Evidence suggests that the long non-coding RNA (lncRNA), HOTAIR, is involved in cervical cancer pathogenesis. We examined serum HOTAIR expression levels in cervical cancer patients and determined the relationships between HOTAIR expression and several clinicopathological factors, including survival. We also examined the functional consequences of HOTAIR overexpression both in vitro and in vivo. Compared with control patients, HOTAIR expression was significantly greater in the serum of cervical cancer patients (P < 0.001). The results indicated that this increase was significantly associated with tumour size (P = 0.030), lymphovascular space invasion (P = 0.037), and lymph node metastasis (P = 0.043). Univariate analysis revealed that disease-free survival and overall survival times were significantly shorter in cervical cancer patients with high HOTAIR expression (hazard ratio [HR] = 4.27, 4.68 and P = 0.039, 0.031, respectively). Cell proliferation and invasion in vitro increased as a result of lentiviral-mediated HOTAIR overexpression in cervical cancer cell lines. HOTAIR knockdown inhibited these properties and increased apoptosis. In vivo xenograft experiments using the HOTAIR-overexpressing SiHa cell line revealed that HOTAIR was a strong inducer of tumour growth and modulated the expression of epithelial-mesenchymal transition and Notch-Wnt signalling pathway-related genes. This result suggested that HOTAIR overexpression promoted cell proliferation and invasion. In conclusion, increased HOTAIR expression was associated with decreased patient survival times. HOTAIR may be a useful target for treatment of cervical cancer patients.

Purpose Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. Materials and Methods To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). Results Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25 , HLA-DPA1 , AKT3 , and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). Conclusion We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

PurposeAlthough the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients. Materials and MethodsEighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity.ResultsXenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers.ConclusionsTumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

Long noncoding RNAs (lncRNAs) are involved in developmental processes and diseases and function as critical regulators of a number of different cancer types. Previous research has revealed that lncRNAs affect cervical cancer development. Steroid receptor activator (), an lncRNA, serves as a critical regulator of gynecologic cancer. However, the association between expression and cervical cancer remains unclear. In the present study, the expression levels in patients with cervical cancer were examined and the association between expression and clinicopathological factors was determined. expression was observed in cervical cancer tissues (n=100) and corresponding normal tissues (n=22) using reverse transcription-quantitative polymerase chain reaction, and its associations with clinical parameters and prognosis were analyzed. expression was significantly greater in tissues from patients with cervical cancer compared with in control patients (P<0.001). Multivariate analysis revealed that high expression was an independent prognostic factor of overall survival (hazard ratio=3.714, P=0.031). The present study additionally investigated the biofunctional consequences of overexpression using Cell Counting kit-8, wound healing migration and Matrigel invasion assays. The results demonstrated that overexpression enhanced cell proliferation, migration and invasion . Furthermore, overexpression induced the epithelial-mesenchymal transition (EMT). Therefore, may promote tumor aggressiveness through the upregulation of EMT-associated genes. These results indicated that may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervical cancer.