TIGIT ligands CD155, CD112, and galectin-9 are associated with immune infiltration and increased overall survival in ovarian cancer

2018 ◽  
Vol 149 ◽  
pp. 56
Author(s):  
K. Starbuck ◽  
K. Morrell ◽  
K. Odunsi ◽  
E. Zsiros ◽  
J.B. Szender ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Mali Chen ◽  
Lili Zhang ◽  
Xiaolong Liu ◽  
Zhen Ma ◽  
Ling Lv

Background: Period circadian protein homolog 1 (PER1) is an important component of the biorhythm molecular oscillation system and plays an important part in the development and progression of mammalian cancer. However, the correlations of PER1 with prognosis and tumor-infiltrating lymphocytes in ovarian cancer (OV) remain unclear.Methods: The Oncomine and TIMER databases were used to examine the expression of PER1 in OV. Kaplan–Meier Plotter and PrognoScan were used to evaluate the relationship between PER1 and prognosis. Kaplan–Meier Plotter was used to analyze the relationships between PER1 and clinicopathological features of OV patients. The relationship between PER1 expression and immune infiltration in OV was investigated using the TIMER database and CIBERSORT algorithm. The STRING database was used to analyze PER1-related protein functional groups, the GeneMANIA online tool was used to analyze gene groups with similar functions to those of PER1, and Network Analyst was used to identify transcription factors that regulate PER1. The correlation between PER1 and immunoinvasion of OV was analyzed using TIMER. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect PER1 expression.Results: PER1 was differentially expressed in different cancer tissues, and its expression in various OV subtypes was lower than that in normal ovarian tissue. OV patients with low PER1 expression had a reduced overall survival rate. Decreased PER1 expression in stage 1 and stage 1+2 OV patients was related to poor prognosis, while increased PER1 expression in stage 3+4 patients and TP53 mutation were related to poor overall survival and progression-free survival. We identified eight genes whose expression was strongly correlated with that of PER1, as well as four transcription factors that regulate PER1. In OV, PER1 expression levels were positively correlated with infiltration levels of cells including neutrophils, regulatory T cells, and M2 macrophages, and closely related to a variety of immune markers. Reduced expression of PER1 was significantly associated with poor overall survival.Conclusion: These findings suggest that PER1 could be used as a prognostic biomarker to determine prognosis and immune infiltration in OV patients.


2021 ◽  
Author(s):  
Jinling Zhang ◽  
Yifan Zhang ◽  
Lin Zhang ◽  
Haili Li

Abstract Background: Dysregulation of metabolism plays a critical role in the pathogenesis and progression of ovarian cancer (OC). However, the expression pattern of metabolic genes in OC and the prognostic value of metabolism-related genes for OC patients remains to be elucidated. Thus, this study aimed to identify a metabolism-related prognostic gene signature for OC. Methods: The expression profiles of metabolism-related genes and associated clinicopathological characteristics were obtained from online datasets (The Cancer Genome Atlas, TCGA and The Genotype-Tissue Expression, GTEx). The differently expressed genes were subjected to functional enrichment analysis. By means of LASSO, univariate and multivariate Cox regression analyses, this predictive signature was constructed and validated by internal and external databases. Genomic alterations, immune infiltration, tumor microenvironment, and drug sensitivity associated with the signature were also described.Results: A total of 302 metabolism-related differentially expressed genes were identified. These genes were mainly enriched in functions associated with substance and energy metabolism. Based on the 302 identified genes, a prognostic signature of 21 metabolic genes was constructed and validated across internal and external cohorts. The patients in the high-risk group had significantly longer overall survival compared to those in the low-risk group. By univariate and multivariate Cox regression, the signature was identified as an independent prognostic predictor for overall survival. There were also noticeable differences with regards to genetic alteration, immune infiltration, tumor microenvironment and drug sensitivity between the two groups.Conclusion: Our study suggests that clinical outcomes of OC patients are associated with dysregulated metabolic genes and that the metabolism-related prognostic signature can be used as a predictor for the overall survival of OC patients.


2021 ◽  
Author(s):  
Jiatao Hao ◽  
Yumeng Cao ◽  
Xiaoya Gu ◽  
Minghai Ma ◽  
Weihong Wang ◽  
...  

Abstract Background SPOCK2 is a member of the SPOCK family, a 424-amino acid protein that binds to glycosaminoglycans to form proteoglycans. The purpose of this study was to explore expression profile of SPOCK2, and evaluate prognostic potential and its correlation with immune infiltration in high-grade serous ovarian cancer (HGSOC). Methods Expression of SPOCK2 mRNA and protein between normal and tumor tissues were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases. Receiver operating characteristic (ROC) curve was used to evaluate diagnostic performance of SPOCK2. Kaplan-Meier method and Cox regression analysis were conducted to assess the effect of SPOCK2 on survival. Nomogram was used to predict the impact of SPOCK2 on prognosis. LinkedOmics were used to find correlated genes and perform functional enrichment analyses. The relationships between SPOCK2 and tumor infiltrating lymphocytes (TILs) were determined by tumor-immune system interaction database (TISIDB) and GSVA package (V1.34.0). Results SPOCK2 was highly expressed in HGSOC tissue compared to normal tissue at both mRNA (P < 0.001) and protein (P = 0.03) levels. The area under the curve (AUC) is 0.894 (CI: 0.865–0.923). Kaplan-Meier analysis showed that HGSOC patients with high-level SPOCK2 mRNA expression had a worse overall survival (OS) than those with a low expression (HR = 1.45, P = 0.005). Univariate logistic regression analysis found that age, primary therapy outcome, tumor status, tumor residual, and SPOCK2 expression level were significantly associated with OS (P < 0.05). The nomogram model indicated an effective predictive performance of SPOCK2. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) term analyses showed that SPOCK2 were mainly involved in regulating extracellular matrix. Immune infiltration analysis showed that SPOCK2 may correlate with abundance of TILs. Conclusion SPOCK2 has potentials to estimate diagnosis and prognosis for HGSOC and is involved in regulating extracellular matrix and immune cell infiltration.


2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rafaela Pirolli ◽  
Viviane Teixeira Loiola de Alencar ◽  
Felipe Leonardo Estati ◽  
Adriana Regina Gonçalves Ribeiro ◽  
Daniella Yumi Tsuji Honda ◽  
...  

Abstract Background Benefit of carboplatin and dose-dense weekly paclitaxel (ddCT) in first line treatment of ovarian cancer patients has been different in Western and Asian studies. In the present study we compare progression-free survival (PFS) of ddCT to three-weekly carboplatin and paclitaxel (CT) in first-line treatment of ovarian carcinoma in a single institution in a Western population. Materials and methods We conducted a retrospective review of medical records from patients with ovarian carcinoma treated in a tertiary cancer center from 2007 to 2018. All patients treated with ddCT or CT in the first-line setting were included. Patients who received first-line bevacizumab were not included. PFS and overall survival (OS) were compared in a propensity score-matched cohort to address selection bias. Patients were matched according to age, ECOG performance status, CA 125, FIGO stage, residual disease, and histological subtype, in a 1:2 ratio. Results Five hundred eighty-eight patients were eligible for propensity score matching, the final cohort consisted of 69 patients treated with ddCT and 138 CT group. Baseline characteristics were well-balanced. After a median follow-up of 65.1 months, median PFS was 29.3 vs 20.0 months, favouring ddCT treatment (p = 0.035). In the multivariate cox regression ddCT showed a 18% lower risk of progression (HR 0.82, 95% CI 0.68–0.99, p = 0.04). Overall survival data is immature, but suggested better outcomes for ddCT (not reached versus 78.8 months; p = 0.07). Conclusion Our retrospective study has shown superior PFS of ddCT over CT regimen in first-line treatment of ovarian carcinoma in a Western population not treated with bevacizumab.


Sign in / Sign up

Export Citation Format

Share Document