scholarly journals An integrated approach for identifying genes associated with chemotherapy resistance in high-grade serous epithelial ovarian cancer

2017 ◽  
Vol 3 (1) ◽  
pp. 31
Author(s):  
Ahmed Hossain ◽  
Gias Uddin Ahsan ◽  
Hayatun Nabi

<p>Treatment with chemotherapy is important in limiting the intensity of serous epithelial ovarian cancer. However, not all patients are sensitive to platinum chemotherapy corresponding to longer progression-free survival (PFS &gt;8 months). Koti <em>et al.</em>[1] revealed a set of 204 discriminating genes possessing expression levels, which could influence differential chemotherapy response between the platinum-resistant and platinum-sensitive group of patients. They considered Welch two-sample <em>t</em>-test and non-parametric Mann-Whitney U test to identify the differentially expressed genes. However, both the statistical methods turned out to be unsuitable for microarray data. In this paper, we used three alternative statistical methods to select a combined list of genes and compared the genes that were proposed by Koti <em>et al.</em>[1]. Subsequently, we recommended using sparse principal component analysis (sparse PCA) to identify a final list of genes. Sparse PCA incorporates correlation into account among the genes and helps to draw a biologically important gene discovery. We identified 77 differentially expressed genes, which include 11 new genes that can separate the groups of patients who are platinum-resistant and platinum-sensitive to the chemotherapy. The integrative approach can also be effective in another high dimensional dataset to compare between two groups.</p>

2020 ◽  
Author(s):  
Yan Rong ◽  
Li Li

Abstract Objectives: To assess the clinical value of early clearance of HE4 and CA125 for platinum sensitivity and prognosis in patients with ovarian cancer.Method: HE4 and CA125 value including clinical data of 89 patients with ovarian cancer were collected. The clearance of HE4 and CA125 were assessed base on the platinum sensitivity, two-year PFS, PFS and OS.Results: 16 patients were classified as platinum resistant and 73 as platinum sensitive according to the response to platinum-base chemotherapy. When HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle chemotherapy, it gave the highest AUC of 0.788, with 100% of sensitivity and 57.5% of specificity respectively between platinum resistant and platinum sensitive group. In addition, 59 patients were classified as two-year PFS group and 30 as not achieved two-year PFS group according to obtaining two-year PFS or not. It gave the highest AUC of 0.730, with 83.3% of sensitivity and 62.7% of specificity respectively when HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle. The prolonged PFS and OS were significantly associated by the clearance of HE4 after 3rd cycle chemotherapy (p<0.0001, p<0.0001) as well as CA125 after 1st cycle chemotherapy (p<0.0001, p<0.0001).Conclusions: Our data suggested that the early clearance of HE4 and CA125 could predict platinum response and prognosis in patients with ovarian cancer. Monitoring the HE4 and CA125 during first-line chemotherapy might be helpful in predicting platinum sensitivity and risk to progress and relapse.


2013 ◽  
Vol 09 (02) ◽  
pp. 129
Author(s):  
Maurie Markman ◽  

Preclinical investigations have provided strong support for the hypothesis that angiogenesis is a potent driver of epithelial ovarian cancer progression. Phase II data have revealed the activity of single-agent bevacizumab in previously treated and clinically defined platinum-resistant ovarian cancer. Several reported phase III randomized trials, involving primary and both ‘platinum-sensitive’ recurrent and platinum-resistant disease, have demonstrated the addition of bevacizumab to a cytotoxic chemotherapy regimen improves progression-free survival compared with chemotherapy alone. While there continues to be considerable debate regarding the optimal dose, timing, and duration of bevacizumab administration in ovarian cancer, the existing data provide strong support for an important role for this agent in the overall management paradigm for this malignancy.


1994 ◽  
Vol 52 (2) ◽  
pp. 247-252 ◽  
Author(s):  
Samuel C. Mok ◽  
Kwong-Kwok Wong ◽  
Raymond K.W. Chan ◽  
Ching C. Lau ◽  
Sai-Wah Tsao ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenwen Guo ◽  
Xue He ◽  
Jing Ni ◽  
Liya Ma ◽  
Xianzhong Cheng ◽  
...  

This study aims to identify differentially expressed proteins related with platinum sensitivity and to find biomarkers for predicting platinum response and survival outcomes in patients with high-grade serous ovarian cancer (HGSOC). Eligible HGSOC patients were divided into platinum-sensitive and platinum-resistant groups according to platinum-free interval (PFI). Tissue protein lysates from tumor tissues were subjected to an in-solution tryptic digest followed by tandem mass tag (TMT) labeling of the resulting peptides and mass spectrometric analysis. Candidate proteins were identified using differentially expressed protein and gene set enrichment analysis (GSEA) and confirmed by immunohistochemistry (IHC), and their survival relevance was evaluated in The Cancer Genome Atlas (TCGA) ovarian cancer cohort. The results showed that there was a significant difference in the protein expression profiling between the two patient groups. In the GSEA model, a gene set of 239 extracellular matrix (ECM)-related proteins was significantly enriched in the platinum-sensitive group [normalized enrichment score (NES) = 3.82, q &lt; 10−5], and this finding was confirmed in TCGA ovarian cancer cohort. Interestingly, an ECM-related gene expression, serpin family A member 10 (SERPINA10), was identified to be significantly positively correlated with overall survival (OS) and progression-free survival (PFS) in TCGA ovarian cancer cohort (all p &lt; 0.05). IHC results demonstrated that HGSOC patients with high SERPINA10 expression had longer PFI than the patients with low SERPINA10 expression (9 vs. 5 months, p = 0.038), and the SERPINA10 expression had an area under the receiver operating characteristic curve (AUC) value of 0.758 (95% CI = 0.612–0.905; p = 0.005) to discriminate the platinum-sensitive group from the platinum-resistant group. In conclusion, the results suggested that SERPINA10 could be a promising biomarker for predicting the response and survival in platinum-based chemotherapy of HGSOC.


2020 ◽  
Author(s):  
Yan Rong ◽  
Li Li

Abstract Objectives: To assess the clinical value of early clearance of HE4 and CA125 for platinum sensitive and prognosis in patients with ovarian cancerMethod: HE4 and CA125 value including clinical data of 89 patients with ovarian cancer were collected. The clearance of HE4 and CA125 were assessed base on the platinum sensitivity, two-year PFS, PFS and OS.Results: 16 patients were classified as platinum resistant and 73 as platinum sensitive according to the response to platinum-base chemotherapy. when HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle chemotherapy, it gave the highest AUC of 0.788, with 100% of sensitivity and 57.5% of specificity respectively between platinum resistant and platinum sensitive group. In addition, 59 patients were classified as two-year PFS group and 30 as not achieved two-year PFS group according to obtaining two-year PFS or not. It gave the highest AUC of 0.730, with 83.3% of sensitivity and 62.7% of specificity respectively when HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle. The prolonged PFS and OS were significantly associated by the clearance of HE4 after 3rd cycle chemotherapy (p < 0.0001, p < 0.0001) as well as CA125 after 1st cycle chemotherapy (p < 0.0001, p < 0.0001).Conclusions: Our data suggest that the early clearance of HE4 and CA125 could predict platinum response and prognosis in patients with ovarian cancer. Monitoring the HE4 and CA125 during first-line chemotherapy might be helpful in predicting platinum sensitive and risk to progress and relapse.


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