scholarly journals Comparative Proteomic Analysis of Advanced Ovarian Cancer Tissue to Identify Potential Biomarkers of Responders and Nonresponders to First-Line Chemotherapy of Carboplatin and Paclitaxel

2016 ◽  
Vol 8 ◽  
pp. BIC.S35775 ◽  
Author(s):  
Urmila Sehrawat ◽  
Ruchika Pokhriyal ◽  
Ashish Kumar Gupta ◽  
Roopa Hariprasad ◽  
Mohd Imran Khan ◽  
...  

Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-β are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response.

2021 ◽  
Vol 27 ◽  
Author(s):  
Wenbin Shen ◽  
Boer Shan ◽  
Shanhui Liang ◽  
Junling Zhang ◽  
Yangyang Yu ◽  
...  

Objective: We conducted this study to characterize somatic genomic alterations in circulating tumor DNA (ctDNA) from patients with ovarian cancer and compare GAs detected in ctDNA with tissue databases.Methods: Hybrid capture-next generation sequencing genomic profiling of 150 genes was performed on ctDNA from 138 patients with ovarian cancer with 1,500× sequencing depth. The GAs detected in ctDNA were compared with those in our ovarian cancer tissue database (N = 488) and the Cancer Genome Atlas (TCGA) database (N = 489).Results: 115 patients (83%) had at least 1 GA detected in ctDNA. The most frequently altered genes detected in ctDNA were TP53 (72%), KRAS (11%), LRP1B (10%), ZNF703 (9%) and NF1 (8%). Comparative analysis with our tissue database showed similar frequencies of GAs per gene, although PIK3CA and KRAS mutations were more frequent in tissue and ctDNA, respectively (p < 0.05). Gene amplification and rearrangement were more frequent in ctDNA samples. The mutation frequency of homologous recombination repair associated-genes, VEGF signal/angiogenesis pathways, RAS pathways, NOTCH pathways and MSI-H ratio was not statistically different either in ctDNA or in tissue database. However, the mutation frequency of AKT, PIK3CA, PTEN and STK11 in PI3K/AKT/mTOR pathway was significantly lower than that in tissue samples (p < 0.05).Conclusions: Our results suggest that genomic profiling of ctDNA could detect somatic GAs in a significant subset of patients with ovarian cancer. Hybrid capture-NGS based on liquid biopsy has the potential capability to serve as a substitute to tissue biopsy and further studies are warranted.


2016 ◽  
Vol 15 ◽  
pp. CIN.S40660 ◽  
Author(s):  
Alexandros Laios ◽  
Davide Volpi ◽  
Rajeev Kumar ◽  
Zoe Traill ◽  
Borivoj Vojnovic ◽  
...  

In patients with advanced ovarian cancer (AOC), additional imaging of disseminated disease at laparoscopy could complement conventional imaging for estimation of chemotherapy response. We developed an image segmentation method and evaluated its use in making accurate and objective measurements of peritoneal metastases in comparison to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. A software tool using a custom ImageJ macro-based approach was employed to estimate lesion size by converting image pixels into unit length. The software tool was tested as a proof-of-principle in an AOC patient with two isolated peritoneal deposits. Image analysis of representative laparoscopic snapshots before and after three cycles of neoadjuvant chemotherapy (NACT) revealed an average tumor nodule response ratio (TNRR) of 40% (partial response), which was in concordance with RECIST evaluation by computed tomography (CT). We demonstrated the feasibility of using this novel anatomical analysis for direct assessment of chemotherapy response in an AOC patient as an adjunct to RECIST criteria.


2019 ◽  
Vol 11 ◽  
pp. 1179299X1986081 ◽  
Author(s):  
Ruchika Pokhriyal ◽  
Roopa Hariprasad ◽  
Lalit Kumar ◽  
Gururao Hariprasad

Ovarian cancer is the seventh most common gynaecologic malignancy seen in women. Majority of the patients with ovarian cancer are diagnosed at the advanced stage making prognosis poor. The standard management of advanced ovarian cancer includes tumour debulking surgery followed by chemotherapy. Various types of chemotherapeutic regimens have been used to treat advanced ovarian cancer, but the most promising and the currently used standard first-line treatment is carboplatin and paclitaxel. Despite improved clinical response and survival to this combination of chemotherapy, numerous patients either undergo relapse or succumb to the disease as a result of chemotherapy resistance. To understand this phenomenon at a cellular level, various macromolecules such as DNA, messenger RNA and proteins have been developed as biomarkers for chemotherapy response. This review comprehensively summarizes the problem that pertains to chemotherapy resistance in advanced ovarian cancer and provides a good overview of the various biomarkers that have been developed in this field.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15531-e15531
Author(s):  
Hannah Woopen ◽  
Klaus Pietzner ◽  
Rolf Richter ◽  
Christina Fotopoulou ◽  
Thomas Joens ◽  
...  

e15531 Background: EpCAM, a well known cancer antigene is currently experiencing a renaissance in its use as a binding site for targeted oncologic therapy and prognostic marker in various epithelial carcinomas such as breast cancer or carcinomas of the oral cavity. Goal of this retrospective study was to identify EpCAM as a potential prognostic marker for patients with primary epithelial ovarian cancer (EOC). Methods: EpCAM expression was assessed in tumor tissue by immunohistochemistry using the Avidin-Biotin-Complex method on paraffin-embedded ovarian cancer tissue samples. EpCAM overexpression was defined as an expression of EpCAM as high as 76-100%. Clinical data as well as tumor tissue samples were collected within the validated “Tumor bank Ovarian Cancer Network (TOC)”. Results: Seventy-four patients with the primary diagnosis of EOC between 01/1994 and 12/2009 were included in this study. Median age at diagnosis was 56 years. The vast majority of the patients (75.4%) presented an advanced stage disease (FIGO III/IV). Forty-one (55.4%) patients were diagnosed with a serous, 19 (25.6%) a endometrioid and 14 (19%) a mucinous histology. EpCAM was overexpressed in 87.7% of the patients. Serous tumors expressed EpCAM in significantly higher rates than mucinous tumors ( p=0.045). EpCAM overexpression correlated in univariate analysis with a significantly better overall survival. Multivariate analysis including histological subtype identified EpCAM expression of 76-100% to be independently associated with a significantly better overall survival compared to a lower EpCAM expression of ≤50% (p=0.008). Conclusions: EpCAM overexpression in EOC appears to be associated with significantly higher overall survival rates. Larger, prospectively assessed multicenter studies are warranted to further evaluate and confirm these novel findings and possibly establish EpCAM as a potent therapeutic target in EOC.


1989 ◽  
Vol 185 (5) ◽  
pp. 676-679 ◽  
Author(s):  
A.-R. Weger ◽  
Chr. Ludescher ◽  
G. Mikuz ◽  
G. Kemmler ◽  
R. Reitsamer ◽  
...  

2014 ◽  
Vol 28 (2) ◽  
pp. 273-281 ◽  
Author(s):  
Arkadiusz Gajek ◽  
Marta Denel ◽  
Barbara Bukowska ◽  
Aneta Rogalska ◽  
Agnieszka Marczak

2017 ◽  
Vol 46 (2) ◽  
pp. 723-731 ◽  
Author(s):  
Cai-xia Zhu ◽  
Wei Xiong ◽  
Ma-lie Wang ◽  
Juan Yang ◽  
Hui-juan Shi ◽  
...  

Objective To demonstrate the correlation between nuclear and cytoplasmic G protein-coupled oestrogen receptor (GPR30) expression and clinicopathological features and outcome in patients with ovarian cancer. Methods Nuclear and cytoplasmic GPR30 expressions were determined using immunohistochemistry to identify the intracellular location in tissues from patients with ovarian cancer. Data were correlated with clinicopathological characteristics and outcomes. Results Tissue samples were obtained from 110 patients with epithelial ovarian cancer between 2005 and 2010. Nuclear GPR30 was significantly more frequent in the group of patients with recurrence. The presence of nuclear GPR30 predicted lower overall survival) and 5-year progression-free survival in all patients with ovarian cancer and overall survival in patients with high grade ovarian cancer. Cytoplasmic GPR30 was observed significantly more often in advanced ovarian cancer and did not predict survival. Conclusion This study showed that nuclear GPR30 is an independent negative prognostic indicator in patients with ovarian cancer, especially in those with a high grade malignancy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yunlong Cui ◽  
Hua Li ◽  
Hongjie Zhan ◽  
Tao Han ◽  
Yixuan Dong ◽  
...  

Liver cancer is a common malignant tumor worldwide, which is a serious threat to the health of people. We try to investigate some mutations and clinical indicators as candidate markers for the development of liver cancer through targeted region capture technology combined with next-generation sequencing. We collected peripheral blood and liver cancer tissue samples from 32 liver patients concurrently. The SeqCap EZ Prime Choice Probe was used to perform the targeted enrichment; this probe captures 1,000 known cancer-associated genes. We calculated the tumor mutation burden (TMB) for each patient. The high-frequency mutations and these relative genes were identified. Eventually, survival analysis was performed based on the mutations and clinical indicators. In 32 liver patients, a total of 29 high-frequency mutations were investigated. They were located in 25 genes, which were enriched in 9 cellular components (CCs), 6 molecular functions (MFs), and 21 biological processes (BPs). Among them, EZH2 c.1544A>G and CCND1 c.839A>T had the highest mutation frequency (5/32). In the protein–protein interaction (PPI) network, EZH2-DNMT3A, NOTCH1-CCND1, and ABL1-CCND1 were the top three pairs. The survival analysis showed that there were significant differences in progression-free survival (PFS) and overall survival (OS) between the Karnofsky performance score (KPS) groups. The PFS and OS in the TMB high group were higher than those in the TMB low group. OS and tumor stage had a remarkable relationship. In conclusion, EZH2 c.1544A>G and CCND1 c.839A>T might be potential biomarkers of liver cancer. TMB might be used as a prognosis and survival indicator of liver cancer.


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