Evidence map›Paper›PMID 34707195›Full record

ArticleNPJ precision oncology2021

Molecular differences between lymph nodes and distant metastases compared with primaries in colorectal cancer patients.

Alberto Puccini, Andreas Seeber, Joanne Xiu, Richard M Goldberg, Davide Soldato, Axel Grothey, Anthony F Shields, Mohamed E Salem, Francesca Battaglin, Martin D Berger and 11 more

Abstract read
In one paragraph

Article in NPJ precision oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 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

21 authors.

Alberto PucciniNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-2492-4043
Andreas SeeberDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria.
Joanne XiuCaris Life Sciences, Phoenix, AZ, USA.
Richard M GoldbergWest Virginia University Cancer Institute, Morgantown, WV, USA.
Davide SoldatoUniversity of Genoa, Medical Oncology Unit 1, Ospedale Policlinico San Martino, Genoa, Italy.ORCID http://orcid.org/0000-0002-2090-3245
Axel GrotheyWest Cancer Center, University of Tennessee, Germantown, TN, USA.ORCID http://orcid.org/0000-0002-9341-6499
Anthony F ShieldsDepartment of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Mohamed E SalemLevine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA.
Francesca BattaglinNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Martin D BergerNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Wafik S El-DeiryBrown University and Lifespan Cancer Institute (LCI), Providence, RI, USA.
Ryuma TokunagaNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Madiha NaseemNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Wu ZhangNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Sukeshi Patel AroraMays Cancer Center, UT Health San Antonio San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-1176-0713
Moh'd M KhushmanThe University of South Alabama, Mitchell Cancer Institute, Mobile, AL, USA.
Michael J HallMedical Oncology and Population Sciences, Fox Chase Cancer Center, Phoenix, AZ, USA.
Philip A PhilipDepartment of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
John L MarshallRuesch Center for The Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
W Michael KornCaris Life Sciences, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0002-0124-6841
Heinz-Josef LenzNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. lenz@med.usc.edu.ORCID http://orcid.org/0000-0003-2178-9568

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

Lymph nodes (LNs) and distant metastases can arise from independent subclones of the primary tumor. Herein, we characterized the molecular landscape and the differences between LNs, distant metastases and primary colorectal cancers (CRCs). Samples were analyzed using next generation sequencing (NGS, MiSeq on 47 genes, NextSeq on 592 genes) and immunohistochemistry. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. In total, 11,871 samples were examined, comprising primaries (N = 5862), distant (N = 5605) and LNs metastases (N = 404). The most frequently mutated genes in LNs were TP53 (72%), APC (61%), KRAS (39%), ARID1A (20%), PIK3CA (12%). LNs showed a higher mean TMB (13 mut/MB) vs distant metastases (9 mut/MB, p < 0.0001). TMB-high (≥17mut/MB) and MSI-H (8.8% and 6.9% vs 3.7%, p < 0.001 and p = 0.017, respectively) classifications were more frequent in primaries and LNs vs distant metastases (9.5% and 8.8% vs 4.2%, p < 0.001 and p = 0.001, respectively). TMB-high is significantly more common in LNs vs distant metastases and primaries (P < 0.0001), regardless MSI-H status. Overall, LNs showed significantly different rates of mutations in APC, KRAS, PI3KCA, KDM6A, and BRIP1 (p < 0.01) vs primaries, while presenting a distinct molecular profile compared to distant metastases. Our cohort of 30 paired samples confirmed the molecular heterogeneity between primaries, LNs, and distant metastases. Our data support the hypothesis that lymphatic and distant metastases harbor different mutational landscape. Our findings are hypothesis generating and need to be examined in prospective studies.

Identifiers

PMID34707195
PMCPMC8551277

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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.