scholarly journals Integrin α2β1 Represents a Prognostic and Predictive Biomarker in Primary Ovarian Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 289
Author(s):  
Katharina Dötzer ◽  
Friederike Schlüter ◽  
Franz Edler von Koch ◽  
Christine E. Brambs ◽  
Sabine Anthuber ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Cancer Progression ◽  
Survival Data ◽  
Cox Regression ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
High Recurrence Rate ◽  
Cox Regression Analysis ◽  
Primary Ovarian Cancer

Currently, the same first-line chemotherapy is administered to almost all patients suffering from primary ovarian cancer. The high recurrence rate emphasizes the need for precise drug treatment in primary ovarian cancer. Being crucial in ovarian cancer progression and chemotherapeutic resistance, integrins became promising therapeutic targets. To evaluate its prognostic and predictive value, in the present study, the expression of integrin α2β1 was analyzed immunohistochemically and correlated with the survival data and other therapy-relevant biomarkers. The significant correlation of a high α2β1-expression with the estrogen receptor alpha (ERα; p = 0.035) and epithelial growth factor receptor (EGFR; p = 0.027) was observed. In addition, high α2β1-expression was significantly associated with a low number of tumor-infiltrating immune cells (CD3 intratumoral, p = 0.017; CD3 stromal, p = 0.035; PD-1 intratumoral, p = 0.002; PD-1 stromal, p = 0.049) and the lack of PD-L1 expression (p = 0.005). In Kaplan–Meier survival analysis, patients with a high expression of integrin α2β1 revealed a significant shorter progression-free survival (PFS, p = 0.035) and platinum-free interval (PFI, p = 0.034). In the multivariate Cox regression analysis, integrin α2β1 was confirmed as an independent prognostic factor for both PFS (p = 0.021) and PFI (p = 0.020). Dual expression of integrin α2β1 and the hepatocyte growth factor receptor (HGFR; PFS/PFI, p = 0.004) and CD44v6 (PFS, p = 0.000; PFI, p = 0.001; overall survival [OS], p = 0.025) impaired survival. Integrin α2β1 was established as a prognostic and predictive marker in primary ovarian cancer with the potential to stratify patients for chemotherapy and immunotherapy, and to design new targeted treatment strategies.

scholarly journals Comprehensive pathway-related genes signature for prognosis and recurrence of ovarian cancer

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10437
Author(s):  
Xinnan Zhao ◽  
Miao He
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Time Dependent ◽  
Prognostic Indicators ◽  
High Recurrence Rate ◽  
Cox Regression Analysis ◽  
Ovarian Tumorigenesis

Background Ovarian cancer (OC) is a highly malignant disease with a poor prognosis and high recurrence rate. At present, there is no accurate strategy to predict the prognosis and recurrence of OC. The aim of this study was to identify gene-based signatures to predict OC prognosis and recurrence. Methods mRNA expression profiles and corresponding clinical information regarding OC were collected from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) and LASSO analysis were performed, and Kaplan–Meier curves, time-dependent ROC curves, and nomograms were constructed using R software and GraphPad Prism7. Results We first identified several key signalling pathways that affected ovarian tumorigenesis by GSEA. We then established a nine-gene-based signature for overall survival (OS) and a five-gene-based-signature for relapse-free survival (RFS) using LASSO Cox regression analysis of the TCGA dataset and validated the prognostic value of these signatures in independent GEO datasets. We also confirmed that these signatures were independent risk factors for OS and RFS by multivariate Cox analysis. Time-dependent ROC analysis showed that the AUC values for OS and RFS were 0.640, 0.663, 0.758, and 0.891, and 0.638, 0.722, 0.813, and 0.972 at 1, 3, 5, and 10 years, respectively. The results of the nomogram analysis demonstrated that combining two signatures with the TNM staging system and tumour status yielded better predictive ability. Conclusion In conclusion, the two-gene-based signatures established in this study may serve as novel and independent prognostic indicators for OS and RFS.

scholarly journals Role of a Pyroptosis-Related lncRNA Signature in Risk Stratification and Immunotherapy of Ovarian Cancer

2022 ◽  
Vol 8 ◽  
Author(s):  
Zeyu Zhang ◽  
Zhijie Xu ◽  
Yuanliang Yan
Keyword(s):  
Ovarian Cancer ◽  
Risk Stratification ◽  
Survival Data ◽  
Risk Model ◽  
Cox Regression ◽  
Roc Curves ◽  
Immune Checkpoints ◽  
Random Allocation ◽  
Cox Regression Analysis

Background: Pyroptosis is a newly recognized form of cell death. Emerging evidence has suggested the crucial role of long non-coding RNAs (lncRNAs) in the tumorigenesis and progression of ovarian cancer (OC). However, there is still poor understanding of pyroptosis-related lncRNAs in OC.Methods: The TCGA database was accessed for gene expression and clinical data of 377 patients with OC. Two cohorts for training and validation were established by random allocation. Correlation analysis and Cox regression analysis were performed to identify pyroptosis-related lncRNAs and construct a risk model.Results: Six pyroptosis-related lncRNAs were included in the final signature with unfavorable survival data. Subsequent ROC curves showed promising predictive value of patient prognosis. Further multivariate regression analyses confirmed the signature as an independent risk factor in the training (HR: 2.242, 95% CI: 1.598–3.145) and validation (HR: 1.884, 95% CI: 1.204–2.95) cohorts. A signature-based nomogram was also established with a C-index of.684 (95% CI: 0.662–0.705). Involvement of the identified signature in multiple immune-related pathways was revealed by functional analysis. Moreover, the signature was also associated with higher expression of three immune checkpoints (PD-1, B7-H3, and VSIR), suggesting the potential of the signature as an indicator for OC immunotherapies.Conclusion: This study suggests that the identified pyroptosis-related lncRNA signature and signature-based nomogram may serve as methods for risk stratification of OC. The signature is also associated with the tumor immune microenvironment, potentially providing an indicator for patient selection of immunotherapy in OC.

scholarly journals The Detection of Stem-Like Circulating Tumor Cells Could Increase the Clinical Applicability of Liquid Biopsy in Ovarian Cancer

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 815
Author(s):  
Snezhanna O. Gening ◽  
Tatyana V. Abakumova ◽  
Dina U. Gafurbaeva ◽  
Albert A. Rizvanov ◽  
Inna I. Antoneeva ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Progression ◽  
Cox Regression ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Paired Samples

Stem properties allow circulating tumor cells (CTCs) to survive in the bloodstream and initiate cancer progression. We aimed to assess the numbers of stem-like CTCs in patients with ovarian cancer (OC) before treatment and during first-line chemotherapy (CT). Flow cytometry was performed (Cytoflex S (Beckman Coulter, CA, USA)) using antibodies against CD45; epithelial markers EpCAM and cytokeratin (CK) 8,18; mesenchymal vimentin (vim); and stem-like CD44, CD133 and ALDH. This study included 38 stage I–IV OC patients (median age 66 (Q1–Q3 53–70)). The CK+vim- counts were higher (p = 0.012) and the CD133+ALDHhigh counts were lower (p = 0.010) before treatment in the neoadjuvant CT group than in the adjuvant group. The patients with ascites had more CK+vim- cells before treatment (p = 0.009) and less EpCAM-vim+ cells during treatment (p = 0.018) than the patients without ascites. All the CTC counts did not differ significantly in paired samples. Correlations were found between the CK-vim+ and CD133+ALDHhigh (r = 0.505, p = 0.027) and EpCAM-vim+ and ALDHhigh (r = 0.597, p = 0.004) cells before but not during treatment. Multivariate Cox regression analysis showed that progression-free survival was longer with the presence of surgical treatment (HR 0.06 95% CI 0.01–0.48, p = 0.009) and fewer CD133+ALDHveryhigh cells (HR 1.06 95% CI 1.02–1.12, p = 0.010). Thus, CD133+ALDH+ CTCs have the greatest prognostic potential in OC among the phenotypes studied.

Exploratory evaluation of pharmacodynamic biomarkers and pharmacokinetics (PK) of ziv-aflibercept (Z) + FOLFIRI in a phase II study of Japanese patients (pts) with metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 799-799 ◽  
Author(s):  
Takayuki Yoshino ◽  
Naotoshi Sugimoto ◽  
Kentaro Yamazaki ◽  
Takeshi Kajiwara ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cox Regression ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Tumor Stroma ◽  
Japanese Patients ◽  
Protein Biomarkers ◽  
Cox Regression Analysis ◽  
Pharmacodynamic Biomarkers ◽  
Potential Biomarkers

799 Background: Z + 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) is a 2nd-line treatment for mCRC. There are no established biomarkers that predict response to this treatment. This study aimed to identify such biomarkers. Methods: 62 pts with mCRC received Z (4 mg/kg) + FOLFIRI every 2 weeks. 78 potential protein biomarkers (e.g., cytokines) were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor-stroma interaction. Plasma levels of biomarkers at baseline and pre-dose 3 (Day 1 of Cycle 3) were measured in all pts by enzyme-linked immunosorbent assays. Relationships between these levels and efficacy endpoints were assessed. PK data were calculated. Results: 10 potential biomarkers had a ±30% change from baseline to pre-dose 3 (adjusted P < .001); the greatest changes were in placental growth factor (median: 4,716%) and vascular endothelial growth factor receptor 1 (2,171%). Baseline levels of 8 potential biomarkers correlated with overall survival (OS; see table) in a univariate Cox regression analysis; none correlated with progression-free survival or maximum tumor shrinkage. Pre-dose 3 levels did not correlate with any efficacy endpoints. Conclusions: Preliminary data show that these 8 biomarkers could be associated with OS. No significant drug interactions were found. Clinical trial information: NCT01882868. [Table: see text]

scholarly journals Immunohistochemical evaluation of insulin-like growth factor receptor 1 in breast cancer

2018 ◽  
Vol 146 (9-10) ◽  
pp. 524-529
Author(s):  
Danijela Batinic-Skipina ◽  
Radmil Maric ◽  
Ljiljana Tadic-Latinovic ◽  
Drazan Eric ◽  
Nenad Lalovic
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Growth Factor Receptor ◽  
Disease Stage ◽  
Insulin Like Growth Factor ◽  
Cox Regression Analysis ◽  
Multifocal Breast Cancer ◽  
Her 2

Introduction/Objective. Activation of insulin-like growth factor receptor (IGF-1R) results in cell transition from growth phase to synthesis phase of cell cycle. Breast cancer is categorized into prognostic and therapeutic subtypes based upon hormone receptor, estrogen receptor (ER), and progesterone receptor (PR) expression and human epidermal growth factor receptor 2 (HER-2) expression. The objective of this study was to examine the expression of IGF-1R in ? specific subtype invasive breast cancer and its correlation with basic histopathological and immunohistochemical prognostic parameters. Methods. Formalin-fixed paraffin-embedded tumor samples were obtained from 129 female patients with invasive breast cancer (I?III disease stage) with the follow-up ranging 36?108 months (average 48 months). For immunohistochemical staining, we used monoclonal antibodies for ER, PR, IGF-1R, and polyclonal antibody for HER-2. Results. IGF-1R inversely correlated with tumor stage (p = 0.017), tumor grade (p = 0.001), HER-2 (p = 0.003), whereas significant positive correlation was found with multifocality/multicentricity of breast cancer (p = 0.036), ER (p = 0.001) and PR (p = 0.0001) expression. Cox-regression analysis for relapse-free survival (RFS) showed that disease stage (p = 0.039) and HER-2 (p = 0.033) were independent prognostic factors. IGF-1R did not predict clinical outcome in patients with breast cancer (p = 0.488, Kaplan?Meier test for RFS). Conclusion. Patients with low stage and grade hormone-dependent breast cancer had a significantly higher IGF-1R expression than patients with triple negative or HER-2 overexpressed cancer. The present findings also highlight that IGF-1R expression in multicentric/multifocal breast cancer supports the key roles in tumor initiation.

scholarly journals Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yang You ◽  
Qi Fan ◽  
Jianyun Huang ◽  
Yaoqiu Wu ◽  
Haiyan Lin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cell ◽  
Cancer Progression ◽  
Scoring System ◽  
Tumor Metastasis ◽  
Cox Regression ◽  
Lipid Peroxides ◽  
Consensus Clustering ◽  
Cox Regression Analysis ◽  
Gynecological Malignancy

Ovarian cancer is a kind of gynecological malignancy with high mortality. Ferroptosis is a new type of iron-dependent cell death characterized by the formation of lipid peroxides and excessive accumulation of reactive oxygen species. Studies have shown that ferroptosis modulates tumor genesis, progression, and invasion, including ovarian cancer. Based on the mRNA expression data from TCGA, we construct a scoring system using consensus clustering analysis, univariate Cox regression analysis, and least absolute selection operator. Then, we systematically evaluate the relationship between score and clinical characteristics of ovarian cancer. The result from the prediction of biofunction pathways shows that score serves as an independent prognostic marker for ovarian cancer and affects tumor progression by modulating tumor metastasis. Moreover, immunocytes such as activated CD4 T cell, activated CD8 T cell, regulatory T cells, macrophage, and stromal cells, including adipocytes, epithelial cells, and fibroblast infiltrate more in the tumor microenvironment in a high-score group, indicating ferroptosis can also affect tumor immune landscape. Critically, four potentially sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1 based on the scores, are predicted, and DMOG is recognized as a novel targeted drug for ovarian cancer. In general, we construct the scoring system based on ferroptosis-related genes that can predict the prognosis of ovarian cancer patients and propose that ferroptosis may affect ovarian cancer progression by mediating tumor metastasis and immune landscape. Novel drugs to target ovarian cancer are also predicted.

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