PMID- 26264462 OWN - NLM STAT- MEDLINE DCOM- 20160317 LR - 20181113 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 13 DP - 2015 Aug 12 TI - Expression of miR-296-5p as predictive marker for radiotherapy resistance in early-stage laryngeal carcinoma. PG - 262 LID - 10.1186/s12967-015-0621-y [doi] LID - 262 AB - PURPOSE: Definitive radiation therapy is the mainstay of treatment for early stage laryngeal squamous cell carcinoma (LSCC). However, up to 30% of the patients do not respond to radiotherapy. Unfortunately, we are unable to predict which tumors are likely to respond to radiation, and which will be resistant and persist. Therefore, the development of novel markers to predict response to radiotherapy is urgently needed. This study was designed to evaluate the expression pattern of microRNAs (miRNAs) in LSCC in order to identify markers capable of segregating radioresistant and radiosensitive tumors and to investigate the relationship between the expression of these miRNAs and the prognosis of LSCC. METHODS: The expression profile of 667 miRNAs was determined in an initial screening of nine early-stage LSCC samples (5 radioresistant and 4 radiosensitive) using TaqMan Low-Density Array (TLDA). Real-time polymerase chain reactions were performed to validate the expression of selected miRNAs in an expanded LSCC cohort (20 radioresistant and 14 radiosensitive). The miRNA expression level was scored as high or low based on the median of the expression in the LSCC samples. RESULTS: A comprehensive miRNA expression profiling enabled the identification of four miRNAs (miR-296-5p miR-452, miR-183* and miR-200c) differentially expressed in radioresistant LSCC. Moreover, the analysis of additional 34 LSCC samples, confirmed the expression of miR-296-5p as significantly related to radioresistance (p = 0.002) as well as an association of this marker with recurrence (p = 0.025) in early stage laryngeal cancer. CONCLUSIONS: This study indicates that miR-296-5p expression is associated with resistance to radiotherapy and tumor recurrence in early stage LSCC, showing the feasibility of this marker as a novel prognostic factor for this malignance. Furthermore, miR-296-5p expression could be helpful in the identification of tumors resistant to radiotherapy; thus aiding the clinicians in the choice of the best therapeutic scheme to be used in each case. FAU - Maia, Danielle AU - Maia D AD - Laboratory of Molecular Cancer Biology, Department of Biological Sciences, Federal University of Sao Paulo, Rua Pedro de Toledo, 669-11 degrees andar, Sao Paulo, SP, 04039-032, Brazil. dellymaia@gmail.com. FAU - de Carvalho, Ana Carolina AU - de Carvalho AC AD - Laboratory of Molecular Cancer Biology, Department of Biological Sciences, Federal University of Sao Paulo, Rua Pedro de Toledo, 669-11 degrees andar, Sao Paulo, SP, 04039-032, Brazil. ca_oak@yahoo.com.br. AD - Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331, Barretos, SP, 14784-400, Brazil. ca_oak@yahoo.com.br. FAU - Horst, Maria Aderuza AU - Horst MA AD - Laboratory of Molecular Cancer Biology, Department of Biological Sciences, Federal University of Sao Paulo, Rua Pedro de Toledo, 669-11 degrees andar, Sao Paulo, SP, 04039-032, Brazil. aderuza@gmail.com. FAU - Carvalho, Andre Lopes AU - Carvalho AL AD - Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331, Barretos, SP, 14784-400, Brazil. alopescarvalho@uol.com.br. AD - Department of Head and Neck Surgery, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, 14784-400, Brazil. alopescarvalho@uol.com.br. FAU - Scapulatempo-Neto, Cristovam AU - Scapulatempo-Neto C AD - Department of Pathology, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, 14784-400, Brazil. cristovamscapula@uol.com.br. FAU - Vettore, Andre Luiz AU - Vettore AL AD - Laboratory of Molecular Cancer Biology, Department of Biological Sciences, Federal University of Sao Paulo, Rua Pedro de Toledo, 669-11 degrees andar, Sao Paulo, SP, 04039-032, Brazil. andre.vettore@gmail.com. AD - Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore. andre.vettore@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150812 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (Biomarkers, Tumor) RN - 0 (MIRN296 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics MH - Female MH - Gene Expression Profiling MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Laryngeal Neoplasms/*genetics/pathology/*radiotherapy MH - Male MH - MicroRNAs/*genetics/metabolism MH - Middle Aged MH - Neoplasm Staging MH - Neoplasms, Squamous Cell/genetics/pathology/radiotherapy MH - Prognosis MH - Radiation Tolerance/*genetics MH - Survival Analysis PMC - PMC4533949 EDAT- 2015/08/13 06:00 MHDA- 2016/03/18 06:00 PMCR- 2015/08/12 CRDT- 2015/08/13 06:00 PHST- 2015/03/08 00:00 [received] PHST- 2015/07/28 00:00 [accepted] PHST- 2015/08/13 06:00 [entrez] PHST- 2015/08/13 06:00 [pubmed] PHST- 2016/03/18 06:00 [medline] PHST- 2015/08/12 00:00 [pmc-release] AID - 10.1186/s12967-015-0621-y [pii] AID - 621 [pii] AID - 10.1186/s12967-015-0621-y [doi] PST - epublish SO - J Transl Med. 2015 Aug 12;13:262. doi: 10.1186/s12967-015-0621-y.