Predicting the clinical behavior of ovarian cancer from gene expression profiles

Abstract

We investigated whether prognostic information is reflected in the expression patterns of ovarian carcinoma samples. RNA obtained from seven FIGO stage I without recurrence, seven platin-sensitive advanced-stage (III or IV), and six platin-resistant advanced-stage ovarian tumors was hybridized on a complementary DNA microarray with 21,372 spotted clones. The results revealed that a considerable number of genes exhibit nonaccidental differential expression between the different tumor classes. Principal component analysis reflected the differences between the three tumor classes and their order of transition. Using a leave-one-out approach together with least squares support vector machines, we obtained an estimated classification test accuracy of 100% for the distinction between stage I and advanced-stage disease and 76.92% for the distinction between platin-resistant versus platin-sensitive disease in FIGO stage III/IV. These results indicate that gene expression patterns could be useful in clinical management of ovarian cancer.

The role of regulatory T cells in ovarian cancer

“…The reviewed clinical and experimental studies clearly suggest that T reg are important mediators of undesired immune tolerance in ovarian cancer patients, mirrored by an inverse correlation of intratumoral T reg with patient survival. With recent studies demonstrating gene expression profiling as a promising new tool for the detection of chemoresistant ovary cancers (3,4) , it may be possible to identify a subgroup of patients that in particular could benefit from the treatment approaches outlined in this review. While there are still many open questions, it is becoming more and more evident that inhibition of T reg could be a promising therapeutic option for ovarian cancer patients and should be subject to further clinical studies.…”

“…At time of primary diagnosis, about 75% of the patients present with advanced‐stage disease of which 20–30% are primarily resistant to chemotherapy (1) . Depending on its specific molecular aberrations, an initially platinum‐sensitive cancer is also likely to eventually acquire chemoresistance (3,4) . These findings are reflected by a 5‐year survival rate of less than 20% in patients with FIGO stage III/IV disease.…”

Methodology in plasma proteomic pattern experiments

“…However, even cross-validation is prone to an underestimation of the error rate, and the authors do not mention whether this cross-validation was performed before or after selection of the possible markers (2) . Note that the generalization performance can only be estimated in a reliable way in case the entire modelbuilding process, including the selection of the informative markers, is repeated for each cross-validation training set (3) . Furthermore, since the tumors used to build the predictor may not reflect all characteristics of the population of interest, it is still preferable to use an independent test set to overcome this problem.…”

M@CBETH: Optimizing Clinical Microarray Classi.cation

“…The mean of the replicate and normalized logratios (i.e., patient over reference) was used as a measure for expression. More detailed information can be found in [1].…”