Evidence map›Paper›PMID 36681091›Full record

ArticleThe Lancet. Oncology2023

Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study.

Jingyuan Wang, Joanne Xiu, Alex Farrell, Yasmine Baca, Hiroyuki Arai, Francesca Battaglin, Natsuko Kawanishi, Shivani Soni, Wu Zhang, Joshua Millstein and 14 more

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

Article in The Lancet. Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
20.7field-weighted citation impact, top 1% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 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

24 authors at 12 institutions in 2 countries.

Jingyuan WangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Medical Oncology, Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Joanne XiuCaris Life Sciences, Phoenix, AZ, USA.
Alex FarrellCaris Life Sciences, Phoenix, AZ, USA.
Yasmine BacaCaris Life Sciences, Phoenix, AZ, USA.
Hiroyuki AraiDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Francesca BattaglinDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Natsuko KawanishiDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Shivani SoniDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Wu ZhangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Joshua MillsteinDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Anthony F ShieldsDepartment of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Axel GrotheyWest Cancer Center and Research Institute, Germantown, TN, USA.
Benjamin A WeinbergRuesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
John L MarshallRuesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Emil LouDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Moh'd KhushmanDepartments of Interdisciplinary Clinical Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA.
Davendra P S SohalDivision of Hematology/Oncology, University of Cincinnati, Cincinnati, OH, USA.
Michael J HallDepartment of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
Tianshu LiuDepartment of Medical Oncology, Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Matthew OberleyCaris Life Sciences, Phoenix, AZ, USA.
David SpetzlerCaris Life Sciences, Phoenix, AZ, USA.
W Michael KornCaris Life Sciences, Phoenix, AZ, USA.
Lin ShenKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Heinz-Josef LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: lenz@usc.edu.
University of Southern California · USCaris Life Sciences (United States) · USGeorgetown University · USFox Chase Cancer Center · USFudan University · CNPeking University Cancer Hospital · CNThe Barbara Ann Karmanos Cancer Institute · USUniversity of Cincinnati · USUniversity of Minnesota · USUniversity of South Alabama · USWest Cancer Center · USZhongshan Hospital · CN

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
NCI NIH HHS P30 CA006927NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

backgroundGenomic signatures contributing to high tumour mutational burden (TMB-H) independent from mismatch-repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status are not well studied. We aimed to characterise molecular features of microsatellite stable (MSS) TMB-H gastrointestinal tumours.

methodsMolecular alterations of 48 606 gastrointestinal tumours from Caris Life Sciences (CARIS) identified with next-generation sequencing were compared among MSS-TMB-H, dMMR/MSI-H, and MSS-TMB-low (L) tumours, using χ

findingsMSS-TMB-H was observed in 1600 (3·29%) of 48 606 tumours, dMMR/MSI-H in 2272 (4·67%), and MSS-TMB-L in 44 734 (92·03%). Gene mutations in SMAD2, MTOR, NFE2L2, RB1, KEAP1, TERT, and RASA1 might impair antitumour immune response despite TMB-H, while mutations in 16 other genes (CDC73, CTNNA1, ERBB4, EZH2, JAK2, MAP2K1, MAP2K4, PIK3R1, POLE, PPP2R1A, PPP2R2A, PTPN11, RAF1, RUNX1, STAG2, and XPO1) were related to TMB-H with enhanced antitumour immune response independent of dMMR/MSI-H, constructing a predictive model (modified TMB [mTMB]) for immune checkpoint inhibitor efficacy. Patients with any mutation in the mTMB gene signature, in comparison with patients with mTMB wildtype tumours, showed a superior survival benefit from immune checkpoint inhibitors in MSS gastrointestinal cancers in the CARIS cohort (n=95, median overall survival 18·77 months [95% CI 17·30-20·23] vs 7·03 months [5·73-8·34]; hazard ratio 0·55 [95% CI 0·31-0·99], p=0·044). In addition, copy number amplification in chromosome 11q13 (eg, CCND1, FGF genes) was more prevalent in MSS-TMB-H tumours than in the dMMR/MSI-H or MSS-TMB-L subgroups.

interpretationNot all mutations related to TMB-H can enhance antitumour immune response. More composite biomarkers should be investigated (eg, mTMB signature) to tailor treatment with immune checkpoint inhibitors. Our data also provide novel insights for the combination of immune checkpoint inhibitors and drugs targeting cyclin D1 or FGFs.

fundingUS National Cancer Institute, Gloria Borges WunderGlo Foundation, Dhont Family Foundation, Gene Gregg Pancreas Research Fund, San Pedro Peninsula Cancer Guild, Daniel Butler Research Fund, Victoria and Philip Wilson Research Fund, Fong Research Project, Ming Hsieh Research Fund, Shanghai Sailing Program, China National Postdoctoral Program for Innovative Talents, China Postdoctoral Science Foundation, National Natural Science Foundation of China.

Indexed as

Colorectal NeoplasmsGastrointestinal NeoplasmsBrain NeoplasmsChinaHumansImmune Checkpoint InhibitorsKelch-Like ECH-Associated Protein 1Microsatellite InstabilityMicrosatellite RepeatsMutationNeoplastic Syndromes, HereditaryNF-E2-Related Factor 2p120 GTPase Activating ProteinRetrospective StudiesImmune Checkpoint InhibitorsKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2p120 GTPase Activating ProteinRASA1 protein, human

Identifiers

PMID36681091
PMCPMC10599647
OpenAlexW4317356384

What OpenQuestion holds

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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 OpenQuestion graph.