scholarly journals Prognostic significance of preoperative plasma fibrinogen levels in primary gastrointestinal stromal tumours: a retrospective cohort study

2019 ◽  
Author(s):  
Shibo Song ◽  
Xianglong Cao ◽  
Hongda Pan ◽  
Maolin Hu ◽  
Qiuxia Yan ◽  
...  

Abstract Background Improved prediction of prognosis for gastrointestinal stromal tumours (GIST) has become increasingly important since the introduction of small molecule tyrosine kinase inhibitors. Here, we aimed to evaluate the prognostic significance of preoperative plasma fibrinogen (Fib) levels in patients with primary GIST and to analyze their correlations with clinicopathological characteristics.Methods A total of 201 previously untreated patients with primary GIST who had underwent radical surgery at our institution between October 2004 and July 2018 were enrolled. Patient demographics, clinicopathological characteristics, preoperative plasma Fib levels and recurrence-free survival (RFS) were analyzed. The optimal cut-off value for Fib levels was calculated using receiver operating characteristic curve analysis. RFS, the primary endpoint, was calculated by the Kaplan–Meier method and compared by the log-rank test. Univariate and multivariate Cox regression models were calculated.Results Patients in high Fib group had a shorter RFS compared with low Fib group (P < 0.001). In multivariate analysis, high preoperative plasma Fib levels were detected as an independent adverse prognostic factor (P = 0.004, hazard ratio 3.443, 95% confidence interval 1.498‒7.916). Furthermore, high preoperative plasma Fib levels also indicated a poor prognosis within the modified National Institutes of Health (mNIH) high-risk subgroup (P = 0.013). In addition, preoperative plasma Fib levels were showed a positive correlation with several prognostic factors, and even linearly with tumour size (Spearman correlation coefficient [ r ] = 0.411, P < 0.001).Conclusions High preoperative plasma Fib levels may indicate a poor prognosis in patients with primary GIST. As a cost-effective biomarker, preoperative assessment of plasma Fib levels may help to further risk stratification for patients with mNIH high-risk GIST and instruct the application of target therapy.

2020 ◽  
Author(s):  
Shibo Song ◽  
Xianglong Cao ◽  
Hongda Pan ◽  
Maolin Hu ◽  
Qiuxia Yan ◽  
...  

Abstract Background Improved prediction of prognosis for gastrointestinal stromal tumours (GISTs) has become increasingly important since the introduction of small molecule tyrosine kinase inhibitors. Here, we aimed to evaluate the prognostic significance of preoperative plasma fibrinogen (Fib) levels in patients with primary GISTs and to analyse their correlations with clinicopathological characteristics. Methods A total of 201 previously untreated patients with primary GISTs who had undergone radical surgery at our institution between October 2004 and July 2018 were enrolled. Patient demographics, clinicopathological characteristics, preoperative plasma Fib levels and recurrence-free survival (RFS) were analysed. The optimal cut-off value for Fib levels was calculated using time-dependent receiver operating characteristic curve analysis. RFS, the primary endpoint, was calculated by the Kaplan–Meier method and compared by the log-rank test. Univariate and multivariate Cox regression models were calculated. Results Patients in the high Fib group had a shorter RFS than those in the low Fib group (P < 0.001). In multivariate analysis, high preoperative plasma Fib levels were detected as an independent adverse prognostic factor (P = 0.008, hazard ratio 3.136, 95% CI 1.356‒7.256). Furthermore, high preoperative plasma Fib levels also indicated a poor prognosis within the modified National Institutes of Health (mNIH) high-risk subgroup (P = 0.041). In addition, preoperative plasma Fib levels showed a positive correlation with several prognostic factors and even a linear relationship with tumour size (Spearman correlation coefficient [ r ] = 0.411, P < 0.001). Conclusions High preoperative plasma Fib levels may indicate a poor prognosis in patients with primary GISTs. As a cost-effective biomarker, preoperative assessment of plasma Fib levels may help to further risk stratify patients with mNIH high-risk GISTs and instruct the application of targeted therapy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Wenkai Ni ◽  
Saiyan Bian ◽  
Mengqi Zhu ◽  
Qianqian Song ◽  
Jianping Zhang ◽  
...  

PurposeUbiquitin-specific proteases (USPs), as a sub-family of deubiquitinating enzymes (DUBs), are responsible for the elimination of ubiquitin-triggered modification. USPs are recently correlated with various malignancies. However, the expression features and clinical significance of USPs have not been systematically investigated in hepatocellular carcinoma (HCC).MethodsGenomic alterations and expression profiles of USPs were investigated in CbioPortal and The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) dataset. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were conducted to establish a risk signature for HCC prognosis in TCGA LIHC cohort. Subsequently, Kaplan-Meier analysis, receiver operating characteristic (ROC) curves and univariate/multivariate analyses were performed to evaluate the prognostic significance of the risk signature in TCGA LIHC and international cancer genome consortium (ICGC) cohorts. Furthermore, we explored the alterations of the signature genes during hepatocarcinogenesis and HCC progression in GSE89377. In addition, the expression feature of USP39 was further explored in HCC tissues by performing western blotting and immunohistochemistry.ResultsGenomic alterations and overexpression of USPs were observed in HCC tissues. The consensus analysis indicated that the USPs-overexpressed sub-Cluster was correlated with aggressive characteristics and poor prognosis. Cox regression with LASSO algorithm identified a risk signature formed by eight USPs for HCC prognosis. High-risk group stratified by the signature score was correlated with advanced tumor stage and poor survival HCC patients in TCGA LIHC cohort. In addition, the 8-USPs based signature could also robustly predict overall survival of HCC patients in ICGC(LIRI-JP) cohort. Furthermore, gene sets enrichment analysis (GSEA) showed that the high-risk score was associated with tumor-related pathways. According to the observation in GSE89377, USP39 expression was dynamically increased with hepatocarcinogenesis and HCC progression. The overexpression of USP39 was further determined in a local HCC cohort and correlated with poor prognosis. The co-concurrence analysis suggested that USP39 might promote HCC by regulating cell-cycle- and proliferation- related genes.ConclusionThe current study provided a USPs-based signature, highlighting its robust prognostic significance and targeted value for HCC treatment.


2020 ◽  
Author(s):  
Wenli Xie ◽  
Naifu Liu ◽  
Xiangyu Wang ◽  
Wenyan Xie ◽  
Dapeng Li ◽  
...  

Abstract Background. Wilms’ tumor 1‐associating protein (WTAP) was previously reported to play critical roles in the tumorigenesis of different malignancies, and its expression level has been linked to a poor prognosis of several cancers. We evaluated the role of WTAP in endometrial carcinoma (EC) using publicly available data from The Cancer Genome Atlas (TCGA). Methods. The relationship between WTAP expression and clinical characteristics was assessed with the Wilcoxon signed‐rank test and logistic regression. Clinical factors associated with prognosis were evaluated using Cox regression analysis and Kaplan-Meier method. Gene set enrichment analysis (GSEA) was conducted using TCGA dataset. Results. Our results revealed that WTAP was significantly up-regulated in EC. Increased WTAP expression in EC was significantly associated with high-grade tumor (odds ratio [OR] = 2.126) and high-risk histology (OR = 1.915) (all P < 0.05). Patients with high WTAP expression had a worse overall survival (OS) (hazard ratio [HR] = 2.868, 95% confidence interval [CI] = 1.259-6.532; P = 0.0087) and recurrence-free survival (RFS) (HR =3.148, 95% CI = 1.372-7.220; P = 0.004) than those with low WTAP expression. Multivariate analysis showed that WTAP expression remained an independent predictor of OS and RFS. Furthermore, GSEA showed that wnt/β-catenin signaling pathway was differentially enriched in WTAP high expression phenotype. Conclusions. WTAP was over-expressed in EC. WTAP expression was an independent predictor of poor OS and RFS in EC, and it was associated with advanced grade, high-risk EC. Moreover, the wnt/β-catenin signaling pathway might be the key process regulated by WTAP in EC.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16166-e16166
Author(s):  
Jennifer Dominguez ◽  
Bonnie Macario ◽  
Rixci Ramirez ◽  
Mario Daniel Castro

e16166 Background: Worldwide, every year, there are nearly 905,000 patients diagnosed with liver cancer; it is the sixth most common malignancy and the third most lethal malignancy. Almost three quarters of new patients live in areas with low and medium-income country. Guatemala has the highest mortality and incidence of liver cancer. Objectives: Describe the clinical characteristics, main risk factors, treatment and outcomes of patients with hepatocarcinoma (HCC) in Guatemala. Methods: A retrospective review was performed among patients with HCC from January 2002 to December 2019 in the Instituto Guatemalteco de Seguridad Social (IGSS). Kaplan Meier curves, Cox regression and log-rank test were used to calculate overall survival (OS) and mortality. Results: 140 patients with HCC were analyzed, 114 women and 26 men with a median age of 60 years (20 - 99), 102 patients (73%) have history of excessive alcohol consumption and 11 (8%) has history of chronic hepatitis B or C virus infection. All of the patients have liver cirrhosis, Child-Pugh A 100 patients (71%), B 34 (24%) and C 6 (5%). 10 patients (7%) have HCC BCLC A, 0 (0%) BCLC B, 121 (81%) BCLC C and 9 (6%) BCLC D. All patients with HCC BCLC A received surgical treatment with a median OS of 123 months (95% CI 89 - 156 p < 0.001). 122 patients (89%) received target therapy with Sorafenib with a median OS of 17 months (95% CI 12 - 21 p < 0.001) and 8 patients (6%) underwent to chemoembolization with a median OS of 32 months (95% CI 12 - 52 p < 0.001). At this time, 111 patients (79%) died from the disease, 11 (8%) are alive with the disease and 8 (6%) are alive without disease. Conclusions: The most frequent risk factor for HCC is the excessive alcohol consumption, survival of patients with HCC are associated with treatment at the beginning of the disease.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Menghui Wu ◽  
Yuchen Pan ◽  
Zhifang Jia ◽  
Yueqi Wang ◽  
Na Yang ◽  
...  

Background. Radical gastrectomy with D2 lymphadenectomy is recognized as the standard treatment for resectable advanced gastric cancer. Preoperative fibrinogen and albumin measurements may bring clinical benefits in terms of providing advanced notice of a poor prognosis or recurrence in patients undergoing radical resection. The aim of this study was to identify markers that are predictive of a poor prognosis prior to surgery. Methods. Eight hundred forty-two consecutive patients who underwent curative radical gastrectomy at our hospital between 2008 and 2012 were retrospectively reviewed. Based on plasma fibrinogen and serum albumin levels, preoperative fibrinogen and albumin scores (Fib-Alb scores) were investigated, and the prognostic significance was determined. Results. The patients were classified according to a Fib-Alb score of 0 (n=376), 1 (n=327), or 2 (n=139). When the correlation between the response rate and the change in the Fib-Alb score was investigated, the response rate was significantly lower in patients with an increased Fib-Alb score than in the other patients. In the survival analysis, patients in the Fib-Alb high-score group exhibited significantly worse recurrence-free survival (RFS) (P=0.030) than patients in the other groups. A multivariate analysis using clinical stage and the change in the Fib-Alb score as covariates revealed that a change in the Fib-Alb score (Fib-Alb score 1, HR: 1.31, 95% CI: 1.03-1.66, P=0.028; Fib-Alb score 2, HR: 1.61, 95% CI: 1.20-2.17, P=0.001) was a significant independent predictive factor for RFS. Conclusions. The prognosis of patients with high fibrinogen and low albumin levels is poor. The Fib-Alb score was shown to be an independent prognostic factor for postoperative recurrence in gastric cancer patients who underwent radical gastrectomy.


2002 ◽  
Vol 20 (4) ◽  
pp. 941-950 ◽  
Author(s):  
Alexander Stojadinovic ◽  
Ronald A. Ghossein ◽  
Axel Hoos ◽  
Aviram Nissan ◽  
David Marshall ◽  
...  

PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters. PATIENTS AND METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression. RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P = .005).The phenotype Ki-67(−)p53(−)mdm-2(+)cyclinD1(−)Bcl-2(−)p21(−)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P = .01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue. CONCLUSION: Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5536-5536
Author(s):  
L. Randall-Whitis ◽  
B. J. Monk ◽  
E. S. Han ◽  
K. Darcy ◽  
R. A. Burger ◽  
...  

5536 Background: Extensive tumor angiogenesis has correlated with poorer progression-free and overall survival in cervical cancer; however, specific markers of angiogenesis have not been studied prospectively. Methods: Cervical cancer patients with high-risk features on radical hysterectomy were eligible for randomization to adjuvant pelvic irradiation ± radiosensitizing platinum. Following central pathology review, formalin-fixed, paraffin-embedded tumors were sectioned into 4-micron specimens. Semi-quantitative immunohistochemisty (IHC) was performed using previously validated antibodies against mutant p53 (mp53), vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP-1), and endothelial markers CD 31 and CD 105. Tumoral histoscores (HS) were calculated for mp53 and VEGF using the formula: [% cells positive × (intensity +1)], with a 5% threshold for positivity and intensity ranging 1–4+ (3+ = intensity of positive control). Intensity scores (0–4+) were assigned to TSP-1 specimens referencing the positive control (3+). MVD “hotspots” were counted in a 20X high-power field. HS and MVD counts were considered as continuous variables and TSP-1 intensity as an ordinal variable. Associations between markers were determined by Pearson’s and Spearman’s correlation tests, between markers and clinico-pathologic variables by Wilcoxon rank test, and between markers and survival by Cox regression modeling. Results: One hundred seventy-six specimens were analyzed. Acquisition of mp53 and increased VEGF expression were associated with increased MVD assessed by both CD31 (p=0.08 and p=0.002, respectively) and CD105 (p=0.02 and p=0.012, respectively). Statistically significant associations between markers and high-risk pathologic factors included: low-level TSP-1 and high CD-105 counts with lymph node metastases; high VEGF scores with advanced stage, non-squamous histologic subtype, and depth of tumor invasion; and high CD 31 counts with parametrial metastases. Survival analysis is currently being performed. Conclusions: Angiogenesis occurs early in cervical carcinogenesis, and may be a rational target for biologic therapy in cervical cancer. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 403-403
Author(s):  
Nabil Adra ◽  
Sandra K. Althouse ◽  
Rafat Abonour ◽  
Mohammad Issam Abu Zaid ◽  
Hao Liu ◽  
...  

403 Background: Rate of serum TM decline is prognostic in patients (pts) with GCT receiving first-line chemotherapy. We investigated the prognostic value of TM decline in rGCT treated with HDCT+peripheral-blood stem-cell transplant (PBSCT). Methods: 462 consecutive pts with rGCT treated with HDCT+PBSCT at Indiana University between 1/2004-1/2019. All pts were planned for 2 consecutive HDCT courses with carboplatin+etoposide per protocol (N Engl J Med 2007;357:340-8). Pts with elevated AFP and/or hCG were included (N=347). Slope and half-life (T1/2) were calculated for weekly AFP+hCG during HDCT starting with peak value at days 1-7 to avoid interference from lysis. T1/2 AFP≤7 days and hCG≤3 days were categorized satisfactory (SAT). Progression-free (PFS) and overall survival (OS) were compared for SAT vs unsatisfactory (UNSAT) using log-rank test and analyzed using Kaplan-Meier. Uni- and multivariable analysis using Cox regression model was performed. Results: 347 pts had elevated TM: 312 had non-seminoma and 35 had seminoma. Median age was 31 (range, 17-58). Primary site: testis (292), mediastinum (26), retroperitoneum/other (29). Metastatic sites included retroperitoneum (277), lung (233), liver (83), brain (77), and bone (21). At initiation of HDCT, 77 pts had elevated AFP, 222 elevated hCG, and 48 elevated both AFP+hCG. Median AFP 9 (1-21,347) and hCG 113 (1-178,140). 314 pts (91%) completed 2 planned cycles of HDCT. Overall, 46/347 pts had SAT decline (13 for AFP; 30 for hCG; 3 for both). Pts with SAT TM decline had superior outcomes compared to UNSAT: 2-yr PFS 69% vs 45% (p=0.006) and 2-yr OS 75% vs 51% (p=0.006). When evaluating each TM separately, SAT decline in hCG had superior outcomes vs UNSAT: 2-yr PFS 74% vs 47% (p=0.002). There was statistically non-significant difference for AFP: 2-yr PFS 48% vs 42% (p=0.65). In univariable analysis, UNSAT decline of hCG, but not AFP, was an adverse prognostic factor for PFS: HR=2.51 (95% CI, 1.40-4.51); p=0.002. Multivariable analysis will be presented. Conclusions: SAT rate of TM decline, particularly in hCG, predicts superior outcomes in rGCT undergoing HDCT+PBSCT. Pts with UNSAT TM decline are at higher risk for relapse and death.


Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4671-4675 ◽  
Author(s):  
Chung-Che Chang ◽  
Jennifer Lorek ◽  
Daniel E. Sabath ◽  
Ying Li ◽  
Christopher R. Chitambar ◽  
...  

In this study, we evaluated the prognostic significance of multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4) expression in B-cell chronic lymphocytic leukemia (B-CLL). Our results demonstrated that the absence of MUM1/IRF4 expression showed the highest relative risk among the factors analyzed in determining the probability for death in patients with B-CLL using univariate and multivariate Cox regression analysis. Patients without MUM1/IRF4 expression had significantly worse overall survival than did those with MUM1/IRF4 expression (52% cumulative survival, 63 months vs not reached, Kaplan-Meier survival analysis; P < .03, log-rank test). Patients with MUM1/IRF4 expression were more likely to have disease at low Rai stage and interstitial/nodular marrow involvement. Furthermore, only 1 of 11 patients with MUM1/IRF4 expression and interstitial/nodular marrow involvement died during a 100-month follow-up. Our results suggest that B-CLL with expression of MUM1/IRF4, indicative of postgerminal center origin, has a more favorable clinical course and that MUM1/IRF4 is an important prognostic marker in B-CLL.


2021 ◽  
Author(s):  
xinwen zhang ◽  
Hao Xiong ◽  
Jialin Duan ◽  
Xiaomin Chen ◽  
Yang Liu ◽  
...  

Abstract Background: Acute myeloid leukemia (AML) is one of the common malignant diseases of hematopoietic system. Paxillin ( PXN ) is an important part of focal adhesions (FAs), which is related to the poor prognosis of many kinds of malignant tumors. However, no research has focused on the expression of PXN in AML. We aimed to investigate the expression of PXN in AML and its prognostic significance. Methods: Using GEPIA and UALCAN database to analyze the expression of PXN in AML patients and its prognostic significance. Bone marrow samples of newly diagnosed AML patients were collected to extract RNA, and qRT-PCR was used to detect the expression of PXN . The prognosis was followed up. Chi-square test was used to analyze the relationship between PXN expression and clinical laboratory characteristics. Kaplan-Meier analysis was used to draw survival curve, and Cox regression analysis was used to analyze the independent factors affecting the prognosis of patients with AML. The co-expression genes of PXN were analyzed by LinkedOmics to explore its biological significance in AML. Results: Kaplan-Meier analysis showed that the overall survival time of AML patients was related to whether to receive treatment and PXN expression(P<0.05). COX regression analysis showed that whether to receive treatment (HR=0.227,95%CI=0.075-0.689, P =0.009) and high expression of PXN (HR=4.484,95%CI=1.449-13.889, P =0.009) were independent poor prognostic factors in patients with AML. Conclusion: PXN is highly expressed in AML patient, and high PXN expression is an indicator of poor prognosis in AML patient.


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