Prediction of ovarian cancer prognosis and response to chemotherapy by a serum-based multiparametric biomarker panel

Abstract

Currently, there are no effective biomarkers for ovarian cancer prognosis or prediction of therapeutic response. The objective of this study was to examine a panel of 10 serum biochemical parameters for their ability to predict response to chemotherapy, progression and survival of ovarian cancer patients. Sera from ovarian cancer patients were collected prior and during chemotherapy and were analysed by enzyme-linked immunosorbent assay for CA125, kallikreins 5, 6, 7, 8, 10 and 11, B7-H4, regenerating protein IV and Spondin-2. The odds ratio and hazard ratio and their 95% confidence interval (95% CI) were calculated. Time-dependent receiver-operating characteristic (ROC) curves were utilised to evaluate the prognostic performance of the biomarkers. The levels of several markers at baseline (c0), or after the first chemotherapy cycle (rc1), predicted chemotherapy response and overall or progression-free survival in univariate analysis. A multiparametric model (c0 of CA125, KLK5, KLK7 and rc1 of CA125) provided predictive accuracy with area under the ROC curve (AUC) of 0.82 (0.62 after correction for overfitting). Another marker combination (c0 of KLK7, KLK10, B7-H4, Spondin-2) was useful in predicting short-term (1-year) survival with an AUC of 0.89 (0.74 after correction for overfitting). All markers examined, except KLK7 and regenerating protein IV, were powerful predictors of time to progression (TTP) among chemotherapy responders. Individual and panels of biomarkers from the kallikrein family (and other families) can predict response to chemotherapy, overall survival, short-term (1-year) survival, progression-free survival and TTP of ovarian cancer patients treated with chemotherapy.

B7-H4 Expression is Associated with Cancer Progression and Predicts Patient Survival in Human Thyroid Cancer

“…B7-H4 expression was significantly higher in invasive breast cancer cells and increased B7-H4 expression was associated with negative progesterone receptor status in breast cancer patients (Tringler et al, 2005). Furthermore, the measurement of B7-H4 expression is expected to become a useful tool for the prediction of chemotherapeutic response and prognosis in ovarian cancer patients and gastric cancer patients (Oikonomopoulou et al, 2008;Arigami et al, 2010). In the present study, primary thyroid tumor cells displayed various degrees of B7-H4 expression, and its expression was observed in 95.3% patients with thyroid cancer.…”

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance

“…The latest data propose that KLK5 could also constitute a very helpful serological biomarker of unfavorable prognosis in ovarian malignancies after the observation of the correlation between the KLK5 serum concentration and the progression-free survival period of the patients (Dorn et al , 2011b ). Additionally, a drop in KLK5 serum concentration after the fi rst chemotherapy cycle has been associated with subsequent effi cient chemotherapy response (Oikonomopoulou et al , 2008b ). Furthermore, increased KLK5 and KLK7 protein concentration in cytosolic extracts have been correlated with unfavorable prognosis, whereas elevated KLK8, KLK11, and KLK13 protein concentrations in cytosolic extracts have been correlated with favorable outcome (Yousef and Diamandis , 2009 ).…”

“…Apart from their physiological roles, PARs can intervene in cancer-associated molecular cascades affecting cell proliferation and migration (Hollenberg et al , 2008 ;Oikonomopoulou et al , 2010b ). Given that IGFBPs and PARs are well-documented substrates of KLKs, an abnormal Kwiatkowski et al , 1998 ;Magklara et al , 1999 ;Nam et al , 2000 ;Steuber et al , 2007 PSA/KLK3 Screening; diagnosis; treatment monitoring; unfavorable prognosis Stephan et al , 2007 ;Lilja et al , 2008 ;Ulmert et al , 2009 ;Avgeris et al , 2010 KLK4 Unfavorable prognosis Avgeris et al , 2011b KLK5 Favorable prognosis Yousef et al , 2002b ;Korbakis et al , 2009 KLK11 Diagnosis; favorable prognosis Diamandis et al , 2002 ;Nakamura et al , 2003a,b ;Bi et al , 2010 KLK14 Unfavorable prognosis Yousef et al , 2003e ;Rabien et al , 2008 KLK15 Unfavorable prognosis Mavridis et al , 2010a ;Rabien et al , 2010 Breast cancer PSA/KLK3 Diagnosis; treatment response; favorable prognosis Yu et al , 1998 ;Foekens et al , 1999 ;Black et al , 2000 ;Sauter et al , 2004a Kim et al , 2001 ;Diamandis et al , 2003a ;Dong et al , 2003 ;Yousef et al , 2003b ;Oikonomopoulou et al , 2008b ;Dorn et al , 2011a,b KLK6 Diagnosis; unfavorable prognosis Diamandis et al , 2000Diamandis et al , , 2003bHoffman et al , 2002 ;Shih Ie et al , 2007 ;Kountourakis et a...…”

“…Many biomarker panels containing several members of the KLK family, such as KLK5, KLK6, KLK7, KLK8, KLK10, KLK11, and KLK13 along with non-KLK markers, namely, CA125, V-set domain containing T cell activation inhibitor 1 (VTCN1), regenerating islet-derived family, member 4 protein (REG4), and spondin 2, whose expression is determined in sera or tissues of ovarian cancer patients, have been proposed as useful predictors of response to chemotherapy, as well as the DFS, OS, and time-to-progression intervals of the treated patients (Zheng et al , 2007 ;Oikonomopoulou et al , 2008b ).…”

HE4 protein and SMRP: Potential novel biomarkers in ovarian cancer detection

“…Although certain ovarian cancer screening tests have been shown to decrease mortality rates, the possibility of efficient screening that may be used in everyday practice remains elusive. Measurement of serum CA125 antigen remains the gold standard (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”