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• W2023572628 abstract "Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLIntroduction: MiRNA are potentially important moderators of chemoresponse in human cancer due to their widespread regulatory function. Identification of a set of clinically validated and biologically relevant miRNA could serve as potential markers for prognostication, chemoresponse prediction, and novel therapeutic targets. The objective of this study was to utilize population, clinical, and cell-line data as an integrative approach to identifying miRNA showing a consistent association with chemoresponse.Materials and Methods: Patients diagnosed with squamous cell carcinomas of the lung between 2004 and 2007 were retrieved from the linked SEER-Medicare database with data on tumor TNM markers, grade, survival, and treatment information (N=6,215). Medicare HCPCS and Revenue codes were used to identify patients receiving cisplatin (N=142), carboplatin (N=1,125), etoposide, (N=37), and paclitaxel (N=779). The AJCC TNM markers and grade were used to partition patients into disjoint groups indicative of tumor progression, with the average survival being calculated for each group. A second set of clinical data containing miRNA expression (N=57, GSE 16025) was partitioned in the same manner, with the average miRNA expression on 328 probes being calculated for each group. Linear regression was used to estimate the association between miRNA expression in the clinical cohort and survival in the population sample given similar tumor characteristics. This analysis was also performed on two subsets of patients receiving surgery and chemotherapy both with and without preoperative radiation. A second analysis utilizing the NCI-60 anti-cancer screen estimated the association between miRNA expression and the amount of each chemotherapeutic agent needed for 50% growth-inhibition in an experimental setting. MiRNA which showed a significant association in at least one of the analyses and concordance in all others were considered for further analysis using IPA software.Results: Multiple miRNA showed consistent associations with chemoresponse across analytic approaches as well as having documented interactions with molecular species known to play a role in human cancers. Notably, over-expression of miR-25, 27a, 141, and 181a showed a strong association with chemosensitivity in three of the four agents considered and formed an interaction network including transcriptional regulation, HDAC, and EGF activity. Over-expression of miR-133b was associated with chemoresistance in three of four agents. Numerous other miRNA formed networks specific to a single agent.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 147. doi:10.1158/1538-7445.AM2011-147" @default.
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• W2023572628 title "Abstract 147: Identification of miRNA associated with chemoresponse using combined clinical, population, and cellular data in lung cancer" @default.
• W2023572628 doi "https://doi.org/10.1158/1538-7445.am2011-147" @default.
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