Abstract
Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in head and neck cancer (HNC). The aim of the present study was to evaluate plasma levels of three lncRNA molecules (lincRNA-p21, GAS5, and HOTAIR) in the treatment response in HNC patients treated with radical chemoradiotherapy (CRT). Forty-one patients with HNC were enrolled in the study. Most of the patients had nasopharyngeal carcinoma (n = 27, 65.9 %) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5 months after therapy. lncRNAs in plasma were measured by semiquantitative PCR. Treatment response was evaluated according to clinical examination, RECIST and PERCIST criteria based on magnetic resonance imaging (MRI), and positron emission tomography with computed tomography (PET/CT) findings. Complete response (CR) rates were 73.2, 36.6, and 50 % for clinical investigation, PET/CT-, or MRI-based response evaluation, respectively. Predictive value of lncRNAs was investigated in patients with CR vs. those with partial response (PR)/progressive disease (PD). We found that post-treatment GAS5 levels in patients with PR/PD were significantly higher compared with patients with CR based on clinical investigation (p = 0.01). Receiver operator characteristic (ROC) analysis showed that at a cutoff value of 0.3 of GAS5, sensitivity and specificity for clinical tumor response were 82 and 77 %, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (p = 0.042). In contrast to GAS5, pretreatment or post-treatment lincRNA-p21 and HOTAIR levels were not informative for treatment response. Our results suggest that circulating GAS5 could be a biomarker in predicting treatment response in HNC patients.
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References
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA: A Cancer J Clin. 2005;55(2):74–108.
Belcher R, Hayes K, Fedewa S, Chen AY. Current treatment of head and neck squamous cell cancer. J Surg Oncol. 2014;110(5):551–74. doi:10.1002/jso.23724.
Deschler DG, Richmon JD, Khariwala SS, Ferris RL, Wang MB. The “new” head and neck cancer patient-young, nonsmoker, nondrinker, and HPV positive: evaluation. Otolaryngol-Head Neck Surg: Off J Am Acad Otolaryngol-Head Neck Surg. 2014;151(3):375–80. doi:10.1177/0194599814538605.
Cherukuri DP, Nelson MA. Do elevated levels of eicosanoids play a role in head and neck cancer recurrence and metastasis? Implications for prevention and treatment. Cancer Biol Ther. 2004;3(9):853–4.
Kawecki A, Krajewski R. Follow-up in patients treated for head and neck cancer. Memo. 2014;7(2):87–91. doi:10.1007/s12254-014-0143-y.
Lee JH, Song JH, Lee SN, Kang JH, Kim MS, Sun DI, et al. Adjuvant postoperative radiotherapy with or without chemotherapy for locally advanced squamous cell carcinoma of the head and neck: the importance of patient selection for the postoperative chemoradiotherapy. Cancer Res Treat: Off J Kor Cancer Assoc. 2013;45(1):31–9. doi:10.4143/crt.2013.45.1.31.
Pignon JP, le Maitre A, Maillard E, Bourhis J, Group M-NC. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4–14. doi:10.1016/j.radonc.2009.04.014.
Busch CJ, Tribius S, Schafhausen P, Knecht R. The current role of systemic chemotherapy in the primary treatment of head and neck cancer. Cancer Treat Rev. 2015;41(3):217–21. doi:10.1016/j.ctrv.2015.02.002.
Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, et al. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the radiation therapy oncology group 0129 trial: long-term report of efficacy and toxicity. J Clin Oncol: Off J Am Soc Clin Oncol. 2014;32(34):3858–66. doi:10.1200/JCO.2014.55.3925.
Sita-Lumsden A, Fletcher CE, Dart DA, Brooke GN, Waxman J, Bevan CL. Circulating nucleic acids as biomarkers of prostate cancer. Biomark Med. 2013;7(6):867–77. doi:10.2217/bmm.13.104.
Sita-Lumsden A, Dart DA, Waxman J, Bevan CL. Circulating microRNAs as potential new biomarkers for prostate cancer. Br J Cancer. 2013;108(10):1925–30. doi:10.1038/bjc.2013.192.
Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012;482(7385):339–46. doi:10.1038/nature10887.
Hansji H, Leung EY, Baguley BC, Finlay GJ, Askarian-Amiri ME. Keeping abreast with long non-coding RNAs in mammary gland development and breast cancer. Front Genet. 2014;5:379. doi:10.3389/fgene.2014.00379.
Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9(6):703–19. doi:10.4161/rna.20481.
Arita T, Ichikawa D, Konishi H, Komatsu S, Shiozaki A, Shoda K, et al. Circulating long non-coding RNAs in plasma of patients with gastric cancer. Anticancer Res. 2013;33(8):3185–93.
Isin M, Ozgur E, Cetin G, Erten N, Aktan M, Gezer U, et al. Investigation of circulating lncRNAs in B-cell neoplasms. Clin Chim Acta; Int J Clin Chem. 2014;431:255–9. doi:10.1016/j.cca.2014.02.010.
Tong YS, Wang XW, Zhou XL, Liu ZH, Yang TX, Shi WH, et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer. 2015;14:3. doi:10.1186/1476-4598-14-3.
Yang QQ, Deng YF. Genome-wide analysis of long non-coding RNA in primary nasopharyngeal carcinoma by microarray. Histopathology. 2015;66(7):1022–30. doi:10.1111/his.12616.
Pickard MR, Williams GT. Molecular and cellular mechanisms of action of tumour suppressor GAS5 LncRNA. Genes (Basel). 2015;6(3):484–99. doi:10.3390/genes6030484.
Tang SS, Zheng BY, Xiong XD. LincRNA-p21: implications in human diseases. Int J Mol Sci. 2015;16(8):18732–40. doi:10.3390/ijms160818732.
Yu X, Li Z. Long non-coding RNA HOTAIR: a novel oncogene (review). Mol Med Rep. 2015. doi:10.3892/mmr.2015.4161.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. doi:10.1016/j.ejca.2008.10.026.
Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med: Off Publ, Soc Nucl Med. 2009;50 Suppl 1:122S–50. doi:10.2967/jnumed.108.057307.
Ozgur E, Mert U, Isin M, Okutan M, Dalay N, Gezer U. Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells. Clin Exp Med. 2013;13(2):119–26. doi:10.1007/s10238-012-0181-x.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30. doi:10.3322/caac.21166.
Ho AS, Tsao GJ, Chen FW, Shen T, Kaplan MJ, Colevas AD, et al. Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence. Cancer. 2013;119(7):1349–56. doi:10.1002/cncr.27892.
Zhou X, Yin C, Dang Y, Ye F, Zhang G. Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep. 2015;5:11516. doi:10.1038/srep11516.
Gee HE, Buffa FM, Camps C, Ramachandran A, Leek R, Taylor M, et al. The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis. Br J Cancer. 2011;104(7):1168–77. doi:10.1038/sj.bjc.6606076.
Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28(2):195–208. doi:10.1038/onc.2008.373.
Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta. 2013;1832(10):1613–23. doi:10.1016/j.bbadis.2013.05.005.
Qiao HP, Gao WS, Huo JX, Yang ZS. Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev. 2013;14(2):1077–82.
Cao S, Liu W, Li F, Zhao W, Qin C. Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int J Clin Exp Pathol. 2014;7(10):6776–83.
Yin D, He X, Zhang E, Kong R, De W, Zhang Z. Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med Oncol. 2014;31(11):253. doi:10.1007/s12032-014-0253-8.
Qin R, Chen Z, Ding Y, Hao J, Hu J, Guo F. Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. Neoplasma. 2013;60(5):486–92. doi:10.4149/neo_2013_063.
Dong S, Qu X, Li W, Zhong X, Li P, Yang S, et al. The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol. 2015;8:43. doi:10.1186/s13045-015-0140-6.
Zhai H, Fesler A, Schee K, Fodstad O, Flatmark K, Ju J. Clinical significance of long intergenic noncoding RNA-p21 in colorectal cancer. Clin Colorectal Cancer. 2013;12(4):261–6. doi:10.1016/j.clcc.2013.06.003.
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6. doi:10.1038/nature08975.
Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6. doi:10.1158/0008-5472.CAN-11-1021.
Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, et al. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 2011;18(5):1243–50. doi:10.1245/s10434-011-1581-y.
Tantiwongkosi B, Yu F, Kanard A, Miller FR. Role of (18)F-FDG PET/CT in pre and post treatment evaluation in head and neck carcinoma. World J Radiol. 2014;6(5):177–91. doi:10.4329/wjr.v6.i5.177.
Bronstein AD, Nyberg DA, Schwartz AN, Shuman WP, Griffin BR. Soft-tissue changes after head and neck radiation: CT findings. AJNR Am J Neuroradiol. 1989;10(1):171–5.
Gupta T, Master Z, Kannan S, Agarwal JP, Ghsoh-Laskar S, Rangarajan V, et al. Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2011;38(11):2083–95. doi:10.1007/s00259-011-1893-y.
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We would like to thank Atilla Bozdogan for performing the statistical analysis.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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The study was funded by Istanbul University Scientific Research Projects Coordination Unit (no: 28278).
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Fayda, M., Isin, M., Tambas, M. et al. Do circulating long non-coding RNAs (lncRNAs) (LincRNA-p21, GAS 5, HOTAIR) predict the treatment response in patients with head and neck cancer treated with chemoradiotherapy?. Tumor Biol. 37, 3969–3978 (2016). https://doi.org/10.1007/s13277-015-4189-1
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DOI: https://doi.org/10.1007/s13277-015-4189-1