Research Paper Volume 13, Issue 16 pp 20609—20628
Intravascular emboli relates to immunosuppressive tumor microenvironment and predicts prognosis in stage III colorectal cancer
- 1 Department of General Surgery, Xiangya Hospital, Central South University, Changsha, P.R. China
- 2 Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha, P.R. China
- 3 Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, P.R. China
- 4 The National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, P.R. China
Received: January 4, 2021 Accepted: July 21, 2021 Published: August 26, 2021
https://doi.org/10.18632/aging.203451How to Cite
Copyright: © 2021 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Stage III colorectal cancer (CRC) patients experience varying degrees of prognosis even if receiving standard therapeutic regimes. Intravascular emboli (IVE), a type of vascular invasion, impacts the clinical outcome in CRC. In this study, we confirmed the role of IVE in predicting the prognosis of stage III CRC patients and characterized the tumor microenvironment (TME) of CRC with IVE.
Methods: Data from 220 consecutive patients (cohort 1) with stage III CRC undergoing radical surgery was collected retrospectively between January 2009 to December 2014. According to the presence of IVE, which was confirmed by two independent pathologists, patients were classified into two groups. Univariate and multivariate Cox regression analyses were performed to evaluate the relation of IVE presence to patients’ prognosis. The association between IVE and clinicopathological factors was also analyzed. Furthermore, differentially expressed genes (DEGs) and gene set enrichment analyses (GSEA) were performed to describe features of the TME based on microarray data consisting of 6 patients. Tumor tissues from a separate cohort of 73 patients with stage III CRC (cohort 2) collected between June 2014 and December 2015 were used to analyze tumor-infiltrating lymphocyte (TIL) by immunohistochemistry (IHC) staining.
Results: IVE was observed in 126 (57.3%) patients and could serve as an unfavorable independent prognostic predictor (P < 0.001) as well as lymph node metastasis (P < 0.05) and tumor location (P < 0.05). Additionally, patients with IVE had a higher neutrophil percentage (P = 0.002) and lower lymphocyte percentage (P = 0.002) relative to those without IVE. CRC with IVE had a significantly different profile of DEGs compared to CRC without IVE, and GSEA showed chronic inflammatory and immunosuppressive TME may promote IVE development. In cohort 2, tumors with IVE had fewer CD3+ TILs in the stromal region, as well as fewer CD8+ TILs in both stromal and tumoral regions relative to those without IVE.
Conclusion: IVE, which was related closely to a chronic inflammatory and immunosuppressive TME, forecasted a worse prognosis of stage III CRC patients and may be taken into consideration when a therapeutic strategy is decided upon.