Abstract
Abstract Aging is a physiological process that is accompanied by functional decline over time. Also, aging is the single biggest risk factor for developing cancer and limitation of active cancer treatment. The number of elderly patients with colorectal cancer (CRC) has increased, however, the knowledge of the clinical outcomes of colorectal cancer in elderly patients are limited. Elderly CRC patients are a very heterogeneous population because the aging process caused complex co-morbidities and chronological age cannot predict the biological and functional changes. In this study, we analyzed cDNA microarray data using integration of receiver operating characteristic (ROC) curve and protein-protein interaction (PPI) network information, demonstrating the aging effect of cancer based on large scale data. We identified molecular features that discriminate 120 elderly (70 ≥age) and 31 young (40 ≤ age) CRC patients. Elderly group had distinct molecular features compared with the young group, and we suggest that these features may underlie the different cancer characteristics of colorectal cancer based on aging. First, we quantified the molecular features of total 15815 probes using ROC analysis. The ROC representing the performance of enolase superfamily member 1 (ENOSF1, rTS) corresponded to an area under curve (AUC) of 0.73 in the training set and 0.71 in the test set. Also the 82 differentially expressed genes (DEGs) over 2 fold with high significance (p<0.01) between the two groups, which were selected as the age-related genes. To identify the key molecules, we performed a PPI network analysis with topological metrics such as degree and betweenness centrality (BC) using the graph module.As a result, we found that down regulated EGFR, and AR could be key molecules in the PPI network having higher degree and BC scores in young group, while FOXO1, downstream signal of EGFR, was upregulated. On the other hand, the down-regulated EWSR1 and PTPN11 could be key molecules in elderly group, which were closely connected with SLC26A3 in PPI network. In previous studies, the SLC26A3 expression was significantly decreased in adenomas (polyps) and adenocarcinomas of the colon. But our result was shown the SCL26A3 overexpression in only elderly group. We suggest that elderly CRC has distinct molecular characteristics from young CRC and therefore, that the expression signatures of DEGs and PPI may improve the understanding of molecular pathogenesis and clinical behaviors in elderly CRC. Citation Format: Woo Sun Kwon, Park Daeui, Hye Ryun Kim, Hei-Cheul Jeung, Hyoung Oh Jeong, Jin-Hyuk Choi, Joong Bae Ahn, Hyun Cheol Chung, Hae Young Chung, Sun Young Rha. Molecular features reflecting biological and functional ages in elderly colorectal cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5165. doi:10.1158/1538-7445.AM2014-5165
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