Prognostic gene expression signature for high-grade serous ovarian cancer.

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches

A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases

This study is supported by research funds from Cancer Research Society of Canada (19319). NSM is supported by the NSW Ministry of Health and UNSW Sydney under the NSW Health PhD Scholarship Program, and the Translational Cancer Research Network, a translational cancer research center program funded by the Cancer Institute NSW. The Gynaecological Oncology Biobank at Westmead was funded by Cancer Institute NSW (12/RIG/1–17 and 15/RIG/1–16) and the National Health and Medical Research Council of Australia (ID310670, ID628903). FM is funded by University of Pittsburgh School of Medicine Dean's Faculty Advancement Award. The HOPE study is funded by: US National Cancer Institute (K07-CA80668, P50-CA159981, R01CA095023), US Army Medical Research and Materiel Command (DAMD17–02–1–0669) and NIH/National Center for Research Resources/General Clinical Research Center (MO1- RR000056). KS is funded by the Swedish Cancer foundation. The Generations Study thank Breast Cancer Now, the Institute of Cancer Research and Ovarian Cancer Action for support and funding. The ICR acknowledge NHS funding to the NIHR Biomedical Research Centre. Tissue samples for GER were provided by the tissue bank of the National Center for Tumor Diseases (NCT, Heidelberg, Germany) in accordance with the regulations of the tissue bank and the approval of the ethics committee of the University of Heidelberg. The Health Science Alliance (HSA) Biobank acknowledges the UNSW Biorepository, UNSW Sydney, Australia. We thank Shuhong Liu, Young Ou, and Deon Richards for immunohistochemical stains, and Thomas Kryton, BFA, digital imaging specialist for Alberta Public Lab for creating the figures. We especially thank all the study participants, health care staff and data providers internationally who have made this research possible

A comparison of two quality-of-life questionnaires for cancer clinical trials: the functional living index--cancer (FLIC) and the quality of life questionnaire core module (QLQ-C30).

Choosing a measure instrument for a study raises the question of whether instruments designed for the same purpose produce the same results. We investigated this question for two instruments designed to measure subjective quality of life (QOL) in cancer clinical trials: the Functional Living Index-Cancer (FLIC) and the Quality of Life Questionnaire Core module (QLQ-C30). These were administered concurrently to 98 cancer patients. Four patient groups were defined: (1) well, no chemotherapy (n = 23); (2) adjuvant chemotherapy (n = 24); (3) stable disease, active chemotherapy (n = 24); (4) progressive disease (n = 27). Both instruments have global, role, social, emotional, pain, and nausea scales; QLQ-C30 also assesses physical function, cognitive function, and fatigue, while FLIC assesses hardship. Correlation analysis indicated convergent validity for the global, role, emotional, pain and nausea dimensions, but not the social dimension. Both instruments indicated that groups 1 and 2 had better QOL than group 4 in at least one dimension. However, different dimension-specific results meant that qualitatively different conclusions would have been drawn if either instrument had been used singly: FLIC indicated that group 1 had better role function that group 4 and suffered less hardship and that group 1 suffered less nausea than group 3, while the QLQ-C30 data indicated that group 2 had better physical function than group 4. The only consistent result was for pain: both instruments indicated group 4 had more pain than either groups 1 or 2. Thus the choice of QOL instrument for use in a particular trial will affect both the results and conclusions. It is important, therefore, to consider carefully which instrument is most likely to detect important differences relevant to the patients' lives in that setting

Managing quality in cancer services: why improvement isn't easy.

Optimising the quality of care is an imperative for health services worldwide, including in Australia. Recognition that poor quality often has its roots in system failures is beginning to shift strategies for improvement to the systems of care, although the tendency remains to focus on eliminating the practice variations of individual clinicians. In those instances where systems improvement is addressed, strategies tend to be generic and technical, and often unrelated to the context in which they are applied. This paper reports an interim evaluation of a quality management program in cancer services implemented in a Sydney metropolitan teaching hospital dispersed across multiple campuses. The paper aims to inform the debate on quality improvement by reporting not only on what was achieved, but why change seems to be so hard. We found that organisational and social factors that influence the quality of health services were not sufficiently addressed, compared with technical factors. We conclude that service quality needs to be repositioned as an organisational goal, and implemented via a structured process that addresses organisational and social factors, as well as technical factors

Signalling mechanisms underlying subversion of the immune response by the filarial nematode secreted product ES-62

Secretion of immunomodulatory molecules is a key strategy employed by pathogens to enable their survival in host organisms. For example, arthropod-transmitted filarial nematodes, which achieve longevity within the infected host by suppressing and modulating the host immune response, produce excretory–secretory (ES) products that have been demonstrated to possess immunomodulatory properties. In this review we discuss the immunomodulatory effects of the phosphorylcholine-containing filarial nematode-secreted glycoprotein ES-62 and describe the intracellular signal transduction pathways it targets to achieve these effects