HOTAIR is a predictive and prognostic biomarker for patients with advanced gastric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy.

Accumulating evidence suggests that long non-coding RNA (lncRNA) HOTAIR participates in many types of cancer such as gastric cancer and may confer malignant phenotype to tumor cells. Fluorouracil and platinum combination chemotherapy is the first line therapy for gastric cancer. However, it is still unknown whether HOTAIR influences the outcome of cancer patients treated with chemotherapy. This study aimed to evaluate the association of HOTAIR expression with the prognosis of patients with advanced gastric adenocarcinoma (GA) receiving fluorouracil and platinum based chemotherapy. We examined the levels of HOTAIR in 168 GA samples using quantitative real-time PCR and analyzed its relationship with clinical features and prognosis of patients with advanced GA treated with fluorouracil and platinum based chemotherapy. Compared with paracancerous tissues, HOTAIR was significantly upregulated in GA tissues, especially in more advanced cases. High HOTAIR expression was an independent poor prognostic factor for patients with advanced GA. Further stratification analyses revealed that the association between HOTAIR expression and survival in patients with advanced GA remained significant in the subgroup of patients with TNM stages IIIA and IIIB, poorly differentiated, and smaller tumors. In conclusion, our results provide first evidence that HOTAIR may be served as a biomarker that predicts which patient with advanced GA will benefit from fluorouracil and platinum combination chemotherapy.

[1]  Ming Sun,et al.  Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer , 2014, Molecular Cancer.

[2]  C. Ponting,et al.  Evolution and Functions of Long Noncoding RNAs , 2009, Cell.

[3]  M. Toyota,et al.  Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. , 2012, Cancer research.

[4]  Li-tao Yang,et al.  Knockdown of Long Non-coding RNA HOTAIR Suppresses Tumor Invasion and Reverses Epithelial-mesenchymal Transition in Gastric Cancer , 2013, International journal of biological sciences.

[5]  Jing Liu,et al.  The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer , 2013, BMC Cancer.

[6]  Y. Toiyama,et al.  Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. , 2014, Carcinogenesis.

[7]  C. Glass,et al.  The long arm of long noncoding RNAs: roles as sensors regulating gene transcriptional programs. , 2011, Cold Spring Harbor perspectives in biology.

[8]  N. Tanaka,et al.  Enhanced Expression of Long Non-Coding RNA HOTAIR Is Associated with the Development of Gastric Cancer , 2013, PloS one.

[9]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[10]  R. P. Blankfield,et al.  Helicobacter pylori infection and the development of gastric cancer. , 2001, The New England journal of medicine.

[11]  Jia Xu,et al.  HOTAIR Long Noncoding RNA Promotes Gastric Cancer Metastasis through Suppression of Poly r(C)-Binding Protein (PCBP) 1 , 2015, Molecular Cancer Therapeutics.

[12]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[13]  Estradiol induces HOTAIR levels via GPER-mediated miR-148a inhibition in breast cancer , 2015, Journal of Translational Medicine.

[14]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[15]  S. Al-Batran,et al.  Chemotherapy for advanced gastric cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Hui Li,et al.  Long non-coding RNA HOTAIR promotes tumor cell invasion and metastasis by recruiting EZH2 and repressing E-cadherin in oral squamous cell carcinoma. , 2015, International journal of oncology.

[17]  M. Behmanesh,et al.  Up-regulation of HOTAIR long non-coding RNA in human gastric adenocarcinoma tissues , 2013, Medical Oncology.

[18]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[19]  S. Safe,et al.  HOTAIR IS A NEGATIVE PROGNOSTIC FACTOR AND EXHIBITS PRO-ONCOGENIC ACTIVITY IN PANCREATIC CANCER , 2012, Oncogene.

[20]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[21]  R. Kingston,et al.  HOTAIR Lifts Noncoding RNAs to New Levels , 2007, Cell.

[22]  S. Salzberg,et al.  The Transcriptional Landscape of the Mammalian Genome , 2005, Science.

[23]  Sang Kil Lee,et al.  Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma. , 2014, Biochemical and biophysical research communications.

[24]  Yoon-Koo Kang,et al.  Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial , 2010, The Lancet.

[25]  Howard Y. Chang,et al.  Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes , 2010, Science.

[26]  H. Zhang,et al.  PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis. , 2015, Cancer research.

[27]  Jing Jiang,et al.  HOTAIR is a potential target for the treatment of cisplatin‑resistant ovarian cancer. , 2015, Molecular medicine reports.

[28]  P. Stadler,et al.  RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription , 2007, Science.

[29]  B. Su,et al.  Long Noncoding RNA HOTAIR Is Associated with Motility, Invasion, and Metastatic Potential of Metastatic Melanoma , 2013, BioMed research international.

[30]  K. Leslie,et al.  Correlation of MTDH/AEG-1 and HOTAIR Expression with Metastasis and Response to Treatment in Sarcoma Patients. , 2011, Journal of cancer science & therapy.

[31]  Jacques Ferlay,et al.  Recent patterns in gastric cancer: A global overview , 2009, International journal of cancer.

[32]  M. Emadi-Baygi,et al.  Association of HOTAIR expression in gastric carcinoma with invasion and distant metastasis , 2014, Advanced biomedical research.

[33]  Joon-Oh Park,et al.  Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.