Trial reportPloS one2015
Immune response gene expression in colorectal cancer carries distinct prognostic implications according to tissue, stage and site: a prospective retrospective translational study in the context of a hellenic cooperative oncology group randomised trial.
Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
16 citing papers in PubMed, 3 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Defining the Prognostic Significance of BRAF V600E in Early-Stage Colon Cancer: A Systematic Review and Meta-Analysis.Current oncology (Toronto, Ont.) · 2025Pooled it
- Pooled it
- Pooled it
- Evaluation of the prognostic value of CD3, CD8, and FOXP3 mRNA expression in early-stage breast cancer patients treated with anthracycline-based adjuvant chemotherapy.Cancer medicine · 2018Trial
- Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group.Journal of translational medicine · 2017Trial
- Evaluation of CpG Island Methylator Phenotype as a Biomarker in Colorectal Cancer Treated With Adjuvant Oxaliplatin.Clinical colorectal cancer · 2016Trial
- Tumour immune microenvironment biomarkers predicting cytotoxic chemotherapy efficacy in colorectal cancer.Journal of clinical pathology · 2021Review
- Article
- Analysis of prognosis, genome, microbiome, and microbial metabolome in different sites of colorectal cancer.Journal of translational medicine · 2019Article
- Prognostic significance of tumor genotypes and CD8+ infiltrates in stage I-III colorectal cancer.Oncotarget · 2018Article
- Immunohistochemical distribution of FOXP3+ regulatory T cells in colorectal cancer patients.International journal of clinical and experimental pathology · 2018Article
- Evaluation of the Prognostic Value of RANK, OPG, and RANKL mRNA Expression in Early Breast Cancer Patients Treated with Anthracycline-Based Adjuvant Chemotherapy.Translational oncology · 2017Article
- The significance of tumor-associated immune response in molecular taxonomy, prognosis and therapy of colorectal cancer patients.Annals of translational medicine · 2016Review
- Towards tumor immunodiagnostics.Annals of translational medicine · 2016Review
- Assessment of clinically related outcomes and biomarker analysis for translational integration in colorectal cancer (ACROBATICC): study protocol for a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastasis.Journal of translational medicine · 2016Article
- Article
Corrections and comments
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Authors and funding
20 authors at 11 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough host immune response is an emerging prognostic factor for colorectal cancer, there is no consensus on the optimal methodology, surrogate markers or tissue for study. PATIENTS AND
methodsTumour blocks were prospectively collected from 344 patients with stage II/III colorectal cancer (CRC) treated with adjuvant chemotherapy. Whole section lymphocytic infiltration was studied along with mRNA expression of CD3Z, CD8, CD4, CXCL9, CXCL13, IGHM, FOXP3, SNAI2 and ESR1 by qRT-qPCR in tissue microarray (TMA) cores from the centre of tumour, invasive margin and adjacent normal mucosa.
resultsLymphocytic infiltration, deficient MMR (10.9%), KRAS (40.7%) and BRAF (4.9%) mutations or single mRNA gene expression were not prognostic. Tumour ESR1 gene expression (Hazard Ratio [HR] for relapse 2.33, 95% CI 1.35-4.02; HR for death 1.74, 95% CI 1.02-2.97) and absence of necrosis (HR for relapse 1.71, 95% CI 1.05-2.71; HR for death 1.98, 95% CI 1.14-3.43) were adverse prognostic features. We used CD3Z and CD8 expression in order to devise the mRNA-based Immune Score (mIS) and proceeded to partitioning analysis in 267 patients, with age, stage, tumour site (Right vs Left CRC), KRAS mutation and tumour mIS as input factors. Only in patients with stage III right-sided colon cancer, a low immune response was associated with inferior disease-free survival (mIS-low, HR for relapse 2.28, 95% CI 1.05-8.02). No prognostic significance was seen for tumour mIS in any other stage or site of CRC, or for a similar mIS score derived from adjacent normal mucosa. Independent adverse prognostic significance was retained in multivariable analysis for absence of necrosis, tumour ESR1 expression in all patients and low tumour mIS in stage III right-sided CRC.
conclusionsIn localised CRC, mRNA-based CD3Z/CD8 profiling of tumour immune response may have stage, site and tissue-specific prognostic significance, along with ESR1 expression.
trial registrationANZCTR.org.au ACTRN12610000509066.
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