Abstract
The research is executed to analyze the connection between genomic instability-associated long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We set a prognostic model up and explored different risk groups' features. The clinical datasets and gene expression profiles of 307 patients have been downloaded from The Cancer Genome Atlas database. We established a prognostic model that combined somatic mutation profiles and lncRNA expression profiles in a tumor genome and identified 35 genomic instability-associated lncRNAs in cervical cancer as a case study. We then stratified patients into low-risk and high-risk groups and were further checked in multiple independent patient cohorts. Patients were separated into two sets: the testing set and the training set. The prognostic model was built using three genomic instability-associated lncRNAs (AC107464.2, MIR100HG, and AP001527.2). Patients in the training set were divided into the high-risk group with shorter overall survival and the low-risk group with longer overall survival (p < 0.001); in the meantime, similar comparable results were found in the testing set (p = 0.046), whole set (p < 0.001). There are also significant differences in patients with histological grades, FIGO stages, and different ages (p < 0.05). The prognostic model focused on genomic instability-associated lncRNAs could predict the prognosis of cervical cancer patients, paving the way for further research into the function and resource of lncRNAs, as well as a key approach to customizing individual care decision-making.
Highlights
The major cause of cancer mortality among women around the globe is cervical cancer (CC) which ranks 4th as a widely diagnosed cancer
The data were collected from The Cancer Genome Atlas (TCGA) database included clinical features, transcriptome profiling data, and somatic mutation information of CC patients. 307 female samples were paired with the Fragments Per Kilobase Million (FPKM) values of long non-coding RNAs (lncRNAs) and mRNA expression profiles, somatic mutation data, and clinical survival data were to further analyze and validate
309 samples (306 tumor and 3 adjacent tissues) from the TCGA database to analyze the differences of gene expression between tumor and adjacent samples, and identified the lncRNAs related to genomic instability in CC patients
Summary
The major cause of cancer mortality among women around the globe is cervical cancer (CC) which ranks 4th as a widely diagnosed cancer. Genomic instability was established by increasing the incidence of gene destruction and genomic integrity loss as a significant feature of tumorigenesis[3]. Genomic instability is correlated and a prognostic factor with tumor development and s urvival[4,5,6]. Though it is uncertain that disrupting the mechanism of genomic stability, numerous studies have confirmed that long noncoding RNA (lncRNA) is functional in such a process[3,7,8,9]. We established a computational model integrating lncRNA expression profiles and somatic mutation profiles in a tumor genome to explore better the dynamic mechanism of lncRNA signature as an indicator of CC genomic stability, and which might help improve its prognostic utility
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