Abstract 210: Integrated analysis of differential expressed genes and somatic variants in transcriptomic data of prostate cancer patients reveals potential diagnostic and prognostic markers

Abstract

Abstract Background: Despite recent advances in the diagnosis and treatment of prostate cancer, the overall prognosis and survival rates for prostate cancer remains low. With the recent advances in next-generation sequencing technologies, researchers have made use of whole genome sequencing to identify genetic variants or RNA sequencing to find differentially expressed genes (DEGs). Given the situation that researchers seldom combine variants and DEG information from transcriptomic data, we hypothesized that systematically integrating the analysis of DEGs and somatic mutations may reveal novel and promising markers for diagnosis and prognosis in prostate cancer. Materials and Methods: To tackle this question, we analyzed 60 pairs of transcriptomic data from prostate cancer patients by a bioinformatics pipeline integrating HISAT 2/StringTie/DESeq 2 and GATK/SIFT4G. The data called by the pipeline were further validated in public datasets from TCGA and GTEx by GEPIA. Results: Totally, 1417 intolerant genes were called by the combination of GATK and SIFT after deducting 891 overlap intolerant genes between prostate cancer and adjacent normal groups. At the same time, 73 DEGs were elucidated by HISAT 2/StringTie/DESeq 2 pipeline. By integrating results of 73 DEGs and 1417 somatic mutations, novel candidate markers NOC2L and GPRASP1 were identified. Using the public datasets from TCGA and GTEx with 492 prostate cancer samples and 152 normal prostate tissue samples for validation by GEPIA, the expression level of NOC2L was found to be significantly higher in prostate cancer compared with the paired normal samples while the expression level of GPRASP1 is significantly lower in prostate cancer compared with the paired normal samples. NOC2L, which can act as a transcription corepressor of p53/TP53- and TP63-mediated transactivation of the p21/CDKN1A promoter, may be involved in the regulation of p53/TP53-dependent apoptosis. GPRASP1, which is a tumor suppressor, has been reported to have differential methylation in prostate cancer. Moreover, NOC2L was identified as a prognostic marker of prostate cancer patients. A higher expression of NOC2L was significantly correlated with the worse diseasefree survival with a hazard ratio of 1.8, which was confirmed by a TCGA dataset with 344 prostate cancer patients. Conclusion: Our study identified novel candidate markers NOC2L and GPRASP1 for prostate cancer by integrated analysis of DEGs and somatic variants in transcriptomic data. These markers were further validated in public datasets from TCGA and GTEx. Our findings can shed light on the better diagnosis and prognosis in prostate cancer. Citation Format: Yonghao LIANG, Stephen Kwok-Wing Tsui. Integrated analysis of differential expressed genes and somatic variants in transcriptomic data of prostate cancer patients reveals potential diagnostic and prognostic markers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 210.