scholarly journals Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 149 ◽  
Author(s):  
Katarzyna Aleksandra Kujawa ◽  
Ewa Zembala-Nożyńska ◽  
Alexander Jorge Cortez ◽  
Tomasz Kujawa ◽  
Jolanta Kupryjańczyk ◽  
...  

Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan–Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan–Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02–4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian–epithelial origin of the tumor.


2019 ◽  
Vol 8 (10) ◽  
pp. 1647 ◽  
Author(s):  
Sachiyo Onishi ◽  
Masahiro Tajika ◽  
Tsutomu Tanaka ◽  
Yutaka Hirayama ◽  
Kazuo Hara ◽  
...  

The prognostic significance of sarcopenia in unresectable advanced esophageal cancer remains unclear. Our study retrospectively evaluated 176 consecutive Japanese patients with esophageal squamous cell carcinoma who had been diagnosed with unresectable advanced cancer in Aichi Cancer Center Hospital between January 2007 and December 2014. Skeletal muscle mass was calculated from abdominal computed tomography (CT) scans before treatment, and patients were divided into sarcopenic and non-sarcopenic groups. Sarcopenia was present in 101 patients (57.4%). Eighty-two patients in the sarcopenic group and 63 patients in the non-sarcopenic group died during follow-up (mean: 20.3 months). The overall survival (OS) rate was significantly lower in the sarcopenic group compared to the non-sarcopenic group (2-year OS: 9.8% vs. 23.7%, p < 0.01). Cox regression analysis revealed only pretreatment sarcopenia as an independent prognostic factor (hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.04–2.10, p = 0.03). In the sarcopenic group, withdrawn cases, for whom the planned treatment was discontinued for some reason, showed a significantly lower OS rate compared to complete cases (1-year OS: 11.0% vs. 59.9%, p < 0.01). The most common reason for discontinuation was aspiration pneumonia (64.5%). Presence of sarcopenia was an independent prognostic factor for unresectable advanced esophageal cancer. Identifying the presence of sarcopenia prior to treatment may improve the prognosis.



Author(s):  
Dan Chang ◽  
Yichun Cheng ◽  
Ran Luo ◽  
Chunxiu Zhang ◽  
Meiying Zuo ◽  
...  

Abstract Purpose Platelet-to-lymphocyte ratio (PLR) was established showing the poor prognosis in several diseases, such as malignancies and cardiovascular diseases. But limited study has been conducted about the prognostic value of PLR on the long-term renal survival of patients with Immunoglobulin A nephropathy (IgAN). Methods We performed an observational cohort study enrolling patients with biopsy-proven IgAN recorded from November 2011 to March 2016. The definition of composite endpoint was eGFR decrease by 50%, eGFR < 15 mL/min/1.73 m2, initiation of dialysis, or renal transplantation. Patients were categorized by the magnitude of PLR tertiles into three groups. The Kaplan–Meier curves and multivariate Cox models were performed to determine the association of PLR with the renal survival of IgAN patients. Results 330 patients with a median age of 34.0 years were followed for a median of 47.4 months, and 27 patients (8.2%) had reached the composite endpoints. There were no differences among the three groups (PLR < 106, 106 ≤ PLR ≤ 137, and PLR > 137) in demographic characteristics, mean arterial pressure (MAP), proteinuria, and estimated glomerular filtration rate (eGFR) at baseline. The Kaplan–Meier curves showed that the PLR > 137 group was significantly more likely to poor renal outcomes than the other two groups. Using univariate and multivariate cox regression analyses, we found that PLR > 137 was an independent prognostic factor for poor renal survival in patients with IgAN. Subgroup analysis revealed that the PLR remained the prognostic value for female patients or patients with eGFR less than 60 mL/min/1.73 m2. Conclusions Our results underscored that baseline PLR was an independent prognostic factor for poor renal survival in patients with IgAN, especially for female patients or those patients with baseline eGFR less than 60 mL/min/1.73 m2.



2021 ◽  
pp. 1-8
Author(s):  
Fatma Bugdayci Basal ◽  
Cengiz Karacin ◽  
Irem Bilgetekin ◽  
Omur Berna Oksuzoglu

Introduction: The aim of the study was to evaluate impact of the systemic immune-inflammation index (SII) on prognosis and survival within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score groups. Methods: The records of 187 patients with metastatic renal cell carcinoma (RCC) were reviewed retrospectively. The SII was calculated as follows: SII = Neutrophil × Platelet/Lymphocyte. The patients were categorized into 2 groups based on a median SII of 730 (×109 per 1 L) as SII low (<730) and SII high (≥730). The Kaplan-Meier method was used for survival analysis and a Cox regression model was utilized to determine independent predictors of survival. Results: The median age was 61 years (range: 34–86 years). Kaplan-Meier tests revealed significant differences in survival between the SII-low and SII-high levels (27.0 vs. 12.0 months, respectively, p < 0.001). The Cox regression model revealed that SII was an independent prognostic factor. The implementation of the log-rank test in the IMDC groups according to the SII level provided the distinction of survival in the favorable group (SII low 49.0 months vs. SII high 11.0 months, p < 0.001), in the intermediate group (SII low 26.0 vs. SII high 15.0 months, p = 0.007), and in the poor group (SII low 19.0 vs. SII high 6.0 months, p = 0.019). Conclusion: The SII was an independent prognostic factor and provided significant differences in survival for the favorable, intermediate, and poor IMDC groups. Thus, the SII added to the IMDC score may be clinically beneficial in predicting survival.





2006 ◽  
Vol 24 (5) ◽  
pp. 755-761 ◽  
Author(s):  
Liz Y. Han ◽  
Charles N. Landen ◽  
Aparna A. Kamat ◽  
Adriana Lopez ◽  
David P. Bender ◽  
...  

Purpose Tissue factor (TF) is a procoagulant that plays an important part in tumor angiogenesis. We sought to determine the role of preoperative serum TF levels in predicting clinical outcome in patients with ovarian cancer. Materials and Methods TF expression was determined by reverse transcriptase polymerase chain reaction in ovarian cell lines. Using enzyme-linked immunosorbent assay, we assessed preoperative serum TF levels in 98 women with invasive epithelial ovarian carcinoma, 30 with low malignant potential (LMP) tumors, 16 with benign tumors, and a separate validation group of 39 women with adnexal masses. Clinical information was gathered from chart review. Results TF was expressed in four of the five ovarian cancer cell lines, but absent in the nontransformed cells. Ovarian cancer patients had a median preoperative serum TF level of 85.2 pg/mL, which was significantly higher than in those with LMP tumors (12.8 pg/mL; P < .01) and benign adnexal disease (30.7 pg/mL; P < .01). TF ≥ 190 pg/mL was significantly associated with decreased patient survival (P < .01). After adjusting for other clinical variables in a multivariate Cox regression model, TF ≥ 190 pg/mL was an independent prognostic factor (P < .01). Analysis of serum TF levels from the validation set confirmed that high TF (≥190 pg/mL) was associated with a 3.4-fold increase in risk of death from disease (P = .02) and shorter survival (P = .01). Conclusion Preoperative serum TF levels are significantly elevated in patients with ovarian carcinoma. Elevated preoperative TF level is an independent prognostic factor for death from disease.



Author(s):  
Michael Stotz ◽  
Joanna Szkandera ◽  
Tatjana Stojakovic ◽  
Julia Seidel ◽  
Hellmut Samonigg ◽  
...  

AbstractIntra-tumoral macrophages have been involved as important players in the pathogenesis and progression of cancer. Recently, inflammatory parameters of the systemic inflammatory response have also been proposed as usefully prognostic biomarkers. One of these, the lymphocyte to monocyte ratio (LMR) in peripheral blood has been shown as a prognostic factor in hematologic and some solid tumors. In this study we analyzed for the first time the prognostic value of LMR in a large middle European cohort of pancreatic cancer (PC) patients.Data from 474 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Cancer-specific survival (CSS) was analyzed using the Kaplan-Meier method. To further evaluate the prognostic significance of the LMR, univariate and multivariate Cox regression models were calculated.Increased LMR at diagnosis was significantly associated with well-established prognostic factors, including high tumor stage and tumor grade (p<0.05). In univariate analysis, we observed that an increased LMR was a significant factor for better CSS in PC patients (HR 0.70; 95% CI 0.57–0.85; p<0.001). In multivariate analysis including age, Karnofsky Index, tumor grade, tumor stage, administration of chemotherapy, LMR and surgical resection, we confirmed increased LMR as an independent prognostic factor for CSS (HR 0.81; 95% CI 0.66–0.99; p=0.04).In conclusion, we identified LMR as an independent prognostic factor in PC patients. Our results indicate that the LMR might represent a novel and useful marker for patient stratification in PC management.



2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Changhua Zhuo ◽  
Xianyi Wu ◽  
Jing Li ◽  
Dan Hu ◽  
Jinliang Jian ◽  
...  

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemotactic cytokine known to regulate cancer progression and invasion. However, the prognostic significance of CXCL1 expression in colorectal cancer (CRC) has not been fully characterized. The present study explored the clinicopathological significance and potential role of CXCL1 in the carcinogenesis and progression of CRC. The protein expression of CXCL1 was measured immunohistochemically in tissue microarrays constructed from 276 CRC patients. CXCL1 expression levels and their associations with clinicopathological characteristics and patient survival were evaluated. The effect of CXCL1 on glycolysis was also examined. High CXCL1 expression was detected in 165 (59.8%) cases. CXCL1 expression was correlated with tumor diameter (P=0.002), T stage (P=0.044), N stage (P=0.005), M stage (P=0.001), lymphovascular invasion (P=0.010), and carcinoembryonic antigen status (P=0.019). High CXCL1 expression was validated as an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) by both univariate and multivariate Cox regression analyses (both P<0.05). Experimentally, expression of CXCL1 was knocked down by stable transfected short hairpin RNA, resulting in a significantly decreased rate of glycolysis both in in vitro assays and in patients’ samples (P<0.05). Silencing the expression of CXCL1 decreased the levels of the glycolytic enzymes GLUT1, HK2, and LDHA. In conclusion, by inducing glycolysis, CXCL1 plays a crucial role in both cancer progression and metastasis in CRC patients. The CXCL1 expression level is an independent prognostic factor for both OS and DFS. Moreover, CXCL1 may serve as a new biomarker and potential therapeutic target for CRC treatment.



2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16522-e16522
Author(s):  
Fruzsina Gyergyay ◽  
Barna Budai ◽  
Krisztina Biro ◽  
Zsofia Kuronya ◽  
Krisztian Nagyivanyi ◽  
...  

e16522 Background: Cs are commonly used in the treatment of mCRPC, because of their inhibitory effects on the secretion of ACTH and their palliative effects. Inhibition of ACTH results in downregulation of adrenal androgens. Cs may have a cytotoxic effect on prostate cancer cells, mediated in part by the downregulation of androgen receptors and the activation of glucocorticoid receptor-mediated signaling and downstream antiangiogenic activity. The rationale for adding Cs to D chemotherapy is for the management of symptoms and adverse events rather than for improving responses. D (without Cs) + ADT (androgen-deprivation therapy) vs ADT alone in castration-sensitive prostate cancer has resulted in significant increase in survival (NEJM, 2015). Cs has been reported to adversely influence OS during enzalutamide (NEJM, 2012). In the COU-AA-301 trial Cs use at baseline was an independent prognostic factor in multivariate analysis, but not in a stepwise selection model (JCO, 2013). Methods: We performed a retrospective analysis of 117 mCRPC pts treated with D. All pts had standard Cs premedication before D and 74 pts received prednisone 5 mg po BID, but 43 pts didn’t get continuous Cs therapy. Kaplan-Meier estimates and Cox regression model were used. Results: Pts characteristics were as follows: median age 66 yrs (range 48-81), Gleason score ≤6: 22pts, ≥7: 61pts. (34 NA). Altogether 1015 cycles of D were given, median 8 (range 2-27). Subsequent therapies were as follows: Abiraterone Acetate (AA) (75), Mitoxantrone (46), Xofigo (5), other chemotherapies (7), none (21). Pts receiving Cs had an inferior OS in all subgroups, although none was significant (Table). Only the Gleason score was an independent prognostic factor in multivariate analysis. Conclusions: Our data suggest, that D therapy withouth Cs is at least as effective as the combination. More data is neccesary to support the suspicion of negative influence of Cs on OS. Thus unnecesarry Cs treatment might be ommited. [Table: see text]



Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 973
Author(s):  
Olivia Knittelfelder ◽  
Daniela Delago ◽  
Gabi Jakse ◽  
Sabine Reinisch ◽  
Richard Partl ◽  
...  

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000–2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38–2.12; p < 0.001) and OS (HR 1.69, 95% CI 1.41–2.02; p < 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12–1.88, p = 0.005 and HR 1.42, 95% CI 1.14–1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio > 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10–2.43, p = 0.014 and HR 1.55, 95% CI 1.12–2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions.



2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kai Li ◽  
Guang Wu ◽  
Caibin Fan ◽  
Hexing Yuan

Abstract Background To evaluate the association of primary tumor size with clinicopathologic characteristics and survival of patients with squamous cell carcinoma of the penis (SCCP). Methods This study analyzed the data of 1001 patients with SCCP, obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. The Kaplan–Meier method and the Cox proportional hazards regression model were used to analyze the effects of primary tumor size on overall survival (OS) and penile carcinoma-specific survival (PCSS). Results Advanced T stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P = 0.001) were more frequently associated with SCCP patients with tumor size ≥ 3 cm than those with tumor size  < 3 cm. In Kaplan–Meier analyses, the patients with large tumors (≥ 3 cm) exhibited an inferior OS and PCSS than those with small tumors (< 3 cm). Moreover, tumor size was identified to be an independent prognostic factor for OS [hazard ratio (HR) 1.665, P < 0.001] and PCSS (HR 2.076, P = 0.003) of patients with SCCP in multivariate analyses. Conclusions Large tumor size is associated with adverse clinicopathological characteristics of patients with SCCP. Besides, tumor size represents an independent prognostic factor for OS and PCSS. Therefore, clinical assessment of tumor size as a crucial prognostic factor might be highly beneficial for early intervention in patients with SCCP.



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