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Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

ABSTRACT: OBJECTIVE:The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records. METHODS:Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N=436). RESULTS:Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (R0) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho>0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30months (log-rank p=0.002). CONCLUSIONS:Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies.

SUBMITTER: Eng KH

PROVIDER: S-EPMC5592637 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

Eng Kevin H KH Morrell Kayla K Starbuck Kristen K Spring-Robinson Chandra C Khan Aalia A Cleason Dana D Akman Levent L Zsiros Emese E Odunsi Kunle K Szender J Brian JB

Gynecologic oncology 20170508 1

<h4>Objective</h4>The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records.<h4>Methods</h4>Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tub ...[more]

PMID: 28495239

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Project description:BackgroundHigh-grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian cancer. A growing body of evidence suggests tumor-supporting roles of several members of the kallikrein-related peptidase (KLK) family, including KLK5 and KLK7, in this cancer subtype. In normal physiology, KLK5 and KLK7 are the major proteases involved in skin desquamation. Moreover, in several cancer types KLK5 and KLK7 co-expression has been observed. Recently, we have shown that elevated KLK5 mRNA levels are associated with an unfavorable prognosis in HGSOC. Therefore, the aim of this study was to investigate the clinical significance of KLK7 mRNA expression and to explore its relation to KLK5 levels in HGSOC.MethodsmRNA expression levels of KLK7 were quantified by qPCR in a well-characterized patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO III/IV, n = 139). Previously determined KLK5 mRNA as well as KLK5 and KLK7 antigen concentrations were used to evaluate the relationship between the expression patterns of both factors on the mRNA as well as protein level in tumor tissue of HGSOC patients.ResultsThere were strong, significant positive correlations between KLK5 and KLK7 both at the mRNA and the protein level, suggesting coordinate expression of these proteases in HGSOC. In univariate analyses, elevated KLK7 levels as well as the combination of KLK5 + KLK7 (high and/or high versus low/low) were significantly associated with worse progression-free survival (PFS). High mRNA expression levels of KLK7 and the combination of KLK5 and KLK7 showed a trend towards significance for overall survival (OS). In multivariate analyses, KLK7 mRNA expression represented an unfavorable, statistically significant independent predictor for PFS and OS.ConclusionsThe findings imply that both increased KLK5 and KLK7 mRNA expression levels represent unfavorable prognostic biomarkers in advanced high-grade serous ovarian cancer, whereby multivariate analyses indicate that KLK7 mRNA exhibits a stronger predictive value as compared to KLK5 mRNA and the combination of KLK5 and KLK7.

Project description:BackgroundOvarian cancer is a common gynecological malignant tumor that greatly threatens women's health, so we screened potential biomarkers of ovarian cancer and analyzed their prognostic value.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the ovarian cancer-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of ovarian cancer-related genes. The survival-related genes were screened out through the least absolute shrinkage and selection operator (LASSO) method. Multivariate Cox regression model and stepwise regression analysis were performed to construct the risk model. The receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were used to evaluate the prediction accuracy of risk score model. Finally, gene set enrichment analysis (GSEA) and immune cell infiltration analysis were performed to investigate the biological function and immune cell infiltration.ResultsA total of 111 genes were found to have common effects on survival. These genes were mainly involved in metabolism, protein phosphorylation and immune-related signaling pathways. Seven risk genes (AP3D1, DCAF10, FBXO16, LRFN4, PTPN2, SAYSD1, ZNF426) were screened out. Among these genes, AP3D1 and LRFN4 are risk genes and DCAF10, FBXO16, PTPN2, SAYSD1, and ZNF426 are protective genes. These findings suggest that risk status may be an independent prognostic factor. The risk score had a high predictive value for the prognosis of ovarian cancer. In addition, GSEA revealed that the biological function of genes expressed in patients at a high risk was mostly related to immune-related function. The contents of CD4+ T cells, macrophages, myeloid dendritic cells (mDC) and neutrophils were high in samples at a high risk for ovarian cancer.ConclusionsThe abnormal expression of AP3D1, DCAF10, FBXO16, LRFN4, PTPN2, SAYSD1 and ZNF426 is highly related to the progression of ovarian cancer. These seven genes can be used as independent prognostic markers of ovarian cancer. This study not only adds evidence to the pathogenesis of ovarian cancer but also provides scientific basis for judging the prognosis of ovarian cancer.

Dataset Information

Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

Publications

Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

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