Evidence map›Paper›PMID 37684587›Full record

ArticleBMC cancer2023

Altered expression of the L-arginine/nitric oxide pathway in ovarian cancer: metabolic biomarkers and biological implications.

Linfeng Chen, Qiming Tang, Keying Zhang, Qianyang Huang, Yun Ding, Bo Jin, Szumam Liu, KuoYuan Hwa, C James Chou, Yani Zhang and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Review
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  5. Article
  6. Review
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

26 authors.

Linfeng Chen *Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Qiming Tang *Shanghai Yunxiang Medical Technology Co., Ltd., Shanghai, China.
Keying Zhang *Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.
Qianyang Huang *mProbe Inc, Palo Alto, CA, USA.
Yun DingmProbe Inc, Palo Alto, CA, USA.
Bo JinTianjin Yunjian Medical Laboratory Institute Co., Ltd, Tianjin, China.
Szumam LiuSchool of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
KuoYuan HwamProbe Inc, Palo Alto, CA, USA.
C James ChouSchool of Medicine, Stanford University, Stanford, CA, USA.
Yani ZhangTianjin Yunjian Medical Laboratory Institute Co., Ltd, Tianjin, China.
Sheeno ThyparambilmProbe Inc, Palo Alto, CA, USA.
Weili LiaomProbe Inc, Palo Alto, CA, USA.
Zhi HanSchool of Medicine, Stanford University, Stanford, CA, USA.
Richard MortensenmProbe Inc, Palo Alto, CA, USA.
James SchillingmProbe Inc, Palo Alto, CA, USA.
Zhen LiShanghai Yunxiang Medical Technology Co., Ltd., Shanghai, China.
Robert HeatonmProbe Inc, Palo Alto, CA, USA.
Lu TianSchool of Medicine, Stanford University, Stanford, CA, USA.
Harvey J CohenSchool of Medicine, Stanford University, Stanford, CA, USA.
Karl G SylvesterSchool of Medicine, Stanford University, Stanford, CA, USA.
Rebecca C ArentSchool of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Xinyang ZhaoSchool of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Doff B McElhinneySchool of Medicine, Stanford University, Stanford, CA, USA.
Yumei WuBeijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China. wym597118@ccmu.edu.cn.
Wenpei BaiBeijing Shijitan Hospital, Capital Medical University, Beijing, China. baiwp@bjsjth.cn.
Xuefeng B LingSchool of Medicine, Stanford University, Stanford, CA, USA. bxling@stanford.edu.

Funding

Beijing Shijitan Hospital, Capital Medical University, Open Research Funding of Laboratory of central laboratory 2019KF26Science and Technology Commission of Shanghai Municipality 18401933401
6 · The paper itself

Abstract

motivationOvarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer.

methodsA functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort. This cohort consisted of control samples (n = 79), stage I/II samples (n = 280), and stage III/IV samples (n = 1016). To further explore these altered molecular pathways, minimal spanning tree (MST) analysis was applied, leading to the formulation of metabolic biomarker hypotheses for OC liquid biopsy. To validate, a multiple reaction monitoring (MRM) based quantitative LCMS/MS method was developed. This method allowed for the precise quantification of targeted metabolite biomarkers using an OC blood cohort comprising control samples (n = 464), benign samples (n = 3), and OC samples (n = 13).

resultsEleven functional modules were identified as significant differentiators (false discovery rate, FDR < 0.05) between normal and early-stage, or early-stage and late-stage ovarian cancer (OC) tumor tissues. MST analysis revealed that the metabolic L-arginine/nitric oxide (L-ARG/NO) pathway was reprogrammed, and the modules related to "DNA replication" and "DNA repair and recombination" served as anchor modules connecting the other nine modules. Based on this analysis, symmetric dimethylarginine (SDMA) and arginine were proposed as potential liquid biopsy biomarkers for OC assessment. Our quantitative LCMS/MS analysis on our OC blood cohort provided direct evidence supporting the use of the SDMA-to-arginine ratio as a liquid biopsy panel to distinguish between normal and OC samples, with an area under the ROC curve (AUC) of 98.3%.

conclusionOur comprehensive analysis of tissue genomics and blood quantitative LC/MSMS metabolic data shed light on the metabolic reprogramming underlying OC pathophysiology. These findings offer new insights into the potential diagnostic utility of the SDMA-to-arginine ratio for OC assessment. Further validation studies using adequately powered OC cohorts are warranted to fully establish the clinical effectiveness of this diagnostic test.

Indexed as

Nitric OxideOvarian NeoplasmsArea Under CurveArginineBiopsyFemaleHumansArginineNitric OxideArginase (ARG)Asymmetric dimethylarginine (ADMA)Dimethylamine (DMA)Dimethylarginine dimethylaminohydrolase (DDAH)L-arginine/nictric oxide (L-ARG/NO)Metabolic reprogrammingNitric oxide synthase (NOS)Ovarian cancer (OC)Protein arginine methyltransferases (PRMT)Symmetric dimethylarginine (SDMA)

Identifiers

PMID37684587
PMCPMC10492322

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.