Evidence map›Paper›PMID 30819181›Full record

ArticleJournal of translational medicine2019

Bioinformatics-based discovery of the urinary BBOX1 mRNA as a potential biomarker of diabetic kidney disease.

Le-Ting Zhou, Lin-Li Lv, Shen Qiu, Qing Yin, Zuo-Lin Li, Tao-Tao Tang, Li-Hua Ni, Ye Feng, Bin Wang, Kun-Ling Ma and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
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  4. Integrated multiomic analyses: An approach to improve understanding of diabetic kidney disease.Diabetic medicine : a journal of the British Diabetic Association · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Le-Ting ZhouInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Lin-Li LvInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Shen QiuInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Qing YinInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Zuo-Lin LiInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Tao-Tao TangInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Li-Hua NiInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Ye FengInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Bin WangInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Kun-Ling MaInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China.
Bi-Cheng LiuInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, No. 87 Dingjiaqiao Rd, Nanjing, Jiangsu, China. liubc64@163.com.
Zhongda Hospital Southeast University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the world. Emerging evidence has shown that urinary mRNAs may serve as early diagnostic and prognostic biomarkers of DKD. In this article, we aimed to first establish a novel bioinformatics-based methodology for analyzing the "urinary kidney-specific mRNAs" and verify their potential clinical utility in DKD.

methodsTo select candidate mRNAs, a total of 127 Affymetrix microarray datasets of diabetic kidney tissues and other tissues from humans were compiled and analyzed using an integrative bioinformatics approach. Then, the urinary expression of candidate mRNAs in stage 1 study (n = 82) was verified, and the one with best performance moved on to stage 2 study (n = 80) for validation. To avoid potential detection bias, a one-step Taqman PCR assay was developed for quantification of the interested mRNA in stage 2 study. Lastly, the in situ expression of the selected mRNA was further confirmed using fluorescent in situ hybridization (FISH) assay and bioinformatics analysis.

resultsOur bioinformatics analysis identified sixteen mRNAs as candidates, of which urinary BBOX1 (uBBOX1) levels were significantly upregulated in the urine of patients with DKD. The expression of uBBOX1 was also increased in normoalbuminuric diabetes subjects, while remained unchanged in patients with urinary tract infection or bladder cancer. Besides, uBBOX1 levels correlated with glycemic control, albuminuria and urinary tubular injury marker levels. Similar results were obtained in stage 2 study. FISH assay further demonstrated that BBOX1 mRNA was predominantly located in renal tubular epithelial cells, while its expression in podocytes and urothelium was weak. Further bioinformatics analysis also suggested that tubular BBOX1 mRNA expression was quite stable in various types of kidney diseases.

conclusionsOur study provided a novel methodology to identify and analyze urinary kidney-specific mRNAs. uBBOX1 might serve as a promising biomarker of DKD. The performance of the selected urinary mRNAs in monitoring disease progression needs further validation.

Indexed as

Computational BiologyBiomarkersDatabases, GeneticDiabetic NephropathiesFemalegamma-Butyrobetaine DioxygenaseHumansKidneyMaleMiddle AgedReproducibility of ResultsRNA, MessengerUp-RegulationBBOX1 protein, humanBiomarkersgamma-Butyrobetaine DioxygenaseRNA, MessengerBioinformaticsBiomarkerDiabetic kidney diseaseMicroarrayUrinary mRNA

Identifiers

PMID30819181
PMCPMC6394064
OpenAlexW2938801144

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.