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Identifying critical protein-coding genes and long non-coding RNAs in non-functioning pituitary adenoma recurrence.

ABSTRACT: Non-functioning pituitary adenoma (NFPA) is a very common type of intracranial tumor. Monitoring and predicting the postoperative recurrence of NFPAs is difficult, as these adenomas do not present with serum hormone hypersecretion. Long non-coding RNAs (lncRNAs) and protein-coding genes (PCGs) play critical roles in the development and progression of numerous tumors. However, the complex network of RNA interactions related to the mechanisms underlying the postoperative recurrence of NFPA is still unclear. In the present study, 73 patients with NFPA were investigated using high-throughput sequencing and follow-up investigations. In total, 6 of these patients with recurrence within 1 year after surgery were selected as the fast recurrence group, and 6 patients with recurrence 5 years after surgery were selected as the slow recurrence group. By performing differential expression analysis of the fast recurrence and slow recurrence groups, a set of differentially expressed PCGs and lncRNAs were obtained (t-test, P<0.05). Next, protein-protein interaction coregulatory networks and lncRNA-mRNA coexpression networks were identified. In addition, the hub lncRNA-mRNA modules related to NFPA recurrence were further screened and transcriptome expression markers for NFPA regression were identified (log-rank test, P<0.05). Finally, the ability of the hub and module genes to predict recurrence and progression-free survival in patients with NFPA was evaluated. To confirm the credibility of the bioinformatic analyses, nucleolar protein 6 and LL21NC02-21A1.1 were randomly selected from among the genes with prognostic significance for validation by reverse transcription-quantitative PCR in another set of NFPA samples (n=9). These results may be helpful for evaluating the slow and rapid recurrence of NFPA after surgery and exploring the mechanisms underlying NFPA recurrence. Future effective biomarkers and therapeutic targets may also be revealed.

SUBMITTER: Guo J

PROVIDER: S-EPMC7882882 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Identifying critical protein-coding genes and long non-coding RNAs in non-functioning pituitary adenoma recurrence.

Guo Jing J Fang Qiuyue Q Liu Yulou Y Xie Weiyan W Zhang Yazhuo Y Li Chuzhong C

Oncology letters 20210208 4

Non-functioning pituitary adenoma (NFPA) is a very common type of intracranial tumor. Monitoring and predicting the postoperative recurrence of NFPAs is difficult, as these adenomas do not present with serum hormone hypersecretion. Long non-coding RNAs (lncRNAs) and protein-coding genes (PCGs) play critical roles in the development and progression of numerous tumors. However, the complex network of RNA interactions related to the mechanisms underlying the postoperative recurrence of NFPA is stil ...[more]

PMID: 33664827

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Project description:PurposeNon-functioning pituitary adenoma (NFPA) is a very common type of intracranial tumor, which can be locally invasive and can have a high recurrence rate. The tumor microenvironment (TME) shows a high correlation with tumor pathogenesis and prognosis. The current study aimed to identify microenvironment-related genes in NFPAs and assess their prognostic value.Methods73 NFPA tumor samples were collected from Beijing Tiantan Hospital and transcriptional expression profiles were obtained through microarray analysis. The immune and stromal scores of each sample were calculated through the ESTIMATE algorithm, and the patients were divided into high and low immune/stromal score groups. Intersection differentially expressed genes (DEGs) were then obtained to construct a protein-protein interaction (PPI) network. Potential functions and pathways of intersection DEGs were then analyzed through Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The prognostic value of these genes was evaluated. The quantitative real-time polymerase chain reaction in another set of NFPA samples was used to confirm the credibility of the bioinformatics analysis.ResultsThe immune/stromal scores were significantly correlated with cavernous sinus (CS) invasion. The Kaplan-Meier curve indicated that the high immune score group was significantly related to poor recurrence-free survival. We identified 497 intersection DEGs based on the high vs. low immune/stromal score groups. Function enrichment analyses of 497 DEGs and hub genes from the PPI network showed that these genes are mainly involved in the immune/inflammatory response, T cell activation, and the phosphatidylinositol 3 kinase-protein kinase B signaling pathway. Among the intersection DEGs, 88 genes were further verified as significantly expressed between the CS invasive group and the non-invasive group, and five genes were highly associated with NFPA prognosis.ConclusionWe screened out a series of critical genes associated with the TME in NFPAs. These genes may play a fundamental role in the development and prognosis of NFPA and may yield new therapeutic targets.

Dataset Information

Identifying critical protein-coding genes and long non-coding RNAs in non-functioning pituitary adenoma recurrence.

Publications

Identifying critical protein-coding genes and long non-coding RNAs in non-functioning pituitary adenoma recurrence.

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