Abstract

Enhancer RNA is a kind of non-coding RNA, which is transcribed from the enhancer region of gene and plays an important role in gene transcription regulation. However, the role of eRNA in pancreatic adenocarcinoma (PAAD) is still unclear. In this study, we identified the key eRNA and its target gene in PAAD. The transcriptome data and clinical information of pancreatic cancer were downloaded from the UCSC Xena platform. A total of 2,695 eRNAs and its target gene predicted by the PreSTIGE method were selected as candidate eRNA–target pairs. After survival analysis, we found that LINC00242 was the eRNA most related to patients’ survival, and correlation analysis further indicated that LINC00242 and its target gene PHF10 had a significant co-expression relationship. Downregulation of LINC00242 was significantly associated with unfavorable clinicopathological features. Based on pan-cancer analysis, we found that LINC00242 was associated with the survival of multiple cancers, and LINC00242 was co-expressed with its target genes in multiple cancer types. External experiments further demonstrated that PHF10 was the downstream target gene of LINC00242. After ssGSEA analysis, PAAD patients were classified as high, medium, and low immune cell infiltration clusters. Compared with the low and medium immune infiltration clusters, the expression level of PHF10 was significantly upregulated in the high immune infiltration clusters. After performing the CIBERSORT algorithm, we found that there was a significant difference in the abundance of immune infiltrating cells between the PHF10 high- and low-expression groups. Additionally, the web tool TIMER was used to detect the distribution and expression of PHF10 in pan-cancer.

Highlights

  • According to reports, pancreatic adenocarcinoma ranks fourth in cancer-related deaths, with a 5-year survival rate of approximately 9% [1]

  • According to gene expression profile and clinical information from 177 pancreatic adenocarcinoma (PAAD) patients, we identified 15 of the 1,559 candidate enhancer RNA (eRNA), which were significantly correlated with patients’ overall survival (OS) (Kaplan–Meier, p < 0.01; Supplementary Table 2)

  • Pancreatic cancer has a high morbidity and mortality across the world, and the treatment of PAAD still remains a challenge for human beings

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Summary

Introduction

Pancreatic adenocarcinoma ranks fourth in cancer-related deaths, with a 5-year survival rate of approximately 9% [1]. Pancreatic adenocarcinoma tends to be asymptomatic in its early stages, and most patients with PAAD are not suitable for surgical treatment when they are diagnosed in the late stage [2]. Studies have confirmed that several treatment methods including immunotherapy [3, 4] and targeted therapy [5, 6] can improve the survival rate of PAAD patients, but the effect is still limited. This may be related to the different sensitivity caused by the complexity and heterogeneity of tumor tissue. There is an urgent need to find biomarkers related to the prognosis of PAAD and to predict the sensitivity of immunotherapy and targeted therapy

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