Evidence map›Paper›PMID 37071673›Full record

ArticleCancer discovery2023

Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma.

Michal Marek Hoppe, Patrick Jaynes, Fan Shuangyi, Yanfen Peng, Shruti Sridhar, Phuong Mai Hoang, Clementine Xin Liu, Sanjay De Mel, Limei Poon, Esther Hian Li Chan and 32 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

7 citing papers in PubMed, 7 citations in OpenAlex.

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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

42 authors at 13 institutions in 7 countries.

Michal Marek HoppeCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-0364-6080
Patrick JaynesCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-3297-8674
Fan ShuangyiDepartment of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID 0000-0001-6303-6527
Yanfen PengCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0003-1753-8547
Shruti SridharCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-0388-0352
Phuong Mai HoangCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-9629-5653
Clementine Xin LiuDepartment of Haematology-Oncology, National University Health System, Singapore, Singapore.ORCID 0000-0003-4172-5238
Sanjay De MelDepartment of Haematology-Oncology, National University Health System, Singapore, Singapore.ORCID 0000-0002-8881-3537
Limei PoonDepartment of Haematology-Oncology, National University Health System, Singapore, Singapore.ORCID 0000-0002-8854-9414
Esther Hian Li ChanDepartment of Haematology-Oncology, National University Health System, Singapore, Singapore.ORCID 0000-0003-1006-5601
Joanne LeeDepartment of Haematology-Oncology, National University Health System, Singapore, Singapore.ORCID 0000-0001-9012-598X
Choon Kiat OngDivision of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore, Singapore.ORCID 0000-0001-6402-4288
Tiffany TangDivision of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.ORCID 0000-0002-6701-703X
Soon Thye LimDivision of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.ORCID 0000-0002-0366-5505
Chandramouli NagarajanDepartment of Haematology, Singapore General Hospital, Singapore, Singapore.ORCID 0000-0001-5755-2226
Nicholas F GrigoropoulosDepartment of Haematology, Singapore General Hospital, Singapore, Singapore.ORCID 0000-0002-8033-5024
Soo-Yong TanDepartment of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-6348-2823
Susan Swee-Shan HueDepartment of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID 0000-0003-1854-1481
Sheng-Tsung ChangDepartment of Pathology, Chi-Mei Medical Center, Tainan City, Taiwan.ORCID 0000-0003-4544-6623
Shih-Sung ChuangDepartment of Pathology, Chi-Mei Medical Center, Tainan City, Taiwan.ORCID 0000-0003-3971-525X
Shaoying LiDepartment of Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-6857-0523
Joseph D KhouryDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.ORCID 0000-0003-2621-3584
Hyungwon ChoiDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-6687-3088
Carl HarrisF. Hoffmann-La Roche Ltd, Basel, Switzerland.ORCID 0000-0002-9807-1274
Alessia BottosF. Hoffmann-La Roche Ltd, Basel, Switzerland.ORCID 0000-0001-6311-2833
Laura J GayWellcome MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom.ORCID 0000-0002-9758-8677
Hendrik F P RungeWellcome MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom.
Ilias MoutsopoulosWellcome MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom.ORCID 0000-0003-4584-7849
Irina MohorianuWellcome MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom.ORCID 0000-0003-4863-761X
Daniel J HodsonWellcome MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom.ORCID 0000-0001-6225-2033
Pedro FarinhaBC Cancer Research Centre, Vancouver, Canada.ORCID 0000-0001-9364-9391
Anja MottokBC Cancer Research Centre, Vancouver, Canada.ORCID 0000-0003-3125-0494
David W ScottBC Cancer Research Centre, Vancouver, Canada.ORCID 0000-0002-0435-5947
Jason J PittCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-7534-4516
Jinmiao ChenSingapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.ORCID 0000-0001-7547-6423
Gayatri KumarTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-3686-5471
Kasthuri KannanTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-6993-5141
Wee Joo ChngCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0003-2578-8335
Yen Lin CheeDepartment of Haematology-Oncology, National University Health System, Singapore, Singapore.ORCID 0000-0002-8176-8382
Siok-Bian NgCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0001-6051-6410
Claudio TripodoTumor Immunology Unit, University of Palermo, Palermo, Italy.ORCID 0000-0002-0821-6231
Anand D JeyasekharanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0001-9816-6137
National University of Singapore · SGWellcome/MRC Cambridge Stem Cell Institute · GBNational Cancer Centre Singapore · SGOccupational Cancer Research Centre · CAThe University of Texas MD Anderson Cancer Center · USChi Mei Medical Center · TWRoche (Switzerland) · CHSingapore General Hospital · SGAgency for Science, Technology and Research · SGIFOM · ITNational University Health System · SGSingapore Immunology Network · SGUniversity of Nebraska Medical Center · US

Funding

Medical Research Council MC_PC_17230Wellcome Trust
6 · The paper itself

Abstract

Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6- (M+2+6-) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6- percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and MYC/BCL2/BCL6-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6- unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance. SIGNIFICANCE: Using single-cell-resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer. This article is highlighted in the In This Issue feature, p. 1027.

Indexed as

Lymphoma, Large B-Cell, DiffusePhosphatidylinositol 3-KinasesHumansOncogenesPrognosisProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-myc

Identifiers

PMID37071673
PMCPMC10157367
OpenAlexW4366238718

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.