Evidence map›Paper›PMID 35331214›Full record

ArticleBMC medicine2022

Combined impact of lipidomic and genetic aberrations on clinical outcomes in metastatic castration-resistant prostate cancer.

Blossom Mak, Hui-Ming Lin, Edmond M Kwan, Heidi Fettke, Ben Tran, Ian D Davis, Kate Mahon, Martin R Stockler, Karen Briscoe, Gavin Marx and 17 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

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  14. Targeting lipid metabolism in metastatic prostate cancer.Therapeutic advances in medical oncology · 2023
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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

27 authors at 17 institutions in 2 countries.

Blossom MakChris O'Brien Lifehouse, Missenden Rd, Camperdown, New South Wales, 2050, Australia.
Hui-Ming LinGarvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
Edmond M KwanMonash Health, Melbourne, Victoria, Australia.
Heidi FettkePeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Ben TranPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Ian D DavisEastern Health Clinical School, Monash University, Melbourne, Victoria, Australia.
Kate MahonChris O'Brien Lifehouse, Missenden Rd, Camperdown, New South Wales, 2050, Australia.
Martin R StocklerUniversity of Sydney, Sydney, New South Wales, Australia.
Karen BriscoeMid North Coast Cancer Institute, Coffs Harbour, New South Wales, Australia.
Gavin MarxSydney Adventist Hospital, Wahroonga, New South Wales, Australia.
Alison ZhangChris O'Brien Lifehouse, Missenden Rd, Camperdown, New South Wales, 2050, Australia.
Megan CrumbakerGarvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
Winston TanMayo Clinic, Jacksonville, FL, USA.
Kevin HuynhBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Thomas G MeikleBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Natalie A MellettBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Andrew J HoySchool of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia.
Pan DuPredicine, Inc., Hayward, CA, USA.
Jianjun YuPredicine, Inc., Hayward, CA, USA.
Shidong JiaPredicine, Inc., Hayward, CA, USA.
Anthony M JoshuaGarvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
David J WaughQueensland University of Technology, Brisbane, Queensland, Australia.
Lisa M ButlerAdelaide Medical School and Freemason's Foundation Centre for Men's Health, University of Adelaide, Adelaide, South Australia, Australia.
Manish KohliHuntsman Cancer Institute, Salt Lake City, UT, USA.
Peter J MeikleBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Arun A AzadPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Lisa G HorvathChris O'Brien Lifehouse, Missenden Rd, Camperdown, New South Wales, 2050, Australia. lisa.horvath@lh.org.au.
Baker Heart and Diabetes Institute · AUChris O’Brien Lifehouse · AUThe Kinghorn Cancer Centre · AUUniversity of Melbourne · AUUniversity of Sydney · AUConcord Repatriation General Hospital · AUEastern Health · AUFreemasons Foundation Centre for Men's Health · AUGarvan Institute of Medical Research · AUHuntsman Cancer Institute · USMayo Clinic in Florida · USMonash Health · AUNorthern Cancer Institute · AUPeter MacCallum Cancer Centre · AUQueensland University of Technology · AURoyal Prince Alfred Hospital · AUSydney Adventist Hospital · AU

Funding

Cell free nucleic acid-based biomarkers in advanced prostate cancerR01CA212097 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI KOHLI, MANISH, WANG, LIANG · 2017 to 2022
$3.1M
NCI NIH HHS R01 CA212097
6 · The paper itself

Abstract

backgroundBoth changes in circulating lipids represented by a validated poor prognostic 3-lipid signature (3LS) and somatic tumour genetic aberrations are individually associated with worse clinical outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). A key question is how the lipid environment and the cancer genome are interrelated in order to exploit this therapeutically. We assessed the association between the poor prognostic 3-lipid signature (3LS), somatic genetic aberrations and clinical outcomes in mCRPC.

methodsWe performed plasma lipidomic analysis and cell-free DNA (cfDNA) sequencing on 106 men with mCRPC commencing docetaxel, cabazitaxel, abiraterone or enzalutamide (discovery cohort) and 94 men with mCRPC commencing docetaxel (validation cohort). Differences in lipid levels between men ± somatic genetic aberrations were assessed with t-tests. Associations between the 3LS and genetic aberrations with overall survival (OS) were examined using Kaplan-Meier methods and Cox proportional hazard models.

resultsThe 3LS was associated with shorter OS in the discovery (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.4-3.3, p < 0.001) and validation cohorts (HR 2.32, 95% CI 1.59-3.38, p < 0.001). Elevated plasma sphingolipids were associated with AR, TP53, RB1 and PI3K aberrations (p < 0.05). Men with both the 3LS and aberrations in AR, TP53, RB1 or PI3K had shorter OS than men with neither in both cohorts (p ≤ 0.001). The presence of 3LS and/or genetic aberration was independently associated with shorter OS for men with AR, TP53, RB1 and PI3K aberrations (p < 0.02). Furthermore, aggressive-variant prostate cancer (AVPC), defined as 2 or more aberrations in TP53, RB1 and/or PTEN, was associated with elevated sphingolipids. The combination of AVPC and 3LS predicted for a median survival of ~12 months. The relatively small sample size of the cohorts limits clinical applicability and warrants future studies.

conclusionsElevated circulating sphingolipids were associated with AR, TP53, RB1, PI3K and AVPC aberrations in mCRPC, and the combination of lipid and genetic abnormalities conferred a worse prognosis. These findings suggest that certain genotypes in mCRPC may benefit from metabolic therapies.

Indexed as

Prostatic Neoplasms, Castration-ResistantBiomarkers, TumorDocetaxelHumansLipidomicsLipidsMalePhosphatidylinositol 3-KinasesReceptors, AndrogenSphingolipidsBiomarkers, TumorDocetaxelLipidsPhosphatidylinositol 3-KinasesReceptors, AndrogenSphingolipidsAndrogen receptorBiomarkerCastration-resistant prostate cancerGenomicsLipidPI3KRB1TP53

Identifiers

PMID35331214
PMCPMC8953070
OpenAlexW3216139210

What OpenQuestion holds

Textmetadata
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.