Related Experiment Video
Updated: Sep 2, 2025
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
Alteration in the Immune Microenvironment Based on APC Status in MSS/pMMR Colon Cancer
1Cancer Centre, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Introduction:
Immunotherapy is currently the most promising antitumor treatment approach. However, the colon cancer immunotherapy indication dMMR/MSI-H do not cover all colon cancer patients suitable for immunotherapy. We performed transcriptome-wide expression profile analyses of pMMR/MSS colon adenocarcinoma (COAD) specimens from TCGA database to identify a genetype signature associated with tumor immune microenvironment types (TIMTs).
Methods:
TCGA database was used to identify tumor genotypes suitable for antitumor immunotherapy. We analyzed RNA-sequencing profiles of 338 COAD targeted to the pMMR/MSS group from TCGA public dataset. The ESTIMATE and the CIBERSORT were used to analyze the pMMR/MSS COAD immune microenvironment between APC wild and APC mutation. Furthermore, we further verified the relationship between APC genotype and TIMTs and the efficacy of immunotherapy in 42 colon cancer specimens.
Results:
We identified that in APC-wt/MSS colon cancer, the expressions of PD-1, PD-L1, CTLA4, and CYT (GZMA and PRF1) were increased. The TMB, Immunoscore, and the proportion of CT8+ T cell infiltration also were identified increasing in these patients. And pathway enrichment analysis for differentially expressed genes (DEGs) between APC-wt and APC-mt MSS COAD was done to further explore their biological function. Similarly, the significant pathways for DEGs were mainly enriched in the immune response, extracellular matrix, and cell adhesion which involved in immune response. Specimens from 42 colon cancer patients, including 22 APC-mt/MSS and 20 APC-wt/MSS, were immunohistochemically evaluated for expression of CD8 and PD-L1. And APC-wt/MSS tumors showed significantly higher expression of CD8 and PD-L1 than APC-mt/MSS tumor. Moreover, APC-wt was compared with APC-mt MSS/pMMR colon cancer (DOR, 45% and 26.7%, respectively; P < 0.05).
Conclusion:
Based on the results, we found that more colon cancers of APC-wt/MSS are classified by TMIT I. And APC-wt/MSS colon cancer patients are more likely to benefit from antitumor immunotherapy.
Insights
Colon cancer patients with wild-type APC and microsatellite stability (APC-wt/MSS) show increased immune cell infiltration and may benefit more from immunotherapy. This finding expands immunotherapy eligibility beyond dMMR/MSI-H markers.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immunotherapy is a promising cancer treatment, but current indicators like mismatch repair deficiency/microsatellite instability-high (dMMR/MSI-H) do not identify all suitable colon cancer patients.
- Identifying novel biomarkers for immunotherapy response in colon cancer is crucial for expanding treatment eligibility.
Purpose of the Study:
- To analyze transcriptome-wide expression profiles of proficient mismatch repair/microsatellite stable (pMMR/MSS) colon adenocarcinoma (COAD) specimens.
- To identify genotype signatures associated with tumor immune microenvironment types (TIMTs) in pMMR/MSS COAD.
- To evaluate the potential of APC genotype as a predictor of immunotherapy response in colon cancer.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for RNA-sequencing data of 338 pMMR/MSS COAD patients.
- Employed ESTIMATE and CIBERSORT algorithms to analyze immune microenvironments based on APC wild-type (APC-wt) versus APC mutation (APC-mt).
- Conducted immunohistochemical evaluation of CD8 and PD-L1 expression in 42 colon cancer specimens to validate findings.
Main Results:
- APC-wt/MSS colon cancer exhibited increased expression of immune markers (PD-1, PD-L1, CTLA4, GZMA, PRF1), higher tumor mutational burden (TMB), and greater CD8+ T cell infiltration compared to APC-mt/MSS.
- Pathway enrichment analysis revealed immune response, extracellular matrix, and cell adhesion pathways were significantly altered in APC-wt vs. APC-mt MSS COAD.
- APC-wt/MSS tumors demonstrated significantly higher CD8 and PD-L1 expression, correlating with better response rates (45% vs. 26.7%) in immunotherapy.
Conclusions:
- APC-wt/MSS colon cancer patients are more likely to be classified under favorable TIMT I and may derive greater benefit from immunotherapy.
- The APC genotype serves as a potential predictive biomarker for immunotherapy response in MSS colon cancer, expanding treatment possibilities.
- These findings suggest a broader application of immunotherapy in colon cancer beyond the established dMMR/MSI-H criteria.
More Related Videos
05:21Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
08:51Murine Appendectomy Model of Chronic Colitis Associated Colorectal Cancer by Precise Localization of Caecal Patch
Published on: August 24, 2019
Related Concept Videos
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
02:23Abnormal Proliferation
02:17The Tumor Microenvironment