Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Esophageal Cancer | Research

High expression of HNRNPR in ESCA combined with 18F-FDG PET/CT metabolic parameters are novel biomarkers for preoperative diagnosis of ESCA

Authors: Xiao-Yu Liu, Yan Gao, Xue-Yan Kui, Xu-Sheng Liu, Yao-hua Zhang, Yu Zhang, Chang-Bin Ke, Zhi-Jun Pei

Published in: Journal of Translational Medicine | Issue 1/2022

Login to get access

Abstract

Background

The aim of this study was to determine the expression and function of heterogeneous nuclear ribonucleoprotein R (HNRNPR) in esophageal carcinoma (ESCA), the correlation between its expression and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerized tomography scan (PET/CT)-related parameters. We also investigated whether 18F-FDG PET/CT can be used to predict the expression of HNRNPR in ESCA.

Methods

We analyzed patients with ESCA who underwent 18F-FDG PET/CT before surgery, and their tissues were stained with HNRNPR IHC. The associated parameters were derived using the 18F-FDG PET imaging data, and the correlation with the IHC score was evaluated. The Oncomine, TCGA, and GEO datasets were used to investigate HNRNPR expression in the pan- and esophageal cancers, as well as its relationship with N6-methyladenosine (m6A) modification and glycolysis. The R software, LinkedOmics, GeneMANIA, and StringOnline tools were used to perform GO/KEGG, GGI, and PPI analyses on the HNRNPR.

Results

HNRNPR is highly expressed in the majority of pan-cancers, including ESCA, and is associated with BMI, weight, and history of reflux in patients with ESCA. HNRNPR is somewhat accurate in predicting the clinical prognosis of ESCA. HNRNPR expression was positively correlated with SUVmax, SUVmean, and TLG in ESCA (p < 0.05). The combination of these three variables provides a strong predictive value for HNRNPR expression in ESCA. GO/KEGG analysis showed that HNRNPR played a role in the regulation of cell cycle, DNA replication, and the Fannie anemia pathway. The analysis of the TCGA and GEO data sets revealed a significant correlation between HNRNPR expression and m6A and glycolysis-related genes. GSEA analysis revealed that HNRNPR was involved in various m6A and glycolysis related-pathways.

Conclusion

HNRNPR overexpression correlates with 18F-FDG uptake in ESCA and may be involved in the regulation of the cell cycle, m6A modification, and cell glycolysis. 18F-FDG PET/CT-related parameters can predict the diagnostic accuracy of HNRNPR expression in ESCA.
Literature
1.
Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.PubMedCrossRef
2.
Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed
3.
Lu Y, Guo L, Ding G. PD1+ tumor associated macrophages predict poor prognosis of locally advanced esophageal squamous cell carcinoma. Future Oncol. 2019;15(35):4019–30.PubMedCrossRef
4.
Chen Y, et al. The clinical outcomes of locally advanced cervical esophageal squamous cell carcinoma patients receiving curative concurrent chemoradiotherapy: a population-based propensity score-matched analysis. Cancers. 2019;11(4):451.PubMedCentralCrossRef
5.
Liu X, et al. Overexpression of METTL3 associated with the metabolic status on 18F-FDG PET/CT in patients with esophageal carcinoma. J Cancer. 2020;11(16):4851–60.PubMedPubMedCentralCrossRef
6.
Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50.PubMedCrossRef
7.
Ott K, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2006;24(29):4692–8.PubMedCrossRef
8.
Nair VS, et al. Prognostic PET 18F-FDG uptake imaging features are associated with major oncogenomic alterations in patients with resected non-small cell lung cancer. Can Res. 2012;72(15):3725–34.CrossRef
9.
Kawada K, et al. Relationship between18F-fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer. Clin Cancer Res. 2012;18(6):1696–703.PubMedCrossRef
10.
Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11(5):325–37.PubMedCrossRef
11.
Wang S, et al. Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expression. Mol Cancer. 2019;18(1):145.PubMedPubMedCentralCrossRef
12.
Mathupala SP, Ko YH, Pedersen PL. Hexokinase-2 bound to mitochondria: cancer’s stygian link to the “Warburg effect” and a pivotal target for effective therapy. Semin Cancer Biol. 2009;19(1):17–24.PubMedCrossRef
13.
Levine EA, et al. Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer. Ann Surg. 2006;243(4):472–8.PubMedPubMedCentralCrossRef
14.
Blackstock AW, et al. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer. Int J Radiat Oncol Biol Phys. 2006;64(2):455–60.PubMedCrossRef
15.
Monjazeb AM, et al. Outcomes of patients with esophageal cancer staged with [(1)(8)F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection? J Clin Oncol. 2010;28(31):4714–21.PubMedPubMedCentralCrossRef
16.
Goodman KA, et al. Randomized phase II study of PET response-adapted combined modality therapy for esophageal cancer: mature results of the CALGB 80803 (Alliance) trial. J Clin Oncol. 2021;39(25):2803–15.PubMedPubMedCentralCrossRef
17.
Choi YD, et al. Heterogeneous nuclear ribonucleoproteins: role in RNA splicing. Science. 1986;231(4745):1534–9.PubMedCrossRef
18.
Duijkers FA, et al. HNRNPR variants that impair homeobox gene expression drive developmental disorders in humans. Am J Hum Genet. 2019;104(6):1040–59.PubMedPubMedCentralCrossRef
19.
Ghanawi H, et al. Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin. Nucleic Acids Res. 2021;49(21):12284–305.PubMedPubMedCentralCrossRef
20.
21.
22.
23.
Fabbri L, et al. The plasticity of mRNA translation during cancer progression and therapy resistance. Nat Rev Cancer. 2021;21(9):558–77.PubMedCrossRef
24.
Rapino F, et al. Codon-specific translation reprogramming promotes resistance to targeted therapy. Nature. 2018;558(7711):605–9.PubMedCrossRef
25.
26.
Pinol-Roma S, Dreyfuss G. hnRNP proteins: localization and transport between the nucleus and the cytoplasm. Trends Cell Biol. 1993;3(5):151–5.PubMedCrossRef
27.
Han J, et al. Lysine-specific histone demethylase 1 promotes oncogenesis of the esophageal squamous cell carcinoma by upregulating DUSP4. Biochemistry. 2021;86(12):1624–34.PubMed
28.
Wang Y, et al. Sam68 promotes cellular proliferation and predicts poor prognosis in esophageal squamous cell carcinoma. Tumour Biol. 2015;36(11):8735–45.PubMedCrossRef
29.
30.
Beyer AL, et al. Identification and characterization of the packaging proteins of core 40S hnRNP particles. Cell. 1977;11(1):127–38.PubMedCrossRef
31.
Chaudhury A, Chander P, Howe PH. Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: focus on hnRNP E1’s multifunctional regulatory roles. RNA. 2010;16(8):1449–62.PubMedPubMedCentralCrossRef
32.
33.
Phoomak C, et al. O-GlcNAc-induced nuclear translocation of hnRNP-K is associated with progression and metastasis of cholangiocarcinoma. Mol Oncol. 2019;13(2):338–57.PubMedPubMedCentralCrossRef
34.
Zhang L, et al. Nujiangexathone A, a novel compound from Garcinia nujiangensis, suppresses cervical cancer growth by targeting hnRNPK. Cancer Lett. 2016;380(2):447–56.PubMedCrossRef
35.
36.
Zhou ZJ, et al. Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma. Int J Cancer. 2013;132(5):1080–9.PubMedCrossRef
37.
Zhou ZJ, et al. HNRNPAB induces epithelial-mesenchymal transition and promotes metastasis of hepatocellular carcinoma by transcriptionally activating SNAIL. Cancer Res. 2014;74(10):2750–62.PubMedCrossRef
38.
Briese M, et al. hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons. Proc Natl Acad Sci U S A. 2018;115(12):E2859–68.PubMedPubMedCentralCrossRef
39.
40.
Rodrigues C, Pires D, Ascher DB. mmCSM-PPI: predicting the effects of multiple point mutations on protein-protein interactions. Nucleic Acids Res. 2021;49(W1):W417–24.PubMedPubMedCentralCrossRef
41.
Zang B, et al. Metabolomic characterization reveals ILF2 and ILF3 affected metabolic adaptions in esophageal squamous cell carcinoma. Front Mol Biosci. 2021;8: 721990.PubMedPubMedCentralCrossRef
42.
43.
44.
Chaudhary S, et al. Sox2: a regulatory factor in tumorigenesis and metastasis. Curr Protein Pept Sci. 2019;20(6):495–504.PubMedCrossRef
45.
46.
Saigusa S, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol. 2009;16(12):3488–98.PubMedCrossRef
47.
Li Z, et al. FTO plays an oncogenic role in acute myeloid leukemia as a N(6)-methyladenosine RNA demethylase. Cancer Cell. 2017;31(1):127–41.PubMedCrossRef
48.
Song Y, et al. RBMX contributes to hepatocellular carcinoma progression and sorafenib resistance by specifically binding and stabilizing BLACAT1. Am J Cancer Res. 2020;10(11):3644–65.PubMedPubMedCentral
49.
Shen D, et al. METTL14-mediated Lnc-LSG1 m6A modification inhibits clear cell renal cell carcinoma metastasis via regulating ESRP2 ubiquitination. Mol Ther Nucleic Acids. 2022;27:547–61.PubMedCrossRef
50.
Dong L, et al. The loss of RNA N(6)-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8(+) T cell dysfunction and tumor growth. Cancer Cell. 2021;39(7):945-957.e10.PubMedCrossRef
51.
52.
53.
54.
55.
Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 2018;154(2):360–73.PubMedCrossRef
56.
Lahmann PH, et al. Body mass index, long-term weight change, and esophageal squamous cell carcinoma: is the inverse association modified by smoking status? Cancer. 2012;118(7):1901–9.PubMedCrossRef
57.
Rosenberg PS, Alter BP, Ebell W. Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry. Haematologica. 2008;93(4):511–7.PubMedCrossRef
58.
Arnett A, et al. Utility of (18)F-FDG PET for predicting histopathologic response in esophageal carcinoma following chemoradiation. J Thorac Oncol. 2017;12(1):121–8.PubMedCrossRef
59.
Cuellar SLB, et al. Clinical staging of patients with early esophageal adenocarcinoma: does FDG-PET/CT have a role? J Thorac Oncol. 2014;9(8):1202–6.PubMedCrossRef
Metadata
Title
High expression of HNRNPR in ESCA combined with 18F-FDG PET/CT metabolic parameters are novel biomarkers for preoperative diagnosis of ESCA
Authors
Xiao-Yu Liu
Yan Gao
Xue-Yan Kui
Xu-Sheng Liu
Yao-hua Zhang
Yu Zhang
Chang-Bin Ke
Zhi-Jun Pei
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03665-4

Other articles of this Issue 1/2022

Journal of Translational Medicine 1/2022 Go to the issue

Letter to the Editor

Targeting ERβ to fight melanoma: a new valid approach?

Research

Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment

Methodology

HiTIMED: hierarchical tumor immune microenvironment epigenetic deconvolution for accurate cell type resolution in the tumor microenvironment using tumor-type-specific DNA methylation data

Research

Polygenic risk of paclitaxel-induced peripheral neuropathy: a genome-wide association study

Research

Lenvatinib inhibits the growth of gastric cancer patient-derived xenografts generated from a heterogeneous population

Research

Dyslipidemia induced large-scale network connectivity abnormality facilitates cognitive decline in the Alzheimer’s disease
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits