Aberrant β-Catenin and Lef1 Expression May Predict the Clinical Outcome for Patients with Oropharyngeal Cancer

β-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin-mediated cell adhesion. Recent evidence suggests that β-catenin is also involved in other functions such as intracellular signaling via the Wnt pathway by creating a nuclear complex with members of the Lymphoid-Enhancer-Factor/T-Cell-Factor (LEF/TCF) family of transcription factors, and gene regulation that it is implicated in the development of several tumors. Little information is available on β-catenin expression and its main partner in the Wnt signaling pathway, LEF1, in oropharyngeal squamous cell carcinomas (OP-SCCs). The aim of this study is to investigate the expression of β-catenin and LEF1 expression in human primary OP-SCCs and to evaluate their clinical and prognostic significance. OP-SCCs and normal peritumoral areas were analyzed by immunohistochemistry, Western-blot and RT-PCR. β-catenin was overexpressed in tumors in comparison to normal peritumoral areas and displayed predominantly intracellular (cytosolic/nuclear) localization in 62% of the tumors. Immunoreactivity was correlated with clinicopathological parameters and long-term follow-up, and a significant association was found between protein expression and development of local recurrences (P =0.03). The OP-SCCs with poor clinical outcome, which displayed intracellular β-catenin expression, were also strongly positive for LEF1, with their co-expression statistically significant (P = 0.040). All (100%) advanced (stages 3+4) SCCs, 66.7% of the SCCs with positive lymph nodes and 80% of the SSCs that developed local recurrences were LEF1 positive. Cox regression analysis confirmed a poorer overall survival in cases with high expression of β-catenin and LEF1. Our results suggest that assessing intracellular β-catenin and LEF1 expression might help in patient risk stratification and outcome prediction, and serve as novel therapeutic targets in advanced OP-SCC.

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Pan-Cancer Analysis of the Prognostic and Immunological Role of HSF1: A Potential Target for Survival and Immunotherapy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5551036 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Fei Chen ◽

Yumei Fan ◽

Pengxiu Cao ◽

Bing Liu ◽

Jiajie Hou ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cox Regression ◽

Expression Profiles ◽

Prognostic Significance ◽

Deep Understanding ◽

Clinicopathological Parameters ◽

Cox Regression Analysis ◽

Pan Cancer

Emerging evidence revealed the significant roles of heat shock factor 1 (HSF1) in cancer initiation, development, and progression, but there is no pan-cancer analysis of HSF1. The present study first comprehensively investigated the expression profiles and prognostic significance of HSF1 and the relationship of HSF1 with clinicopathological parameters and immune cell infiltration using bioinformatic techniques. HSF1 is significantly upregulated in various common cancers, and it is associated with prognosis. Pan-cancer Cox regression analysis indicated that the high expression of HSF1 was associated with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), and kidney renal papillary cell carcinoma (KIRP) patients. The methylation of HSF1 DNA was decreased in most cancers and negatively correlated with the HSF1 expression. Increased phosphorylation of S303, S307, and S363 in HSF1 was observed in some cancers. HSF1 remarkably correlated with the levels of infiltrating cells and immune checkpoint genes. Our pan-cancer analysis provides a deep understanding of the functions of HSF1 in oncogenesis and metastasis in different cancers.

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The expression of miR-211-5p in atherosclerosis and its influence on diagnosis and prognosis

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02187-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yanxia Zhang ◽

Huiyun Wang ◽

Yu Xia

Keyword(s):

Roc Curve ◽

Cox Regression ◽

Survival Curve ◽

Prognostic Significance ◽

Significant Negative Correlation ◽

Diagnostic Value ◽

Expression Level ◽

Healthy Controls ◽

Cox Regression Analysis ◽

Diagnosis And Prognosis

Abstract Background The purpose of this study was to evaluate the diagnostic and prognostic significance of miR-211-5p in atherosclerosis (AS) by detecting the expression level in serum of patients with AS. Methods A total of 85 healthy controls and 90 asymptomatic AS patients participated in this study. The expression level of miR-211-5p in all subjects were measured by qRT-PCR. Spearman correlation coefficient was used to evaluate the correlation of miR-211-5p with CRP and CIMT. The ROC curve was established to assess the diagnostic value of miR-211-5p in AS. The Kaplan–Meier survival curve and multivariate COX regression analysis were used to evaluate the prognostic significance of miR-211-5p in AS. Results The expression levels of miR-211-5p in AS patients were significantly lower than in healthy controls (P < 0.001), and miR-211-5p showed a significant negative correlation with CRP (r = − 0.639, P < 0.001) and CIMT (r = − 0.730, P < 0.001). The AUC of the ROC curve was 0.900, the specificity and the sensitivity were 84.7% and 78.9%, respectively, which indicating that miR-211-5p had diagnostic value for AS. Survival analysis showed that patients with low miR-211-5p expression were more likely to have cardiovascular end-point events (Log rank P = 0.013). Conclusion Serum miR-211-5p could be used as a new biomarker for the diagnosis of AS, and the low expression of miR-211-5p is associated with the poor prognosis of AS.

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Expression and Clinical Significance of Serum Exosomal miR-375 in Patients with Gastric Cancer

Tobacco Regulatory Science ◽

10.18001/trs.7.5.1.162 ◽

2021 ◽

Vol 7 (5) ◽

pp. 3896-3904

Author(s):

Daoting Deng ◽

Hong Zhang ◽

Junxi Liu ◽

Lina Ma ◽

Xinrui Lei ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Cox Regression ◽

Prognostic Significance ◽

Cox Regression Analysis ◽

Healthy Group ◽

Cancer Group ◽

Kaplan Meier ◽

Gastric Cancer Patients ◽

Gastric Cancer Group

To explore exosomal miR-375 expression in gastric cancer patients and its relationship with patient prognosis. A total of 53 patients diagnosed with gastric cancer in our hospital from May 2014 to May 2016 were included as the gastric cancer group, and 46 healthy women who came to our hospital for physical examination during the same period were enrolled as the healthy group. Exosomal miR-375 expression level was detected using qRT-PCR, and the diagnostic performance and prognostic significance of exosomal miR-375 in gastric cancer were explored. The gastric cancer group showed increased exosomal miR-375 expression than the healthy group (P< 0.05); Kaplan-Meier survival analysis exhibited that serum exosomal miR-375 has an AUC of 0.778, sensitivity of 69.57%, and specificity of 75.47%, whereas Cox regression analysis showed that the miR-375 expression in exosomes was an independent risk factor affecting the prognosis of gastric cancer patients (P< 0.05). Patient with gastric cancer showed upregulated miR-375 expression in serum exosomes. Serum exosomal miR-375 was found to has positive sensitivity and specificity in the diagnosis of gastric cancer, which may be associated with poor prognosis of gastric cancer patients.

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Diagnostic and prognostic significance of miR-451a in patients with atherosclerosis

Vascular ◽

10.1177/17085381211058571 ◽

2021 ◽

pp. 170853812110585

Author(s):

Baizhi Wang ◽

Xingliang Duan ◽

Qing Xu ◽

Yani Li

Keyword(s):

Operating Characteristic ◽

Cox Regression ◽

Prognostic Biomarker ◽

Prognostic Significance ◽

High Sensitivity ◽

Roc Curves ◽

Cox Regression Analysis ◽

Chi Squared ◽

Cardiovascular Endpoint ◽

Inflammatory Vascular Disease

Objectives Atherosclerosis (AS) is a chronic inflammatory vascular disease. This study aimed to detect the expression level of miR-451a and investigate the diagnostic and prognostic values of miR-451a for AS patients. Methods The relative expression of miR-451a was assessed by qRT-PCR. Comparison of groups was analyzed with the t-test and chi-squared test. Pearson analysis was used to validate the correlation of miR-451 with CRP and CIMT. The receiver operating characteristic (ROC) curves, K-M analysis, and Cox regression analysis were conducted to explore the roles of miR-451a in diagnosing AS patients and predicting outcomes of AS patients. Results The expression of miR-451a was significantly decreased in the serum of AS patients. The results of Pearson analysis showed the expression of miR-451a was negatively correlated with CRP and CIMT. The data of ROC proposed miR-451a could differentiate AS patients from healthy individuals with high sensitivity and specificity. K-M analysis and Cox regression showed miR-451a might be an independent biomarker of suffering cardiovascular endpoint diseases in AS patients. The expression of miR-451a was obviously inhibited in AS patients with cardiovascular endpoint events. Conclusion Deregulation of miR-451a might be associated with the development of AS. MiR-451a might be used as a promising diagnostic and prognostic biomarker for clinical treatment of AS patients.

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Prognostic Significance of PD-L1 and mTOR Expression in Oral Squamous Cell Carcinoma

Journal of Health Science and Medical Research ◽

10.31584/jhsmr.2020745 ◽

2020 ◽

Author(s):

Nattinee Charoen ◽

Kitti Jantharapattana ◽

Paramee Thongsuksai

Keyword(s):

Squamous Cell Carcinoma ◽

Regression Analysis ◽

Prognostic Factors ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cox Regression ◽

Prognostic Significance ◽

P Value ◽

Cox Regression Analysis

Objective: Programmed cell death ligand 1 (PD-L1) and mammalian target of rapamycin (mTOR) are key players in host immune evasion and oncogenic activation, respectively. Evidence of the prognostic role in oral squamous cell carcinoma (OSCC) is conflicting. This study examined the associations of PD-L1 and mTOR expression with 5-year overall survival in OSCC patients. Material and Methods: The expressions of PD-L1 and mTOR proteins were immunohistochemically evaluated on tissue microarrays of 191 patients with OSCC who were treated by surgery at Songklanagarind Hospital, Thailand from 2008 to 2011. Cox regression analysis was used to determine independent prognostic factors. Results: PD-L1 expression was observed in 14.1% of cases while mTOR expression was present in 74.3% of cases. Females were more likely to have tumors with PD-L1 (p-value=0.007) and mTOR expressions (p-value=0.003) than males. In addition, lower clinical stage and well differentiated tumor are more likely to have mTOR expression (p-value= 0.038 and p-value<0.001, respectively). Cox regression analysis showed that age, tumor stage, nodal stage, combined surgical treatment with radiation or chemoradiation therapy, surgical margin status, PD-L1 expression and mTOR expression are independent prognostic factors. High PD-L1 expression (hazard ratio (HR) 3.14, 95% confidence interval (CI), 1.26–7.79) and high mTOR expression (HR 1.69, 95% CI, 1.00–2.84) are strong predictors of poor outcome. Conclusion: A proportion of OSCC expressed PD-L1 and mTOR proteins. Expression of PD-L1 and mTOR proteins are strong prognostic factors of OSCC.

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Prognostic Significance of Chest Imaging by LUS and CT in COVID-19 Inpatients: The ECOVID Multicenter Study

Respiration ◽

10.1159/000518516 ◽

2021 ◽

pp. 1-10

Author(s):

Claudio Tana ◽

Fabrizio Ricci ◽

Maria Gabriella Coppola ◽

Cesare Mantini ◽

Fulvio Lauretani ◽

...

Keyword(s):

Hospital Mortality ◽

Cox Regression ◽

Pearson Correlation ◽

Prognostic Significance ◽

Chest Ct ◽

Lung Damage ◽

Chest Imaging ◽

Gold Standard Method ◽

Cox Regression Analysis ◽

Total Score Range

Background: Point-of-care lung ultrasound (LUS) score is a semiquantitative score of lung damage severity. High-resolution computed tomography (HRCT) is the gold standard method to evaluate the severity of lung involvement from the novel coronavirus disease (COVID-19). Few studies have investigated the clinical significance of LUS and HRCT scores in patients with COVID-19. Therefore, the aim of this study was to evaluate the prognostic yield of LUS and of HRCT in COVID-19 patients. Methods: We carried out a multicenter, retrospective study aimed at evaluating the prognostic yield of LUS and HRCT by exploring the survival curve of COVID-19 inpatients. LUS and chest CT scores were calculated retrospectively by 2 radiologists with >10 years of experience in chest imaging, and the decisions were reached in consensus. LUS score was calculated on the basis of the presence or not of pleural line abnormalities, B-lines, and lung consolidations. The total score (range 0–36) was obtained from the sum of the highest scores obtained in each region. CT score was calculated for each of the 5 lobes considering the anatomical extension according to the percentage parenchymal involvement. The resulting overall global semiquantitative CT score was the sum of each single lobar score and ranged from 0 (no involvement) to 25 (maximum involvement). Results: One hundred fifty-three COVID-19 inpatients (mean age 65 ± 15 years; 65% M), including 23 (15%) in-hospital deaths for any cause over a mean follow-up of 14 days were included. Mean LUS and CT scores were 19 ± 12 and 10 ± 7, respectively. A strong positive linear correlation between LUS and CT scores (Pearson correlation r = 0.754; R2 = 0.568; p < 0.001) was observed. By ROC curve analysis, the optimal cut-point for mortality prediction was 20 for LUS score and 4.5 for chest CT score. According to Kaplan-Meier survival analysis, in-hospital mortality significantly increased among COVID-19 patients presenting with an LUS score ≥20 (log-rank 0.003; HR 9.87, 95% CI: 2.22–43.83) or a chest CT score ≥4.5 (HR 4.34, 95% CI: 0.97–19.41). At multivariate Cox regression analysis, LUS score was the sole independent predictor of in-hospital mortality yielding an adjusted HR of 7.42 (95% CI: 1.59–34.5). Conclusion: LUS score is useful to stratify the risk in COVID-19 patients, predicting those that are at high risk of mortality.

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Construction and Validation of a Metabolic Reprogramming Related Prognostic Model for Hepatocellular Carcinoma

10.21203/rs.3.rs-97188/v1 ◽

2020 ◽

Author(s):

Xiaohong - Liu ◽

Qian - Xu ◽

Zi-Jing - Li ◽

Bin - Xiong

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Risk Score ◽

Prognostic Model ◽

Cox Regression ◽

Expression Profiles ◽

Prognostic Significance ◽

Metabolic Reprogramming ◽

Cox Regression Analysis ◽

Metabolic Genes

Abstract BackgroundMetabolic reprogramming is an important hallmark in the development of malignancies. Numerous metabolic genes have been demonstrated to participate in the progression of hepatocellular carcinoma (HCC). However, the prognostic significance of the metabolic genes in HCC remains elusive. MethodsWe downloaded the gene expression profiles and clinical information from the GEO, TCGA and ICGC databases. The differently expressed metabolic genes were identified by using Limma R package. Univariate Cox regression analysis and LASSO (Least absolute shrinkage and selection operator) Cox regression analysis were utilized to uncover the prognostic significance of metabolic genes. A metabolism-related prognostic model was constructed in TCGA cohort and validated in ICGC cohort. Furthermore, we constructed a nomogram to improve the accuracy of the prognostic model by using the multivariate Cox regression analysis.ResultsThe high-risk score predicted poor prognosis for HCC patients in the TCGA cohort, as confirmed in the ICGC cohort (P < 0.001). And in the multivariate Cox regression analysis, we observed that risk score could act as an independent prognostic factor for the TCGA cohort (HR (hazard ratio) 3.635, 95% CI (confidence interval)2.382-5.549) and the ICGC cohort (HR1.905, 95%CI 1.328-2.731). In addition, we constructed a nomogram for clinical use, which suggested a better prognostic model than risk score.ConclusionsOur study identified several metabolic genes with important prognostic value for HCC. These metabolic genes can influence the progression of HCC by regulating tumor biology and can also provide metabolic targets for the precise treatment of HCC.

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Prognostic Significance and Gene Co-Expression Network of PLAU and PLAUR in Gliomas

Frontiers in Oncology ◽

10.3389/fonc.2021.602321 ◽

2022 ◽

Vol 11 ◽

Author(s):

Junhong Li ◽

Huanhuan Fan ◽

Xingwang Zhou ◽

Yufan Xiang ◽

Yanhui Liu

Keyword(s):

Cox Regression ◽

Prognostic Significance ◽

High Expression ◽

Lower Grade ◽

Tumor Type ◽

Who Grade ◽

Cox Regression Analysis ◽

Online Databases ◽

Type Plasminogen Activator ◽

Primary Glioma

The urokinase-type plasminogen activator(PLAU) and its receptor PLAUR participate in a series of cell physiological activities on the extracellular surface. Abnormal expression of PLAU and PLAUR is associated with tumorigenesis. This study aims to evaluate the prognostic value of PLAU/PLAUR transcription expression in glioma and to explore how they affect the generation and progression of glioma. In this study, online databases are applied, such as Oncomine, GEPIA, CGGA, cBioPortal, and LinkedOmics. Overexpression of PLAU/PLAUR was found to be significantly associated with clinical variables including age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. PLAU and PLAUR had a high correlation in transcriptional expression levels. High expression of PLAU and PLAUR predicted a poor prognosis in primary glioma and recurrent glioma patients, especially in lower grade gliomas. Cox regression analysis indicated that high expression of PLAU and PLAUR were independent prognostic factors for shorter overall survival in glioma patients. In gene co-expression network analysis PLAU and PLAUR and their co-expression genes were found to be involved in inflammatory activities and tumor-related signaling pathways. In conclusion, PLAU and PLAUR could be promising prognostic biomarkers and potential therapeutic targets of glioma patients.

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Interleukin-4 Promoter Polymorphisms: A Genetic Prognostic Factor for Survival in Metastatic Renal Cell Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2006.07.8154 ◽

2007 ◽

Vol 25 (7) ◽

pp. 845-851 ◽

Cited By ~ 33

Author(s):

Thomas Kleinrath ◽

Christoph Gassner ◽

Peter Lackner ◽

Martin Thurnher ◽

Reinhold Ramoner

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Clinical Course ◽

Prognostic Significance ◽

Interleukin 4 ◽

Promoter Polymorphisms ◽

Cox Regression Analysis ◽

Metastatic Rcc

Purpose Renal cell carcinoma (RCC) is considered a cytokine-responsive tumor. The clinical course of a patient may thus be influenced by the patient's capacity to produce distinct cytokines. Therefore, cytokine gene polymorphisms in RCC patients were analyzed to determine haplotype combinations with prognostic significance. Patients and Methods A selection of 21 single nucleotide polymorphisms within the promoter regions of 13 cytokine genes were analyzed in a cross-sectional single-center study of 80 metastatic RCC patients. Univariate and multivariate analyses and the Cox forward-stepwise regression model were chosen to assess genetic risk factors. Results Multivariate Cox regression analysis confirmed by a bootstrap technique identified the heterozygous IL4 genotype −589T−33T/−589C−33C as an independent prognostic risk factor (risk ratio, 3.1; P < .01; 95% CI, 1.4 to 6.9; adjusted for age, sex, and nuclear grading) in metastatic RCC patients. IL4 haplotype −589T−33T and −589C−33C were found with a frequency of 0.069 and 0.925, respectively, which represents a two-fold decrease of IL4 haplotype −589T−33T (P < .01) and an increase of IL4 haplotype −589C−33C frequency (P < .05) in metastatic RCC compared with other white reference study populations. The median overall survival was decreased 3.5-fold (P < .05) in heterozygote patients carrying IL4 haplotype −589T−33T and −589C−33C (3.78 months) compared with patients homozygote for IL4 haplotype −589C−33C (13.44 months). In addition, a linkage disequilibrium between the IL4 gene and the KIF3A gene was detected. Conclusion Our findings indicate that IL4 promoter variants influence prognosis in patients with metastatic RCC and suggest that genetically determined interleukin-4 (IL-4) production affects the clinical course of the disease possibly through regulation of immune surveillance.

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CIP4 Expression is Associated With The Prognosis in Colorectal Cancer

10.21203/rs.3.rs-95046/v1 ◽

2020 ◽

Author(s):

Keqian Zhang ◽

Tianqi Mao ◽

Zhicheng He ◽

Xiaojiao Wu ◽

Yu Peng ◽

...

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Prognostic Significance ◽

Lymphatic Invasion ◽

Chi Square ◽

Interacting Protein ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Chi Square Test ◽

Student’S T

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.

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