scholarly journals Hepatobiliary Disease Resection in Patients with Advanced Epithelial Ovarian Cancer: Prognostic Role and Optimal Cytoreduction

2020 ◽  
Vol 28 (1) ◽  
pp. 222-230 ◽  
Author(s):  
Violante Di Donato ◽  
Andrea Giannini ◽  
Ottavia D’Oria ◽  
Michele Carlo Schiavi ◽  
Anna Di Pinto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Perioperative Complications ◽  
Prognostic Significance ◽  
Complete Cytoreduction ◽  
Biliary Disease ◽  
Curative Intent ◽  
Perioperative Morbidity ◽  
Kaplan Meier ◽  
Tumor Load ◽  
Multivisceral Surgery

Abstract Objective The purpose of this study was to evaluate the feasibility and safety in terms of prognostic significance and perioperative morbidity and mortality of cytoreduction in patients affected by advance ovarian cancer and hepato-biliary metastasis. Methods Patients with a least one hepatobiliary metastasis who have undergone surgical treatment with curative intent of were considered for the study. Perioperative complications were evaluated and graded with Accordion severity Classification. Five-year PFS and OS were estimated using the Kaplan–Meier curve. Results Sixty-seven (20.9%) patients had at least one metastasis to the liver, biliary tract, or porta hepatis. Forty-four (65.7%) and 23 (34.3%) patients underwent respectively high and intermediate complexity surgery according. Complete cytoreduction was achieved in 48 (71.6%) patients with hepato-biliary disease. In two patients (2.9%) severe complications related to hepatobiliary surgery were reported. The median PFS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) was 19 months [95% confidence interval (CI) 16.2–21.8] and 8 months (95% CI 6.1–9.9). The median OS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) 45 months (95% CI 21.2–68.8 months) and 23 months (95% CI 13.9–32.03). Conclusions Hepatobiliary involvement is often associated with high tumor load and could require high complex multivisceral surgery. In selected patients complete cytoreduction could offer survival benefits. Morbidity related to hepatobiliary procedures is acceptable. Careful evaluation of patients and multidisciplinary approach in referral centers is mandatory.

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 ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factor ◽  
Prognostic Markers ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Advanced Ovarian Cancer ◽  
Independent Prognostic Factor ◽  
Benign Tumors ◽  
Molecular Features ◽  
Kaplan Meier

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.

scholarly journals Prognostic values of aquaporins mRNA expression in human ovarian cancer

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Mandika Chetry ◽  
Saisai Li ◽  
Hailing Liu ◽  
Xiaoli Hu ◽  
Xueqiong Zhu
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Prognostic Indicators ◽  
Transmembrane Channel ◽  
Kaplan Meier ◽  
Cancer Types ◽  
Kaplan Meier Plotter

Aquaporins (AQPs), a family of transmembrane channel, are composed of 13 identified members (AQP0–12). Accumulating evidences reported that AQPs were correlated with various biological roles and represented a prognostic predictor in various cancer types. However, the prognostic value of AQPs expression in ovarian cancer remains unclear. Using ‘Kaplan–Meier plotter’ (KM plotter) online database, we explored the predictive prognostic value of individual AQPs members’ mRNA expression to overall survival (OS) in different clinical data, such as histology, pathological grades, clinical stages, TP53 status, and applied chemotherapy in ovarian cancer patients. Our results revealed that higher AQP0, AQP1, and AQP4 mRNA expression were correlated with poor OS, whereas higher AQP3, AQP5, AQP6, AQP8, AQP10, and AQP11 showed better OS in ovarian cancer patients. Moreover, AQP4 and AQP8 showed poor OS in TP53-mutated ovarian cancer patients and AQP1 presented unfavorable OS in both TP53 mutated and wild ovarian cancer patients. Additionally, AQP3, AQP6, and AQP11 mRNA expression were correlated with better OS, whereas AQP0 and AQP1 showed poor OS in all ovarian cancer patients treated with Platin, Taxol, and Taxol + Platin chemotherapy. AQP5, AQP8, and AQP10 were associated with improved OS, however, AQP4 predicted unfavorable OS in all patients treated with Platin chemotherapy. Our results suggest that individual AQPs, except AQP2 and AQP9, are associated with unique prognostic significance and may thus act as new predictive prognostic indicators and potential drug therapeutic target in ovarian cancer.

USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer

2020 ◽  
Vol 20 (9) ◽  
pp. 689-699
Author(s):  
Xuemeng Lei ◽  
Xukun Li ◽  
Hongyan Chen ◽  
Zhihua Liu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Deubiquitinating Enzymes ◽  
Potential Therapeutic Target ◽  
Kaplan Meier ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

Background: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear. Objective: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation. Methods: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice. Results: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy. Conclusion: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.

scholarly journals 130 Prognostic significance of lymphovascular space invasion in epithelial ovarian cancer

2020 ◽  
Author(s):  
H Mansouri ◽  
I Zemni ◽  
O Jaidane ◽  
I Ben Safta ◽  
J Ben Hassouna ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Prognostic Significance ◽  
Lymphovascular Space Invasion

scholarly journals Prognostic significance of bone marrow FDG uptake in patients with gynecological cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kotaro Shimura ◽  
Seiji Mabuchi ◽  
Naoko Komura ◽  
Eriko Yokoi ◽  
Katsumi Kozasa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Poor Prognosis ◽  
Gynecological Cancer ◽  
Prognostic Significance ◽  
Standardized Uptake Value ◽  
Suppressor Cells ◽  
Underlying Mechanism ◽  
Fdg Uptake

AbstractWe investigated the prognostic significance and the underlying mechanism of increased bone marrow (BM) 2-(18F) fluoro-2-deoxy-D-glucose as a tracer (FDG)-uptake in patients with gynecological cancer. A list of patients diagnosed with cervical, endometrial, and ovarian cancer from January 2008 to December 2014 were identified. Then, through chart reviews, 559 patients who underwent staging by FDG-positron emission tomography (PET)/computed tomography (CT) and subsequent surgical resection were identified, and their clinical data were reviewed retrospectively. BM FDG-uptake was evaluated using maximum standardized uptake value (SUVmax) and BM-to-aorta uptake ratio (BAR). As a result, we have found that increased BAR was observed in 20 (8.7%), 21 (13.0%), 21 (12.6%) of cervical, endometrial, and ovarian cancer, respectively, and was associated with significantly shorter survival. Increased BAR was also closely associated with increased granulopoiesis. In vitro and in vivo experiments revealed that tumor-derived granulocyte colony-stimulating factor (G-CSF) was involved in the underlying causative mechanism of increased BM FDG-uptake, and that immune suppression mediated by G-CSF-induced myeloid-derived suppressor cells (MDSCs) is responsible for the poor prognosis of this type of cancer. In conclusion, increased BM FDG-uptake, as represented by increased BAR, is an indicator of poor prognosis in patients with gynecological cancer.

scholarly journals Comprehensive Analysis of the Expression of Key Genes Related to Hippo Signaling and Their Prognosis Impact in Ovarian Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 344
Author(s):  
Paul Kubelac ◽  
Cornelia Braicu ◽  
Lajos Raduly ◽  
Paul Chiroi ◽  
Andreea Nutu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Expression Level ◽  
Additional Patient ◽  
Tumor Control ◽  
Hippo Signaling ◽  
Patient Cohort ◽  
Qrt Pcr

The Hippo signaling pathway, one of the most conserved in humans, controlling dimensions of organs and tumor growth, is frequently deregulated in several human malignancies, including ovarian cancer (OC). The alteration of Hippo signaling has been reported to contribute to ovarian carcinogenesis and progression. However, the prognostic roles of individual Hippo genes in OC patients remain elusive. Herein we investigated the expression level and prognostic value of key Hippo genes in OC using online databases, followed by a qRT-PCR validation step in an additional patient cohort. Using the GEPIA database, we observed an increased level for TP53 and reduced expression level for LATS1, LATS2, MST1, TAZ, and TEF in tumor tissue versus normal adjacent tissue. Moreover, LATS1, LATS2, TP53, TAZ, and TEF expression levels have prognostic significance correlated with progression-free survival. The qRT-PCR validation step was conducted in an OC patient cohort comprising 29 tumor tissues and 20 normal adjacent tissues, endorsing the expression level for LATS1, LATS2, and TP53, as well as for two of the miRNAs targeting the TP53 gene, revealing miR-25-3p upregulation and miR-181c-5p downregulation. These results display that there are critical prognostic value dysregulations of the Hippo genes in OC. Our data demonstrate the major role the conserved Hippo pathway presents in tumor control, underlying potential therapeutic strategies and controlling several steps modulated by miRNAs and their target genes that could limit ovarian cancer progression.

scholarly journals The sentinel node invasion level (SNIL) as a prognostic parameter in melanoma

2021 ◽  
Author(s):  
Lutz Kretschmer ◽  
Christina Mitteldorf ◽  
Simin Hellriegel ◽  
Andreas Leha ◽  
Alexander Fichtner ◽  
...  
Keyword(s):  
Lymph Node ◽  
Prognostic Significance ◽  
Tumor Burden ◽  
Recurrence Rates ◽  
Cox Models ◽  
Nodal Basin ◽  
Lymph Vessels ◽  
Kaplan Meier ◽  
Metastasis Patterns ◽  
Transverse Sinuses

AbstractSentinel lymph node (SN) tumor burden is becoming increasingly important and is likely to be included in future N classifications in melanoma. Our aim was to investigate the prognostic significance of melanoma infiltration of various anatomically defined lymph node substructures. This retrospective cohort study included 1250 consecutive patients with SN biopsy. The pathology protocol required description of metastatic infiltration of each of the following lymph node substructures: intracapsular lymph vessels, subcapsular and transverse sinuses, cortex, paracortex, medulla, and capsule. Within the SN with the highest tumor burden, the SN invasion level (SNIL) was defined as follows: SNIL 1 = melanoma cells confined to intracapsular lymph vessels, subcapsular or transverse sinuses; SNIL 2 = melanoma infiltrating the cortex or paracortex; SNIL 3 = melanoma infiltrating the medulla or capsule. We classified 338 SN-positive patients according to the non-metric SNIL. Using Kaplan–Meier estimates and Cox models, recurrence-free survival (RFS), melanoma-specific survival (MSS) and nodal basin recurrence rates were analyzed. The median follow-up time was 75 months. The SNIL divided the SN-positive population into three groups with significantly different RFS, MSS, and nodal basin recurrence probabilities. The MSS of patients with SNIL 1 was virtually identical to that of SN-negative patients, whereas outgrowth of the metastasis from the parenchyma into the fibrous capsule or the medulla of the lymph node indicated a very poor prognosis. Thus, the SNIL may help to better assess the benefit-risk ratio of adjuvant therapies in patients with different SN metastasis patterns.

Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1

2021 ◽  
Vol 53 (5) ◽  
pp. 547-557
Author(s):  
Ya’nan Yang ◽  
Chenchen Wang ◽  
Congqi Dai ◽  
Xinyang Liu ◽  
Wenhua Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Positive Association ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
Met Amplification ◽  
Amplification Rate ◽  
Cox Proportional Hazard Regression

Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.

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