Cyclo-oxygenase-2 expression is associated with mean standardised uptake value on 18F-Fluorodeoxyglucose positron emission tomography in oesophageal adenocarcinoma

Objectives: This pilot study investigated the association of four PET image features and cyclo-oxygenase-2 (COX-2) expression in patients with oesophageal adenocarcinoma. The prognostic significance of these biomarkers was also assessed. Methods: 50 consecutive patients [median age = 68 (range 47 – 84), males = 45) with oesophageal adenocarcinoma had PET/CT staging between January 2011 and July 2015. The maximum and mean standardised uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) were calculated from the primary tumour. Their association with COX-2 status was assessed using Mann-Whitney U tests. Kaplan-Meier and Cox regression analysis tested their prognostic significance. A p-value < 0.05 was considered statistically significant. Results: 32 tumours (64.0%) were COX-2 positive. There was a significant association between SUVmean and COX-2 status (p = 0.019). TLG (hazard ratio (HR) 1.001, 95 % confidence intervals (CI) 1.000 – 1.002, p = 0.018) was significantly associated with overall survival on multivariable analysis. Conclusions: This study investigated the association between PET image features and COX-2 expression in oesophageal adenocarcinoma. The preliminary results signal that a combination of TLG (calculated as product of MTV and SUVmean) and COX-2 status may be a strong and clinically important prognostic biomarker. Our research group are planning a prospective, multi-centre study to validate these findings. Advances in knowledge: Mean standardised uptake value (SUVmean) on PET imaging is associated with COX-2 expression in oesophageal adenocarcinoma.

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Prognostic significance of pathologic nodal positivity in non-metastatic patients with renal cell carcinoma who underwent radical or partial nephrectomy

Scientific Reports ◽

10.1038/s41598-021-82750-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sung Han Kim ◽

Boram Park ◽

Eu Chang Hwang ◽

Sung-Hoo Hong ◽

Chang Wook Jeong ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Partial Nephrectomy ◽

Renal Cell ◽

Cox Regression ◽

Prognostic Significance ◽

Multivariable Analysis ◽

Survival Outcomes ◽

Prognostic Impact ◽

Cox Regression Analysis

AbstractThis retrospective, five-multicenter study was aimed to evaluate the prognostic impact of pathologic nodal positivity on recurrence-free (RFS), metastasis-free (MFS), overall (OS), and cancer-specific (CSS) survivals in patients with non-metastatic renal cell carcinoma (nmRCC) who underwent either radical or partial nephrectomy with/without LN dissection. A total of 4236 nmRCC patients was enrolled between 2000 and 2012, and followed up through the end of 2017. Survival measures were compared between 52 (1.2%) stage pT1-4N1 (LN+) patients and 4184 (98.8%) stage pT1-4N0 (LN−) patients using Kaplan–Meier analysis with the log-rank test and Cox regression analysis to determine the prognostic risk factors for each survival measure. During the median 43.8-month follow-up, 410 (9.7%) recurrences, 141 (3.3%) metastases, and 351 (8.3%) deaths, including 212 (5.0%) cancer-specific deaths, were reported. The risk factor analyses showed that predictive factors for RFS, CSS, and OS were similar, whereas those of MFS were not. After adjusting for significant clinical factors affecting survival outcomes considering the hazard ratios (HR) of each group, the LN+ group, even those with low pT stage, had similar to or worse survival outcomes than the pT3N0 (LN−) group in multivariable analysis and had significantly more relationship with RFS than MFS. All survival measures were significantly worse in pT1-2N1 patients (MFS/RFS/OS/CSS; HR 4.12/HR 3.19/HR 4.41/HR 7.22) than in pT3-4N0 patients (HR 3.08/HR 2.92/HR 2.09/HR 3.73). Therefore, LN+ had an impact on survival outcomes worse than pT3-4N0 and significantly affected local recurrence rather than distant metastasis compared to LN− in nmRCC after radical or partial nephrectomy.

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Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

Biological Chemistry ◽

10.1515/hsz-2016-0177 ◽

2016 ◽

Vol 397 (12) ◽

pp. 1265-1276 ◽

Cited By ~ 14

Author(s):

Nancy Ahmed ◽

Julia Dorn ◽

Rudolf Napieralski ◽

Enken Drecoll ◽

Matthias Kotzsch ◽

...

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cox Regression ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Predictive Marker ◽

Residual Tumor ◽

Mrna Levels ◽

Serous Ovarian Cancer ◽

Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

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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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Comparison of clinicopathological features and outcomes in patients with primary leiomyosarcoma of bone and soft tissue.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e23526 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e23526-e23526

Author(s):

Alan T. Blank ◽

Charles Gusho ◽

Steven Gitelis

Keyword(s):

Soft Tissue ◽

Cox Regression ◽

Prognostic Significance ◽

Multivariable Analysis ◽

Distant Metastases ◽

High Grade ◽

Seer Database ◽

Inclusion Criteria ◽

Rare Malignancy ◽

Primary Leiomyosarcoma

e23526 Background: Leiomyosarcoma is a rare malignancy that may occur in bone. This investigation described the characteristics and outcomes of primary leiomyosarcoma of bone (PLB) compared to soft tissue leiomyosarcoma (SLMS). Methods: This study was a retrospective review using the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Continuous and categorial variables were described, and Cox regression were used to identify factors of prognostic significance. Results: Seven thousand five-hundred two patients met inclusion criteria. Seventy-four (1%) were PLB and 7428 (99%) were SLMS. On multivariable analysis for high-grade SLMS radiation (neoadjuvant: HR, 0.56; 95% CI, 0.4-0.8; p = 0.003, and adjuvant: HR, 0.75; 95% CI, 0.6-0.9; p = 0.008) and surgery (procedure specific) improved DSS, while age (HR, 1.013; 95% CI, 1.0-1.1; p < 0.001), tumor size greater than or equal to 5 cm (HR, 3.16; 95% CI, 2.3-4.2; p < 0.001), abdomen/pelvis/trunk/thorax tumors (HR, 1.31; 95% CI, 1.1-1.6; p = 0.006), and distant metastases at presentation (HR, 2.6; 95% CI, 2.1-3.3; p < 0.001) negatively influenced DSS. Conclusions: Radiation and surgery positively influence survival in high-grade SLMS while chemotherapy appears to have no benefit. Surgery alone appears to lower the mortality risk in PLB.

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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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Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

Blood ◽

10.1182/blood-2011-07-367961 ◽

2012 ◽

Vol 119 (24) ◽

pp. 5824-5831 ◽

Cited By ~ 165

Author(s):

Ana Flávia Tibúrcio Ribeiro ◽

Marta Pratcorona ◽

Claudia Erpelinck-Verschueren ◽

Veronika Rockova ◽

Mathijs Sanders ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Cox Regression ◽

Multivariable Analysis ◽

Gene Expression Signature ◽

Mutation Status ◽

Cox Regression Analysis ◽

Prognostic Effect ◽

Or Gene ◽

Acute Myeloid

Abstract The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3Amutant AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3Awild-type AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3Amutant AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3Awild-type AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

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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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