Evidence map›Paper›PMID 38986529›Full record

ArticleThe oncologist2024

Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors.

Dan Morgenstern-Kaplan, Samuel A Kareff, Asaad Trabolsi, Estelamari Rodriguez, Harris Krause, Jennifer R Ribeiro, Heng Tan, Emmanuel S Antonarakis, Emil Lou, Misako Nagasaka and 10 more

Abstract read
In one paragraph

Article in The oncologist, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed.

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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

20 authors.

Dan Morgenstern-KaplanDepartment of Medicine, Division of Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33131, United States.ORCID 0000-0002-9031-2256
Samuel A KareffDepartment of Medicine, Division of Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33131, United States.ORCID 0000-0001-7431-1221
Asaad TrabolsiDepartment of Medicine, Division of Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33131, United States.ORCID 0000-0002-2479-1797
Estelamari RodriguezDepartment of Medicine, Division of Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33131, United States.ORCID 0000-0001-8132-4573
Harris KrauseCaris Life Sciences, Phoenix, AZ 85040, United States.ORCID 0000-0003-3481-8364
Jennifer R RibeiroCaris Life Sciences, Phoenix, AZ 85040, United States.ORCID 0000-0002-1685-8568
Heng TanDepartment of Medicine, Division of Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33131, United States.
Emmanuel S AntonarakisUniversity of Minnesota Masonic Cancer Center, Minneapolis, MN 55455, United States.ORCID 0000-0003-3531-3851
Emil LouUniversity of Minnesota Masonic Cancer Center, Minneapolis, MN 55455, United States.ORCID 0000-0002-1607-1386
Misako NagasakaDivision of Hematology/Oncology, University of California Irvine School of Medicine, Orange, CA 92617, United States.ORCID 0000-0001-5308-615X
Sandra AlgazeDivision of Medical Oncology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, United States.ORCID 0000-0001-7233-5019
Heinz-Josef LenzDivision of Medical Oncology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, United States.ORCID 0000-0003-2178-9568
Stephen V LiuGeorgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, United States.
Balazs HalmosMontefiore Einstein Comprehensive Cancer Center, Bronx, NY 10461, United States.ORCID 0000-0001-7548-8360
Dave S B HoonSaint John's Cancer Institute, Providence Health System, Santa Monica, CA 90404, United States.ORCID 0000-0003-1915-3683
Andreas SeeberTyrolean Cancer Research Institute, Innsbruck Medical University, Innsbruck 6020, Austria.ORCID 0000-0003-4401-8248
Patrick C MaDivision of Hematology/Oncology, Penn State Cancer Institute, Hershey, PA 17033, United States.
Wafik S El-DeiryLegorreta Cancer Center, Warren Alpert Medical School of Brown University, Providence, RI 02912, United States.ORCID 0000-0002-9577-8266
Ari M VanderwaldeCaris Life Sciences, Phoenix, AZ 85040, United States.ORCID 0000-0002-6842-2563
Gilberto LopesDepartment of Medicine, Division of Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33131, United States.ORCID 0000-0002-1151-9903

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller · 1998 to 2026
$100.4M
NCI NIH HHS P30 CA077598
6 · The paper itself

Abstract

backgroundTROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach.

methodsBreast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts.

resultsSeveral pathogenic mutations were associated with TACSTD2-high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2-high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2-low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS-mutant tumors. Patients with breast cancer with TACSTD2-high tumors also experienced significantly worse OS following immune checkpoint inhibitors.

conclusionsTACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors.

Indexed as

Antigens, NeoplasmCell Adhesion MoleculesAgedBiomarkers, TumorFemaleGenomicsHumansMaleMiddle AgedMutationNeoplasmsPrognosisAntigens, NeoplasmBiomarkers, TumorCell Adhesion MoleculesTACSTD2 protein, humanprecision oncologytargeted therapyTROP2tumor genetics

Identifiers

PMID38986529
PMCPMC11546728

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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 OpenQuestion graph.