Identification of a novel immune signature for optimizing prognosis and treatment prediction in colorectal cancer

e16054 Background: Several studies have displayed a sustained clinical response to immune checkpoint inhibitors with profound clinical improvement in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). MSI-H tumors may display higher numbers of TILs, many of which can be directed against tumor-related neoantigens. We set out to examine the underline mechanism in gene level to further explain the differences between MSI-H and MSS CRC. Methods: Whole exome sequencing(WES) was performed on 68 CRC patient.MSI status of these patients were determined using a targeted next generation sequencing panel covering 100 MSI loci. TCGA database was used to analyze WES data of 364 CRC patients with different MSI states, and immune signature was used to analyze the corresponding relationship of immune cell expression in different populations. Results: Of 56 MSS patients, 58.9% (33/56) had copy number variants (CNV) in DIDO1, and 1.8 (1/56) had single nucleotide variants(SNV) in DIDO1. Of 12 MSI-H patients, 33.3% (4/12) had SNV in DIDO1 gene, None had CNV in DIDO1. TCGA database showed that of 308 MSS patients, 8% (24/308) had CNV in DIDO1 and 3% (9/308) had SNV in DIDO1. Of 56 MSI-H patient, 39% (22/56) had SNV in DIDO1 and only one patent had both SNV and CNV in DIDO1. Gene variation of DIDO1 of 68 CRC patients showed a correlation with TCGA database. Gene variation of DIDO1 in MSI-H patients are mainly SNV, and the incidence of CNV is very small (4.3% of DIDO variation).While, gene variation of DIDO1 in MSS patients are mainly CNV, followed by SNV, indicating DIDO1 CNV are highly possible occurring in MSS patients. Furthermore we analyzed the relationship between the copy number of DIDO1 and immune signature through CRC TCGA database. The results showed increase of DIDO1 copy number was negatively correlated with the abundance of NK cells (P = 0.00048), T cells (P = 8.23×10-5) and macrophages (P = 1.75×10-8). Conclusions: Our results showed that different MSI status display unique patent of DIDO1 gene variation, which may be related to different immune micro environment among MSI-H/MSS patients.

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Interferon‑induced protein 16 expression in colorectal cancer and its correlation with proliferation and immune signature markers

Oncology Letters ◽

10.3892/ol.2021.12948 ◽

2021 ◽

Vol 22 (3) ◽

Author(s):

Yunlian Zou ◽

Jinping Zhang ◽

Lichen Zhang ◽

Xinmin Yan

Keyword(s):

Colorectal Cancer ◽

Immune Signature

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Hist-Immune signature: a prognostic factor in colorectal cancer using immunohistochemical slide image analysis

OncoImmunology ◽

10.1080/2162402x.2020.1841935 ◽

2020 ◽

Vol 9 (1) ◽

pp. 1841935

Author(s):

Ke Zhao ◽

Zhenhui Li ◽

Yong Li ◽

Su Yao ◽

Yanqi Huang ◽

...

Keyword(s):

Colorectal Cancer ◽

Image Analysis ◽

Prognostic Factor ◽

Immune Signature ◽

Slide Image

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Intratumoural immune signature to identify patients with primary colorectal cancer who do not require follow-up after resection: an observational study

Health Technology Assessment ◽

10.3310/hta25020 ◽

2021 ◽

Vol 25 (2) ◽

pp. 1-32

Author(s):

John N Primrose ◽

Siân A Pugh ◽

Gareth Thomas ◽

Matthew Ellis ◽

Karwan Moutasim ◽

...

Keyword(s):

Colorectal Cancer ◽

Observational Study ◽

Health Technology Assessment ◽

Technology Assessment ◽

Tissue Microarrays ◽

Health Technology ◽

Cell Counting ◽

Primary Colorectal Cancer ◽

Immune Signature

Background Following surgical and adjuvant treatment of primary colorectal cancer, many patients are routinely followed up with axial imaging (most commonly computerised tomography imaging) and blood carcinoembryonic antigen (a tumour marker) testing. Because fewer than one-fifth of patients will relapse, a large number of patients are followed up unnecessarily. Objectives To determine whether or not the intratumoural immune signature could identify a cohort of patients with a relapse rate so low that follow-up is unnecessary. Design An observational study based on a secondary tissue collection of the tumours from participants in the FACS (Follow-up After Colorectal Cancer Surgery) trial. Setting and participants Formalin-fixed paraffin-embedded tumour tissue was obtained from 550 out of 1202 participants in the FACS trial. Tissue microarrays were constructed and stained for cluster of differentiation (CD)3+ and CD45RO+ T lymphocytes as well as standard haematoxylin and eosin staining, with a view to manual and, subsequently, automated cell counting. Results The tissue microarrays were satisfactorily stained for the two immune markers. Manual cell counting proved possible on the arrays, but manually counting the number of cores for the entire study was found to not be feasible; therefore, an attempt was made to use automatic cell counting. Although it is clear that this approach is workable, there were both hardware and software problems; therefore, reliable data could not be obtained within the time frame of the study. Limitations The main limitations were the inability to use machine counting because of problems with both hardware and software, and the loss of critical scientific staff. Findings from this research indicate that this approach will be able to count intratumoural immune cells in the long term, but whether or not the original aim of the project proved possible is not known. Conclusions The project was not successful in its aim because of the failure to achieve a reliable counting system. Future work Further work is needed to perfect immune cell machine counting and then complete the objectives of this study that are still relevant. Trial registration Current Controlled Trials ISRCTN41458548. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 2. See the NIHR Journals Library website for further project information.

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Clinical Significance and Inflammatory Landscape of aNovel Recurrence-Associated Immune Signature in Stage II/III Colorectal Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.702594 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zaoqu Liu ◽

Taoyuan Lu ◽

Jing Li ◽

Libo Wang ◽

Kaihao Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Group ◽

Early Stage ◽

Recurrence Risk ◽

High Risk Group ◽

Stage Ii ◽

Immune Checkpoints ◽

Immune Signature ◽

Molecular Features ◽

Number Of Patients

BackgroundA considerable number of patients with stage II/III colorectal cancer (CRC) will relapse within 5 years after surgery, which is a leading cause of death in early-stage CRC. The current TNM stage system is limited due to the heterogeneous clinical outcomes displayed in patients of same stage. Therefore, searching for a novel tool to identify patients at high recurrence-risk for improving post-operative individual management is an urgent need.MethodsUsing four independent public cohorts and qRT-PCR data from 66 tissues, we developed and validated a recurrence-associated immune signature (RAIS) based on global immune genes. The clinical and molecular features, tumor immune microenvironment landscape, and immune checkpoints profiles of RAIS were also investigated.ResultsIn five independent cohorts, this novel scoring system was proven to be an independent recurrent factor and displayed excellent discrimination and calibration in predicting the recurrence-risk at 1~5 years. Further analysis revealed that the high-risk group displayed high mutation rate of TP53, while the low-risk group had more abundance of activated CD4+/CD8+ T cells and high expression of PD-1/PD-L1.ConclusionsThe RAIS model is highly predictive of recurrence in patients with stage II/III CRC, which might serve as a powerful tool to further optimize decision-making in adjuvant chemotherapy and immunotherapy, as well as tailor surveillance protocol for individual patients.

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