Evidence map›Paper›PMID 34108518›Full record

ArticleScientific reports2021

Random survival forests identify pathways with polymorphisms predictive of survival in KRAS mutant and KRAS wild-type metastatic colorectal cancer patients.

Madiha Naseem, Shu Cao, Dongyun Yang, Joshua Millstein, Alberto Puccini, Fotios Loupakis, Sebastian Stintzing, Chiara Cremolini, Ryuma Tokunaga, Francesca Battaglin and 7 more

Open access · goldAbstract read

PubMed Full text at PMC Publisher

In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it

0cells of the map it votes in

4citing papers in PubMed

0.3field-weighted citation impact, top 42% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

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

17 authors at 5 institutions in 3 countries.

Madiha NaseemDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.

Shu CaoDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Dongyun YangDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Joshua MillsteinDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Alberto PucciniDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.

Fotios LoupakisOncologia Medica 1, Istituto Oncologico Veneto, Istituto Di Ricovero E Cura a Carattere Scientifico, Via Gattamelata, Padua, Italy.

Sebastian StintzingMedical Department, Division of Hematology, Oncology and Hematology, Tumor Immunology (CCM), Charité-Universitätsmedizin, Berlin, Germany.

Chiara CremoliniOncologia Medica, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma, Pisa, Italy.

Ryuma TokunagaDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.

Francesca BattaglinDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.

Shivani SoniDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.

Martin D BergerDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.

Afsaneh BarziDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.

Wu ZhangDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA.

Alfredo FalconeOncologia Medica, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma, Pisa, Italy.

Volker HeinemannDepartment of Medicine and Comprehensive Cancer Center, Ludwig-Maximilians-University Munich, Munich, Germany.

Heinz-Josef LenzDivision of Medical Oncology, Sharon Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90033, USA. lenz@usc.edu.

University of Southern California · USAzienda Ospedaliera Universitaria Pisana · ITIstituto Oncologico Veneto · ITCharité - Universitätsmedizin Berlin · DELudwig-Maximilians-Universität München · DE

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026

$181.4M

NCI NIH HHS P30 CA014089NIH Clinical Center P30CA014089

6 · The paper itself

Abstract

KRAS status serves as a predictive biomarker of response to treatment in metastatic colorectal cancer (mCRC). We hypothesize that complex interactions between multiple pathways contribute to prognostic differences between KRAS wild-type and KRAS mutant patients with mCRC, and aim to identify polymorphisms predictive of clinical outcomes in this subpopulation. Most pathway association studies are limited in assessing gene-gene interactions and are restricted to an individual pathway. In this study, we use a random survival forests (RSF) method for identifying predictive markers of overall survival (OS) and progression-free survival (PFS) in mCRC patients treated with FOLFIRI/bevacizumab. A total of 486 mCRC patients treated with FOLFIRI/bevacizumab from two randomized phase III trials, TRIBE and FIRE-3, were included in the current study. Two RSF approaches were used, namely variable importance and minimal depth. We discovered that Wnt/β-catenin and tumor associated macrophage pathway SNPs are strong predictors of OS and PFS in mCRC patients treated with FOLFIRI/bevacizumab independent of KRAS status, whereas a SNP in the sex-differentiation pathway gene, DMRT1, is strongly predictive of OS and PFS in KRAS mutant mCRC patients. Our results highlight RSF as a useful method for identifying predictive SNPs in multiple pathways.

Indexed as

MutationPolymorphism, Single NucleotideAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorColorectal NeoplasmsFemaleHumansLiver NeoplasmsMaleMiddle AgedPrognosisProto-Oncogene Proteins p21(ras)Survival RateBiomarkers, TumorKRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID34108518

DOI10.1038/s41598-021-91330-z

PMCPMC8190302

OpenAlexW3171197041

What Socratic 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 Socratic graph.