Classification and Biomarker Discovery in Cancer Studies Using a Differential Protein Mapping Method Combined with Mass Spectrometry.

[摘要] Cancer remains a major public health challenge. The high mortality rateassociated with cancer is due in part to the delay of diagnosis which results from the lateclinical manifestation of tumors. Identification of biomarkers that can be used to classifytumors should provide more specific and effective strategies for detection, as well asimprove monitoring of tumor progression. Several studies were performed in this work.The first study mapped protein expression for a total of 18 samples which includeovarian serous, ovarian surface epithelium, ovarian clear cell, endometrioid carcinomaand breast epithelial cell lines using an automated 2-D liquid fractionation system.Hierarchical clustering analysis was used to classify the different samples according totheir protein expression profiles showing that specific types of serous carcinoma cell linestend to cluster together and different types of cancers can be classified. Potential markerbands used to classify different subtypes of individual cancer can be identified. As anoutgrowth of this initial study, the mass mapping technique was also applied to theovarian serous carcinoma cell lines.In a second study, the 2-D liquid mapping method was also applied tocharacterize global protein expression patterns in 19 ovarian serous carcinoma tissuesamples to develop novel diagnostic biomarkers and allow molecular classification.Nineteen tissue samples could be classified into two different groups with one groupassociated with stage I and the other group associated with stage III and IV. Proteins thatwere differentially expressed in different groups were selected for identification byMALDI-TOF-MS or MALDI QIT TOF or LTQ MS. Fifteen of the selected proteins wereunequivocally identified as up-regulated in low stage and 45 of the proteins were downregulated.These proteins are known to play an important role in cellular functions andmay serve as markers of ovarian serous carcinomas. Studies were also applied to themembrane glyco-proteome using different breast cancer cell lines CA1a and AT1 usingmultiple lectin extraction where differential proteins were identified using ESI-MS/MS.

[发布机构] University of Michigan

[效力级别] Mass Spectrometry

[关键词] Liquid Phase Separation;Mass Spectrometry;Ovarian;PF2D;Two Dimensional;Classification;Chemistry;Science;Chemistry