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@#Introduction: There is an increasing demand for additional techniques to diagnose and treat cancer including CRC or colorectal cancer effectively. Utilizing antibodies as biomarker could contribute to accurate diagnosis of cancer due to its high specificity and sensitivity. One of the etiologies of CRC progression was proposed as the alterations of hexosamine biosynthetic pathway which could subsequently influence the rate-limiting enzyme, glutamine-fructose-6-phosphate aminotransferase (GFAT1). These increased enzymatic activities resulted in an elevation of glucose uptake that provides nutrients facilitating the progression of cancer cells. Therefore, we attempted to determine the potential of GFAT1 as the biomarker for CRC by correlating its expression with clinicopathological features of the patients. Methods: A total of 132 10% formalin-fixed paraffin embedded tissue were retrieved. Immunohistochemistry (IHC) was performed on the tissue sections and digital images were subsequently acquired. All the images were automatedly analyzed using IHC Profiler. GFAT1 immunoreactivity in colorectal tissues was calculated using an adapted H-score formula. Clinicopathological features of the patients were statistically correlated with the status of GFAT1. Results: Colorectal adenocarcinoma tissues had the significantly highest GFAT1 H-scores with the mean of 103.18 compared to adenoma and non-tumor tissues. There have been no significant associations between clinicopathological characteristics of the patients and the status of GFAT1 except for tumor size. Conclusion: Immunoreactivity of GFAT1 was significantly different between non-tumorous tissues and adenocarcinoma as well as between adenoma and adenocarcinoma tissues. GFAT1 could serve as one of the prognostic biomarkers or useful targets.
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Head and neck squamous cell carcinoma (HNSCC), as the most common type (>90%) of head and neck cancer, includes various epithelial malignancies that arise in the nasal cavity, oral cavity, pharynx, and larynx. In 2020, approximately 878 000 new cases and 444 000 deaths linked to HNSCC occurred worldwide (Sung et al., 2021). Due to the associated frequent recurrence and metastasis, HNSCC patients have poor prognosis with a five-year survival rate of 40%-50% (Jou and Hess, 2017). Therefore, novel prognostic biomarkers need to be developed to identify high-risk HNSCC patients and improve their disease outcomes.
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Humans , Biomarkers, Tumor/genetics , Head and Neck Neoplasms/genetics , Kaplan-Meier Estimate , RNA , Squamous Cell Carcinoma of Head and Neck , Survival Analysis , Survival RateABSTRACT
Objective:To comprehensively analyze the prognostic prediction value of RNA binding protein, transcription factor gene expression and immune infiltration in hepatocellular carcinoma (HCC).Methods:Common gene sets associated with RNA-binding proteins and transcription factors were screened in TCGA ( n=365) , GSE54236 ( n=78) and GSE14520 ( n=221) datasets. Univariate Cox regression was used for primary screening. The survival regression model was constructed by LASSO-Cox. And a complex index [CIRT=(score-min)/max] was calculated. According to the median of CIRT, the HCC patients were divided into CIRT high group ( n=182) and CIRT low group ( n=182). The differences of prognosis, immune infiltration between the two groups were analyzed. Results:Of 37 prognostically relevant RNA binding protein and transcription factor genes were identified. The prognosis prediction model based on seven selected genes was determined by stepwise regression. Patients in the CIRT high group exhibited a lower percentage of macrophages in M1 ( P=0.032), macrophages in M2 ( P=0.009), resting mast cell ( P<0.001), activated NK cells ( P=0.007), and resting memory CD4 + T cells ( P<0.001), while patients in the CIRT low group showed a lower level of resting dendritic cells ( P=0.048), macrophages in M0 ( P<0.001), neutrophils ( P=0.049), follicular helper T cells ( P=0.004) and regulatory T cells ( P=0.001). GSEA analysis has shown that CIRT high groups were highly enriched in cell cycle, DNA repair pathways in TCGA and GSE14520. In the TCGA cohort, the CIRT low group had better overall survival than the CIRT high group. Analysis of 5-year follow-up data in the TCGA cohort showed that CIRT had a good predictive value for long-term survival of patients with liver cancer (area under receiver operating characteristic curve was 0.71). Conclusion:A novel prognostic index and classifier based on RNA-binding protein expression, transcription factors and immune expression profiles were developed and cross-cohort validated. CIRT could be used as an independent predictor.
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Background:Peripheral blood mononuclear cells containing an aggregate of immune competent cells,such as T lymphocytes, B cells and natural killer cells, play an important role in control or persistence of the hepatitis B virus(HBV) infection. Similarly, the expression of hepatitis B viral antigens on the surface of infected hepatocytes can invoke a cytotoxic T–cell response.Objective:To investigate the dynamic changes in hepatitis B surface antigen (HBsAg) and peripheral lymphocyte subsets of healthy donors and chronic hepatitis B patients. Methodology:Serum HBsAg was quantified by enzyme-linked immunosorbent assayaccording to the manufacturer’s guidelines. Peripheral blood lymphocyte cell phenotyping was carried out by flow cytometry for all chronic hepatitis B patients and healthy blood donors Results:The results of this study showed a significant correlation between HBsAg level and percentage of T and NK cells (r=0.366; P=0.01, r=-0.462; P=0.01,respectively). On the other hand, significance variation in peripheral blood lymphocyte percentage of T lymphocyte subsets in patients were found to be directly proportional to T cell subsets CD4+and CD8+ (P=0.001)compared with healthy blood donor controls. Conclusion:In conclusion this study highlighted the role of the HBsAg level in supressing the immune cells of the innate and adaptive immune system. Understanding the interactions between HBsAg and peripheral blood cells serves as a basis for development of HBV therapeutic vaccines and a prognostic biomarker in persistent HBV infection
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PURPOSE: 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.
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Adult , Aged , Female , Humans , Middle Aged , Young Adult , 14-3-3 Proteins/metabolism , Cell Line, Tumor , Cisplatin/therapeutic use , Disease-Free Survival , Down-Regulation , Gene Knockdown Techniques , Gene Silencing , Immunohistochemistry , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , PrognosisABSTRACT
With the clinical applications of new immunotherapies, traditional TNM staging has been unable to meet the clinical needs of curative effect predictions. It is known that the immunological features of the tumor immune microenvironment play important roles in tumor prognosis evaluations. Recently, the immunoscore system, which is based on local immune cell distribution and density, has gradually become an important indicator for prognosis evaluations and has been verified in several tumor researches. Recently, with the application of new mass flow detection and single cell sequencing technologies, the number of immune landscape studies have also been increasing, and new tumor-specific immune cell subsets have been identified. These subtypes not only provide individ-ualized immunotherapy guidelines for patients, but also provide potential new targets for the further development of new immuno-therapy strategies. This review will introduce recent research progress in this field.
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Objective To explore the expression of THBS 2 and its clinical significance in gastric cancer . Methods The mRNA and protein expression levels of THBS2 were assessed in 14 paired of gastric cancer specimen and corre-sponding normal mucosa using quantitative real-time PCR and Western blot analysis. Immunohistochemistry of TH-BS2 on a population-based tissue microarray consisting of 129 gastric cancer cases was used for evaluating the TH-BS2 prognostic significance. Kaplan-Meier method and Cox′s proportional hazards model were used in survival anal-ysis. Results Both mRNA and protein expression of THBS2 in 12 gastric cancer tissues were remarkably lower than the corresponding normal tissues among total 14 pair tissues. Consistent with the results of our Western blot, THBS2 expression was significantly inhibited in gastric cancer tissues as that in the normal controls in TMA ( P=0. 031) . Overexpression of THBS2 had a significant correlation with favorable prognosis of gastric cancer patients ( P=0. 002 ) and decreasing THBS2 expression was associated with the poor histological grade of gastric cancer his-tological grade ( P=0. 005 ) . Conclusion This study suggests THBS2 is down-regulation in gastric cancer tissue versus normal gastric tissue, and it may play a critical role in gastric cancer carcinogenesis and may be a potential prognosis predictor of gastric cancer.
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Objective:To explore the role of indoleamine-pyrrole 2,3-dioxygenase (IDO),an immunomodulatory enzyme,in renal cell carcinoma (RCC).Methods:A total of 40 patients diagnosed as RCC in the Second Xiangya Hospital were included in this study.All patients received nephrectomy.The histopathological features of samples were assessed semi-quantitatively.IDO mRNA level in RCC and non-RCC renal tissues was determined by real-time quantitative PCR (RT-qPCR).And the expression of IDO protein in endothelial cells was examined by immunohistochemistry; a Kaplan-Meier survival curves was calculated on the basis of IDO mRNA level.Results:Level of IDO mRNA in RCC samples was significantly higher than that in tumor-free samples with P＜0.001.Patients with high IDO expression had an significantly longer survival time than those with low IDO expression (P=0.01).There was a statistically significant inverse correlation between IDO and proliferation marker Ki67.Patients with high IDO level were of low Ki67 level,and vice versa (P＜0.01).Conclusion:IDO might be a prognostic biomarker for patients with RCC.
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The recent advent of "-omics" technologies have heralded a new era of personalized medicine. Personalized medicine is referred to as the ability to segment heterogeneous subsets of patients whose response to a therapeutic intervention within each subset is homogeneous. This new paradigm in healthcare is beginning to affect both research and clinical practice. The key to success in personalized medicine is to uncover molecular biomarkers that drive individual variability in clinical outcomes or drug responses. In this review, we begin with an overview of personalized medicine in breast cancer and illustrate the most encountered statistical approaches in the recent literature tailored for uncovering gene signatures.