ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
SMAD4 Loss in Colorectal Cancer Patients Correlates with Recurrence, Loss of Immune Infiltrate, and Chemoresistance.
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Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.
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70citing papers in PubMed, 2 pooled it
8.3field-weighted citation impact, top 2% of its field
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Who cites it
70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Prognostic role and clinicopathological features of SMAD4 gene mutation in colorectal cancer: a systematic review and meta-analysis.BMC gastroenterology · 2021Pooled it
- Association of SMAD4 loss with drug resistance in clinical cancer patients: A systematic meta-analysis.PloS one · 2021Pooled it
- NSABP FC-11: A phase II study of neratinib plus trastuzumab or neratinib plus cetuximab in patients with "quadruple wild-type" (KRAS/NRAS/BRAF/PIK3CA) metastatic colorectal cancer based on HER2 status: amplified, non-amplified (wild-type), or mutated.Cancer chemotherapy and pharmacology · 2025Trial
- Review
- Combined RAS and SMAD4 Mutations and Microsatellite Instability Predict Outcomes in Colorectal Lung Metastases Treated with Image-Guided Thermal Ablation.Annals of surgical oncology · 2026Article
- Dynamics and master transcription factors dependence of intestinal super-enhancers during differentiation and oncogenesis.Nucleic acids research · 2026Article
- Clinical impact of the methylation status of SMAD4 and AKR1B1 genes in a liquid biopsy sample as a prognostic marker for breast cancer.Scientific reports · 2026Article
- Exploratory biomarker findings from regorafenib plus toripalimab in patients with refractory metastatic colorectal cancer (REGOTORI study).Gastroenterology report · 2026Article
- Distinct Molecular and Prognostic Profiles of Left- and Right-Sided Colorectal Cancer Revealed by NGS Analysis: The Role of SMAD4 and SETD2 Mutations.Cancer medicine · 2026Article
- Unraveling Signaling Pathways in Immune Microenvironment Crosstalk to Overcome Immunotherapy Resistance in Colorectal Cancer.Human mutation · 2026Review
- Genetic, Epidemiological, Clinical, and Therapeutic Trajectories in Colon and Rectal Cancers.Cancers · 2025Review
- Biotechnological Insights into KAT2A-Mediated Epigenetic Regulation in Colorectal Cancer: A Transcriptomic and Functional Genomics Approach.Iranian journal of biotechnology · 2025Article
- GNG2 inhibits brain metastases from colorectal cancer via PI3K/AKT/mTOR signaling pathway.Scientific reports · 2025Article
- Prognostic and Immunologic Significance of SH2B2 in Colon Adenocarcinoma and its Relationship to Proliferation, Migration, and Invasion.Combinatorial chemistry & high throughput screening · 2025Article
- Exploring the molecular mechanisms and therapeutic potential of SMAD4 in colorectal cancer.Cancer biology & therapy · 2024Review
- Association between the expression of epithelial-mesenchymal transition (EMT)-related markers and oncologic outcomes of colorectal cancer.Updates in surgery · 2024Article
- Article
- CCL9/CCR1 axis-driven chemotactic nanovesicles for attenuating metastasis of SMAD4-deficient colorectal cancer by trapping TGF-Acta pharmaceutica Sinica. B · 2024Article
- A panorama of colon cancer in the era of liquid biopsy.The journal of liquid biopsy · 2024Review
- SMAD4 enhances the cytotoxic efficacy of human NK cells against colorectal cancer cells via the mFrontiers in immunology · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
35 authors at 9 institutions in 3 countries.
Isaac Wasserman *Icahn School of Medicine at Mount Sinai, New York, New York.ORCID 0000-0002-6955-0567
Lik Hang Lee *Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Shuji OginoDepartment of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Michael R MarcoColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-6731-0810
Chao WuColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Xi ChenDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida.
Jashodeep DattaDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-5052-7586
Eran SadotDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Bryan SzeglinColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-7866-7548
Jose G GuillemColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Philip B PatyColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Martin R WeiserColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Garrett M NashColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Leonard SaltzDepartment of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-8353-4670
Afsar BarlasMolecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.
Katia Manova-TodorovaMolecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.
Srijaya Prakash Babu UppadaDepartment of Biochemistry and Molecular Biology, Buffet Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska.
Arthur E ElghouayelColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Peter NtiamoahDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Jonathan N GlickmanDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Tsuyoshi HamadaDepartment of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Keisuke KosumiDepartment of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Kentaro InamuraDivision of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.ORCID 0000-0001-6444-3861
Andrew T ChanBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Reiko NishiharaDepartment of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Andrea CercekDepartment of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Karuna GaneshDepartment of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Nancy E KemenyDepartment of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Punita DhawanDepartment of Biochemistry and Molecular Biology, Buffet Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska.
Rona YaegerDepartment of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Charles L SawyersHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Julio Garcia-AguilarColorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Marios GiannakisBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Jinru ShiaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
J Joshua Smith *Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York. smithj5@mskcc.org.
Memorial Sloan Kettering Cancer Center · USBroad Institute · USDana-Farber Cancer Institute · USUniversity of Nebraska Medical Center · USAlbert Einstein College of Medicine · USBeth Israel Deaconess Medical Center · USBrigham and Women's Hospital · USJapanese Foundation For Cancer Research · JPUniversity of Miami · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8MStatistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI TWOROGER, SHELLEY S · 2000 to 2019
$77.8MUNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Apar Kishor Ganti · 1985 to 2026
$55.0MValidity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI SPIEGELMAN, DONNA L · 1991 to 2009
$41.8MLong Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3MCancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0MCancer Epidemiology Cohort in Male Health ProfessionalsUM1CA167552 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2012 to 2016
$11.5MInflammation and Colorectal NeoplasiaR01CA137178 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHAN, ANDREW T · 2009 to 2019
$6.5MSummer research experiences for medical students supervised by faculty mentorsR25CA020449 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Charlotte Eielson Ariyan · 1985 to 2026
$6.2MAccelerating Transdisciplinary Epidemiology of Colorectal CancerR35CA197735 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2015 to 2021
$6.0MOrgan Preservation in Rectal AdenocarcinomaR01CA182551 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI GARCIA-AGUILAR, JULIO · 2014 to 2018
$3.1MBLRD VA I01 BX002086Howard Hughes Medical InstituteNCI NIH HHS K07 CA122826NCI NIH HHS K07 CA190673NCI NIH HHS K08 CA230213NCI NIH HHS L30 CA209253NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA036727NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA124977NCI NIH HHS R01 CA137178NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA158472NCI NIH HHS R01 CA182551NCI NIH HHS R21 CA119005NCI NIH HHS R21 CA216746NCI NIH HHS R25 CA020449NCI NIH HHS R35 CA197735NCI NIH HHS U01 CA167552NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA186107NIDDK NIH HHS K24 DK098311
Abstract
purposeSMAD4 has shown promise in identifying patients with colorectal cancer at high risk of recurrence or death.
resultsThe discovery cohort consisted of 364 patients with stage I-IV colorectal cancer. Median age at diagnosis was 53 years. The cohort consisted of 61% left-sided tumors and 62% stage II/III patients. Median follow-up was 5.4 years (interquartile range, 2.3-8.2). SMAD4 loss, noted in 13% of tumors, was associated with higher tumor and nodal stage, adjuvant therapy use, fewer tumor-infiltrating lymphocytes (TIL), and lower peritumoral lymphocyte aggregate (PLA) scores (all
conclusionsOur data show SMAD4 loss correlates with worse clinical outcome, resistance to chemotherapy, and decreased immune infiltrate, supporting its use as a prognostic marker in patients with colorectal cancer.
Indexed as
AdultAgedAnimalsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChemotherapy, AdjuvantColonColorectal NeoplasmsDisease-Free SurvivalDrug Resistance, NeoplasmFemaleFluorouracilFollow-Up StudiesHumansLymphocytes, Tumor-InfiltratingMaleBiomarkers, TumorFluorouracilSmad4 ProteinSMAD4 protein, human
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