SPRY4-AS1, A Novel Enhancer RNA, Is a Potential Novel Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma

Our plain-English summary of SPRY4-AS1, A Novel Enhancer RNA, Is a Potential Novel Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma, by M. Ye, S. Wang, J.B. Qie, et al (Frontiers in Oncology, 2021).

The study

• Authors: M. Ye, S. Wang, J.B. Qie, P.L. Sun
• Journal: Frontiers in Oncology
• Published: 2021;11:765484
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A growing number of evidence have demonstrated the involvement of enhancer RNAs (eRNAs) in tumor progression. However, the possible functions of eRNAs in hepatocellular carcinoma (HCC) remain largely unclear. Our present research aimed to screen critical eRNAs and to further delve into the clinical significance of eRNAs in HCC patients. In this study, we identified 124 prognosis-related eRNAs by analyzing The Cancer Genome Atlas (TCGA) datasets. Among them, SPRY4 antisense RNA 1 (SPRY4-AS1) may be a key eRNA involved in HCC progression. SPRY4 was a regulatory target of SPRY4-AS1. High SPRY4-AS1 expression was associated with poor prognosis of HCC patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) assays revealed that the mainly enriched biological process included Human papillomavirus infection, Hippo signaling pathway, and Proteoglycans in cancer. Besides, RT-PCR and immunohistochemical staining confirmed SPRY4-AS1 as an overexpressed eRNA in HCC specimens. The pan-cancer assays revealed that SPRY4-AS1 was associated with glioblastoma multiforme (GBM), adrenocortical carcinoma (ACC), brain lower grade glioma (LGG) and mesothelioma(MESO). Positive associations were observed between SPRY4-AS1 and SPRY4 (its target gene) in 16 tumor types. Collectively, our findings reveal a novel eRNA SPRY4-AS1 for HCC progression and suggest that SPRY4-AS1 may be a potential biomarker and therapeutic target for HCC.

Copyright © 2021 Ye, Wang, Qie and Sun.

In plain English

This study was about hepatocellular carcinoma, a type of liver cancer, not about asbestos. The authors analyzed public data from The Cancer Genome Atlas on 371 liver cancer cases to find enhancer RNAs (RNA that does not make protein) linked to survival. They found 124 such RNAs and singled out one, SPRY4-AS1. Patients with higher SPRY4-AS1 levels had shorter overall survival (p = 0.0002), and SPRY4-AS1 levels rose with those of its target gene, SPRY4 (R = 0.56). Its levels differed by sex, tumor grade, stage and cancer status, but not by age. In tumor and matched normal tissue from 10 patients at Jinshan Hospital, Fudan University, SPRY4-AS1 and SPRY4 were higher in tumors. Across other cancer types, SPRY4-AS1 was associated with survival in four, including mesothelioma. The supplied text gives no mesothelioma direction, numbers or site, and its survival curve (Figure 5D) was not reproduced. The authors concluded that SPRY4-AS1 may be a novel prognostic biomarker for liver cancer patients. They noted that the model relied on TCGA data and that the mechanism was not shown.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatics analysis of public cancer database (TCGA) data, with laboratory confirmation (RT-qPCR and immunohistochemistry) in 10 paired patient tissue samples
• Who was studied: 371 hepatocellular carcinoma cases from The Cancer Genome Atlas. Also 10 paired tumor and matched non-tumor specimens from 10 HCC patients aged 27 to 78 at Jinshan Hospital, Fudan University, Shanghai, collected June 2020 to May 2021. A pan-cancer check used TCGA data on other tumor types, including mesothelioma (MESO).
• Exposure: No asbestos or other environmental or occupational exposure was studied. The factor examined was the level of the RNA SPRY4-AS1 (and its target gene SPRY4) in tumor tissue, split into high and low groups at the median.
• Main results:
  • In the TCGA hepatocellular carcinoma data, 124 enhancer RNAs were associated with prognosis (p < 0.05).
  • HCC patients with high SPRY4-AS1 expression had shorter overall survival than the low-expression group (p = 0.0002).
  • In TCGA HCC data, SPRY4 expression was positively correlated with SPRY4-AS1 (R = 0.56).
  • In HCC patients, SPRY4-AS1 expression was not associated with age (p = 0.079). It was linked to gender (p = 0.00016), grade, stage and cancer status (p = 0.0039), and was higher in female than in male patients.
  • In 10 HCC specimens compared with 10 non-tumor specimens, RT-PCR showed increased SPRY4-AS1 and SPRY4 expression in the tumors. Immunohistochemistry showed lower SPRY4 protein in non-tumor than in tumor specimens.
  • KEGG pathway analysis of genes linked to SPRY4-AS1 mainly involved Human papillomavirus infection, Hippo signaling pathway, and Proteoglycans in cancer (adjusted p < 0.001).
  • In the pan-cancer analysis, SPRY4-AS1 was associated with survival in adrenocortical carcinoma (ACC), glioblastoma multiforme (GBM), brain lower grade glioma (LGG) and mesothelioma (MESO). The supplied text gives no numbers, direction or mesothelioma site. The survival curves in Figure 5 were not reproduced in the text. SPRY4-AS1 and SPRY4 were associated in 16 tumor types.
• The authors' conclusion: The authors concluded that SPRY4-AS1 may be a novel prognostic biomarker for HCC patients. They said the results may help prognostic evaluation of HCC and guide further study of targeted therapies.
• Limitations the authors state:
  • The predictive model was based on TCGA data, so it is unknown whether SPRY4-AS1 has similar predictive power in HCC patients at other Chinese hospitals.
  • The authors did not identify the molecular pathway through which SPRY4-AS1 acts.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Carcinoma, Prognosis, Hippo Signaling Pathway, Immunohistochemistry, Mesothelioma.

Related studies

• The "don't eat me" signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma — C.M. Schürch, S. Forster, et al. (2017)
• Identification of Novel Biomarkers and Potential Therapeutic Targets for Systemic Sclerosis: An Integrated Analysis of Plasma Proteome-Wide Mendelian Randomization and Transcriptome — H. Li, Q. Li, et al. (2025)
• Pan-cancer analyses of bromodomain containing 9 as a novel therapeutic target reveals its diagnostic, prognostic potential and biological mechanism in human tumours — Y. Chen, Z. Gao, et al. (2024)
• Xanthine dehydrogenase as a prognostic biomarker related to tumor immunology in hepatocellular carcinoma — Z. Lin, Y.Z. Xie, et al. (2021)
• FASN for diffuse malignant peritoneal mesothelioma: a prognostic biomarker after CRS+HIPEC and a therapeutic target — V. Doldi, C.M. Ciniselli, et al. (2026)
• HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma — Y. Wang, Z. Jiang, et al. (2019)

Browse more research in Frontiers in Oncology, or return to medical research.