Influence of the duration of type 2 diabetes mellitus on colorectal cancer outcomes

Abstract Type 2 diabetes mellitus (T2DM) is a progressive disease, which affects colorectal cancer (CRC) survival. However, data on the relationship between CRC survival and T2DM duration is scarce and controversial. A retrospective observational study was conducted. Sub-cohorts were created based on the duration of T2DM as follows, ≤ or > 5/10/15/20 years. 204 of the 817 (24.95%) included study participants had T2DM at any point of CRC. 160 of the 204 CRC + T2DM patients had detailed T2DM duration data. At the time of CRC diagnosis, 85, 50, 31, and 11 patients had T2DM for > 5/10/15/20 years, respectively, which increased to 110, 71, 45, and 17 during the course of the study. Despite constant glycated hemoglobin values throughout the study, shorter overall and disease-specific survival times were observed for the > 5/10/15 years cohorts and longitudinal survival modeling techniques confirmed the significant effect of T2DM duration in all cohorts. While in the first 3 years after CRC diagnosis, the best survival was found for the ≤ 5 years cohort, all diabetes cohorts had the same survival thereafter. T2DM duration affected CRC survival significantly, therefore, a closer follow-up of this sub-populations is suggested

Deconstructing Immune Cell Infiltration in Human Colorectal Cancer: A Systematic Spatiotemporal Evaluation

Cancer-related immunity has been identified as playing a key role in the outcome of colorectal cancer (CRC); however, the exact mechanisms are only partially understood. In this study, we evaluated a total of 242 surgical specimen of CRC patients using tissue microarrays and immunohistochemistry to evaluate tumor infiltrating immune cells (CD3, CD4, CD8, CD20, CD23, CD45 and CD56) and immune checkpoint markers (CTLA-4, PD-L1, PD-1) in systematically selected tumor regions and their corresponding lymph nodes, as well as in liver metastases. Additionally, an immune panel gene expression assay was performed on 12 primary tumors and 12 consecutive liver metastases. A higher number of natural killer cells and more mature B cells along with PD-1+ expressing cells were observed in the main tumor area as compared to metastases. A higher number of metastatic lymph nodes were associated with significantly lower B cell counts. With more advanced lymph node metastatic status, higher leukocyte—particularly T cell numbers—were observed. Eleven differentially expressed immune-related genes were found between primary tumors and liver metastases. Also, alterations of the innate immune response and the tumor necrosis factor superfamily pathways had been identified