Evidence map›Paper›PMID 35749909›Full record

ArticleEuropean journal of cancer (Oxford, England : 1990)2022

Genetic variants involved in the cGAS-STING pathway predict outcome in patients with metastatic colorectal cancer: Data from FIRE-3 and TRIBE trials.

Jingyuan Wang, Yi Xiao, Fotios Loupakis, Sebastian Stintzing, Yan Yang, Hiroyuki Arai, Francesca Battaglin, Natsuko Kawanishi, Priya Jayachandran, Shivani Soni and 9 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of cancer (Oxford, England : 1990), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

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  3. Association ofLife (Basel, Switzerland) · 2025
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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

19 authors at 8 institutions in 5 countries.

Jingyuan WangDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; Center of Evidence-based Medicine, Fudan University, Shanghai, China.
Yi XiaoDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Fotios LoupakisClinical and Experimental Oncology Department, Medical Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Sebastian StintzingDepartment of Hematology, Oncology, and Cancer Immunology (CCM), Charité - Universitaetsmedizin Berlin, Germany.
Yan YangDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, 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.
Priya JayachandranDivision 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.
Christoph MancaoOncology Biomarker Development, Genentech Inc., Basel, Switzerland.
Chiara CremoliniDepartment of Translational Medicine, University of Pisa, Italy.
Tianshu LiuDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
Volker HeinemannDepartment of Medicine III, University Hospital, LMU Munich, Munich, Germany.
Alfredo FalconeDepartment of Translational Medicine, University of Pisa, Italy.
Lin ShenKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China.
Joshua MillsteinDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
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 · USUniversity of Pisa · ITCharité - Universitätsmedizin Berlin · DEFudan University · CNIstituto Oncologico Veneto · ITLMU Klinikum · DEMinistry of Education · ETSun Yat-sen University · CN

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

backgroundThe activation of stimulator of interferon genes (STING) was reported to enhance cetuximab-mediated natural killer cell activation and dendritic cell maturation. Polymorphisms in genes in the cyclic GMP-AMP synthase (cGAS)-STING pathway may affect innate immune response. Therefore, we hypothesised that genetic variants in the cGAS-STING pathway may predict the efficacy of cetuximab-based treatment in patients with metastatic colorectal cancer.

methodsGenomic DNA from blood samples of patients enrolled in FIRE-3 (cetuximab arm, n = 129; bevacizumab arm, n = 107) and TRIBE (bevacizumab arm, n = 215) was genotyped using the OncoArray-500K bead chip panel. Seven selected single nucleotide polymorphisms in 3 genes (cGAS, STING and interferon B1 (IFNB1)) were analysed for the association with overall survival and progression-free survival.

resultsIn the cetuximab cohort, patients with STING rs1131769 any T allele showed significantly shorter overall survival (36.3 versus 56.1 months) than carriers of C/C in both univariate [hazard ratio (HR) = 2.08; 95% confidence interval (CI): 1.06-4.07; P = 0.03] and multivariate (HR = 2.98; 95% CI: 1.35-6.6; P = 0.0085) analyses; patients carrying IFNB1 rs1051922 G/A and A/A genotype showed a significantly shorter progression-free survival than carriers of G/G allele in both univariate (G/A versus G/G, 10.2 versus 14.1 months, HR = 1.84; 95% CI 1.23-2.76; A/A versus G/G, 10.7 versus 14.1 months, HR = 2.19; 95% CI 0.97-4.96; P = 0.0077) and multivariate analyses (G/A versus G/G, HR = 2; 95% CI 1.22-3.3; A/A versus G/G, HR = 2.19, 95% CI 0.92-5.26, P = 0.02). These associations were not observed in the bevacizumab arm of FIRE-3 or TRIBE.

conclusionThese results suggest for the first time that germline polymorphisms in STING and IFNB1 genes may predict the outcomes of cetuximab-based treatment in patients with metastatic colorectal cancer.

Indexed as

Colonic NeoplasmsColorectal NeoplasmsRectal NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCamptothecinCetuximabFluorouracilHumansInterferonsLeucovorinMembrane ProteinsNucleotidyltransferasesSTING ProteinBevacizumabCamptothecinCetuximabFluorouracilInterferonsLeucovorinMembrane ProteinsNucleotidyltransferasesSTING1 protein, humanSTING ProteinBiomarkerCetuximabColorectal cancerSTING

Identifiers

PMID35749909
PMCPMC11970509
OpenAlexW4283207819

What OpenQuestion holds

Textmetadata
LicenceTDM
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.