TY - JOUR
T1 - MALDI-imaging identifies overexpression of Thymosin beta-4 (TYB4) as amarker for aneuploid colorectal cancer
AU - T., Gemoll
AU - S., Strohkamp
AU - K., Schillo
AU - C., Thorns
AU - J.K., Habermann
PY - 2016
Y1 - 2016
N2 - Background DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. In this study, we compared diploid and aneuploid colon cancer tissues against normal mucosa of the colon by means of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). Material and Methods DNA image cytometry determined the ploidy status of tissue samples that were subsequently subjected to MALDI-IMS. After obtaining protein profiles through direct analysis of tissue sections, a discovery and a validation set were used to predict ploidy and disease status by applying proteomic classification algorithms [Supervised Neural Network (SNN) and Receiver Operating Characteristic (ROC)]. Clinical target validation was performed by immunohistochemistry using tissue microarrays (TMA) comprising healthy controls as well as diploid and aneuploid colorectal carcinomas. Results SNN algorithm categorized 99% of normal mucosa and 90% of colon carcinoma as well as 99% of diploid and 94% of aneuploid colon cancers correctly. Validation of both comparisons showed a correct classification of normal mucosa in 92%, tumors in 96%, and diploid and aneuploid colon cancers in 92% and 78%, respectively. Five peaks (m/z 2,396 and 4,977 for the diploid vs. aneuploid comparison and m/z 3,375, 6,663, 8,581 for the normal mucosa vs. carcinoma comparison) reached significance in both SNN and ROC analysis. Among these,m/z 4,977was identified as thymosin beta 4 (TYB4). TYB4 showed expression differences also in clinical samples using a tissue microarray of normal mucosa, diploid and aneuploid colorectal carcinomas and serve to predict overall survival. Conclusion Our data underscore the potential of MALDI-IMS proteomic algorithms to reveal significant molecular details from distinct tumor subtypes such as different ploidy types. Tβ-4 was validated in clinical samples using a tissue microarray to predict overall survival in colorectal cancer patients.
AB - Background DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. In this study, we compared diploid and aneuploid colon cancer tissues against normal mucosa of the colon by means of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). Material and Methods DNA image cytometry determined the ploidy status of tissue samples that were subsequently subjected to MALDI-IMS. After obtaining protein profiles through direct analysis of tissue sections, a discovery and a validation set were used to predict ploidy and disease status by applying proteomic classification algorithms [Supervised Neural Network (SNN) and Receiver Operating Characteristic (ROC)]. Clinical target validation was performed by immunohistochemistry using tissue microarrays (TMA) comprising healthy controls as well as diploid and aneuploid colorectal carcinomas. Results SNN algorithm categorized 99% of normal mucosa and 90% of colon carcinoma as well as 99% of diploid and 94% of aneuploid colon cancers correctly. Validation of both comparisons showed a correct classification of normal mucosa in 92%, tumors in 96%, and diploid and aneuploid colon cancers in 92% and 78%, respectively. Five peaks (m/z 2,396 and 4,977 for the diploid vs. aneuploid comparison and m/z 3,375, 6,663, 8,581 for the normal mucosa vs. carcinoma comparison) reached significance in both SNN and ROC analysis. Among these,m/z 4,977was identified as thymosin beta 4 (TYB4). TYB4 showed expression differences also in clinical samples using a tissue microarray of normal mucosa, diploid and aneuploid colorectal carcinomas and serve to predict overall survival. Conclusion Our data underscore the potential of MALDI-IMS proteomic algorithms to reveal significant molecular details from distinct tumor subtypes such as different ploidy types. Tβ-4 was validated in clinical samples using a tissue microarray to predict overall survival in colorectal cancer patients.
UR - http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L72227414
http://dx.doi.org/10.1007/s11825-016-0083-5
UR - http://www.mendeley.com/research/maldiimaging-identifies-overexpression-thymosin-beta4-tyb4-amarker-aneuploid-colorectal-cancer
U2 - 10.1007/s11825-016-0083-5
DO - 10.1007/s11825-016-0083-5
M3 - Zeitschriftenaufsätze
SN - 0936-5931
VL - 28
SP - 135
JO - Medizinische Genetik
JF - Medizinische Genetik
IS - 1
ER -
