ITB is a cost-effective prognostic indicator for women with SOC and ITB in ovarian tumor tissue is considered a useful histological biomarker of the progression of SOCs.


2020 ◽  
Author(s):  
Wenhuan Li ◽  
Ji-Yu Zhang ◽  
Wen-Hui Liu ◽  
Xian-Xian Chen

Abstract Background :Anaemia is highly prevalent in gastric cancer (GC) patients. The role of initial haemoglobin levels in predicting the prognosis of GC patients treated by chemotherapy has not been well determined. Our present study aims to evaluate the relationship between the degree of anaemia and the overall survival (OS) and progression-free survival (PFS) of patients with GC. Methods: Our retrospective study enrolled 598 patients who were treated with chemotherapy when the recurrent or metastatic GCs were unsuitable for surgical resection. Univariate and multivariate analyses were performed to identify risk factors that had the potential to affect patient prognosis. Additionally, the relationship between clinicopathological characteristics, including treatment method, and degree of cancer related reduction in haemoglobin was further analysed. Results : Our results revealed that patients with HB ini level ≤ 80 g/L had a trend toward a shortened median OS and PFS ( p =0.009 and p =0.049, respectively). Interestingly, we also found that HB dec ≥30 g/L was associated with a significantly shortened median OS and PFS ( p =0.039 and p =0.001, respectively). Multivariate analysis showed that HB ini levels ≤80 g/L could be used as an independent prognostic factor for recurrent and metastatic GC. More importantly, HB dec ≥30 g/L and treatment response were also significantly associated with OS and PFS. Furthermore, the degree of haemoglobin decrease was associated with chemotherapy including platinum and the number of chemotherapy cycles. Conclusion : Our study concludes that the initial degree of anaemia and a decrease in haemoglobin of ≥ 30 g/L can serve as biomarkers to predict prognosis in recurrent or metastatic GC patients, while chemotherapy treatment rather than red blood cell (RBC) transfusion can improve their prognosis. Additionally, platinum should not be recommended for treating severely anaemic GC patients.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12605
Author(s):  
Tongtong Zhang ◽  
Suyang Yu ◽  
Shipeng Zhao

Background Gastric cancer (GC) is the most prevalent malignancy among the digestive system tumors. Increasing evidence has revealed that lower mRNA expression of ANXA9 is associated with a poor prognosis in colorectal cancer. However, the role of ANXA9 in GC remains largely unknown. Material and Methods The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases were used to investigate the expression of ANXA9 in GC, which was then validated in the four Gene Expression Omnibus (GEO) datasets. The diagnostic value of ANXA9 for GC patients was demonstrated using a receiver operating characteristic (ROC) curve. The correlation between ANXA9 expression and clinicopathological parameters was analyzed in The Cancer Genome Atlas (TCGA) and UALCAN databases. The Kaplan-Meier (K-M) survival curve was used to elucidate the relationship between ANXA9 expression and the survival time of GC patients. We then performed a gene set enrichment analysis (GSEA) to explore the biological functions of ANXA9. The relationship of ANXA9 expression and cancer immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER). In addition, the potential mechanism of ANXA9 in GC was investigated by analyzing its related genes. Results ANXA9 was significantly up-regulated in GC tissues and showed obvious diagnostic value. The expression of ANXA9 was related to the age, gender, grade, TP53 mutation, and histological subtype of GC patients. We also found that ANXA9 expression was associated with immune-related biological function. ANXA9 expression was also correlated with the infiltration level of CD8+ T cells, neutrophils, and dendritic cells in GC. Additionally, copy number variation (VNV) of ANXA9 occurred in GC patients. Function enrichment analyses revealed that ANXA9 plays a role in the GC progression by interacting with its related genes. Conclusions Our results provide strong evidence of ANXA9 expression as a prognostic indicator related to immune responses in GC.


2020 ◽  
Vol 319 (2) ◽  
pp. F335-F344 ◽  
Author(s):  
Xuan Wang ◽  
Ruijie Liu ◽  
Weijia Zhang ◽  
Deborah P. Hyink ◽  
Gokul C. Das ◽  
...  

Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We have previously shown that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3, were increased in HIVAN kidneys. Here, we demonstrate the key role of sirtuin 1 (SIRT1) deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3 in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of negative regulatory factor in podocytes stably expressing HIV-1 proviral genes, which was associated with inactivation of NF-κB p65 and a reduction in HIV-1 long terminal repeat promoter activity. In vivo, the administration of the small-molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers in Tg26 mice. Finally, we showed that the reduction in SIRT1 expression by HIV-1 is in part mediated through miR-34a expression. Together, our data provide a new mechanism of SIRT1 regulation and its downstream effects in HIV-1-infected kidney cells and indicate that SIRT1/miR-34a are potential drug targets to treat HIV-related kidney disease.


2019 ◽  
Vol 9 (2) ◽  
pp. 38
Author(s):  
Reham Nagib ◽  
Sherine Refat ◽  
Ahmed E. Eladl ◽  
Ziad Emarah ◽  
Khaled Elnaghi

Background: Expression of PD-L1 detected by immunohistochemistry can represent a new hope for cancer management. The role of PD L1 in breast cancer is still unclear. Similarly, is the role of tumor-infiltrating FOXP3 +ve regulatory T (Treg) cells where literature data are conflicting. Our study aimed to evaluate the immunohistochemical expression of PD L1 and FOXP3 in breast cancer, correlate them with clinicopathological parameters as well as evaluating their relation.Methods: This is a retrospective study carried out on 136 breast cancer specimens. Only cases with proved pathological diagnosis of infiltrating duct carcinoma of no special type (NST) were included. Tissue microarray blocks were constructed and immunostained with the polyclonal antibody for PDL1 and monoclonal antibody for FOXP3.Results: Statistically significant correlation was found between high FOXP3 and nearly all adverse prognostic factors including; grade III tumors (p = .003), basal-like subtype(p = .001), high Ki67(p = .001), negative ER status(p = .001), negative PR(p = .028), HER2 expression(p = .04), advanced stage (p = .001), and LN metastases(p = .001). For PDL1, only statistically significant correlation with high Ki67 (p = .018) and advanced stage(p = .03) was found. A statistically significant positive correlation was found between PD L1 and FOXP3(p= .001). No statistically significant correlation was found between both PDL1 and FOXP3 in relation to disease-free survival (DFS) (p = .054). PDL1, age (≥ 50 years), nodal metastases were significant predictors of relapse in breast cancer.Conclusion: The current study supports PDL1 as a predictor of relapse in breast cancer. Additionally, it highlights the synergistic role between PDL1 and FOXP3 in breast cancer microenvironment. Each can be considered as a poor prognostic marker in breast cancer. This raises a concern about the benefit of breast cancer patients from blocking of PDL1 pathway.


1985 ◽  
Vol 62 ◽  
Author(s):  
T. Sands

ABSTRACTReacted films on compound semiconductor substrates present challenging materials characterization problems which often require the application of transmission electron microscopy (TEM) techniques. In this paper, both the problem - solving potential of the TEM techniques and the limits imposed by preparation of thin film/compound semiconductor TEM specimens are discussed. Studies of the Ni/GaAs, CuCl(aq)/CdS and Pd/GaAs reactions exemplify the role of TEM in identifying and determining the spatial distribution of interface - stabilized polymorphs and new ternary phases (e.g. tetragonal Cu2S, Ni3GaAs and PdxGaAs). These examples also serve to clarify the relationship between TEM and complementary analysis techniques such as Rutherford backscattering spectrometry, Auger electron spectroscopy and glancing-angle x-ray diffraction. In particular, it is argued that a combination of (1) high-spatial-resolution information obtained by TEM and (2) an indication of the “average” behavior provided by data from a complementary characterization technique provide the minimum quality and quantity of data necessary to understand most reactions on compound semiconductor substrates.


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