Association of LINC00858 with clinical outcome of patients with cervical cancer who received standard concurrent chemo-radiotherapy.

Abstract

e18002 Background: Cervical cancer is the second most common malignant tumour threatening women’s health and remains a vast challenge for many underdeveloped nations. Combination of concurrent chemotherapy with external beam radiation therapy (EBRT) followed by intracavitary brachytherapy (ICBT) boost achieved a favorable outcome for cervical cancer patients. However, the reduced sensitivity of cancer cells to radiotherapy is an important cause of re-currence and metastasis in some patients, it is necessary to constantly improve the radiotherapy technology and the treatment effect. Long noncoding RNAs (lncRNA) are noncoding RNA molecules greater than 200 nucleotides in size that are often critical regulators of gene expression, lncRNAs were implicated in stem cell pluripotency by examining the expression. Methods: Whole-exome sequencing and RNA sequencing were conducted in patients with locally advanced cervical cancer (LACC) to identify prognostic variants by using a two-stage case-control design. Patients developed local recurrences in 3 years after standard concurrent chemotherapy with EBRT followed by ICBT were divided in case group. While patients did not show local recurrences were regarded as a radio-sensitive group. In the first stage, DNA and RNA were extracted from formalin-fixed paraffin-embedded tumor tissues of 32 patients. In the second stage, to validate the significant association between LincRNA and Local control rate of patients found in first stage, RT-PCR was carried out in RNA samples from an independent 100 patients (with same criteria of selection). Cox regression models were used to analyze the association between genetic variants and time-to-event outcomes. Results: In the first stage, expression of 7 LincRNAs: RP11-335O4.(P = 0.01,HR = 10.86), CTD-2292M14.1(P = 0.01,HR = 9.47),RP11-94H6.1(P = 0.02,HR = 9.47), RP11-417L19.2(P = 0.0,HR = 9.36), RP4-683M8.2(P = 0.02,HR = 10.82), RP11-20B24.3(P = 0.02,HR = 8.90) and LINC00858(P = 0.03,HR = 6.41) were found to be markedly correlated with relapse-free survival in 32 patients. Among these LincRNAs, LINC00858 (P = 0.01, HR = 11.23) remained significant association with relapse-free survival in 100 independent patients. Conclusions: Our data suggest that LincRNA may be a useful predict marker for radiosencetivity of cervical cancer patients.