Skip to main content
Top
Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

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?

Authors: Merdan Fayda, Mustafa Isin, Makbule Tambas, Murat Guveli, Rasim Meral, Musa Altun, Dilek Sahin, Gozde Ozkan, Yasemin Sanli, Husniye Isin, Emre Ozgur, Ugur Gezer

Published in: Tumor Biology | Issue 3/2016

Login to get access

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.
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA: A Cancer J Clin. 2005;55(2):74–108. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA: A Cancer J Clin. 2005;55(2):74–108.
3.
go back to reference 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.CrossRef 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​.CrossRef
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.PubMed 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.PubMed
19.
go back to reference 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. 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.
23.
go back to reference 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.CrossRef 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.CrossRef
24.
26.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
31.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
32.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
34.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
35.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
38.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
39.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
41.
go back to reference 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.PubMed 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.PubMed
42.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
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?
Authors
Merdan Fayda
Mustafa Isin
Makbule Tambas
Murat Guveli
Rasim Meral
Musa Altun
Dilek Sahin
Gozde Ozkan
Yasemin Sanli
Husniye Isin
Emre Ozgur
Ugur Gezer
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4189-1

Other articles of this Issue 3/2016

Tumor Biology 3/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine