Abstract
Tumor-infiltrating immune cells (TIICs) play essential roles in cancer development and progression. However, the association of TIICs with prognosis in colorectal cancer (CRC) patients remains elusive. Infiltration of TIICs was assessed using ssGSEA and CIBERSORT tools. The association of TIICs with prognosis was analyzed in 1,802 CRC data downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) and TCGA (https://portal.gdc.cancer.gov/) databases. Three populations of TIICs, including CD66b+ tumor-associated neutrophils (TANs), FoxP3+ Tregs, and CD163+ tumor-associated macrophages (TAMs) were selected for immunohistochemistry (IHC) validation analysis in 1,008 CRC biopsies, and their influence on clinical features and prognosis of CRC patients was analyzed. Prognostic models were constructed based on the training cohort (359 patients). The models were further tested and verified in testing (249 patients) and validation cohorts (400 patients). Based on ssGSEA and CIBERSORT analysis, the correlation between TIICs and CRC prognosis was inconsistent in different datasets. Moreover, the results with disease-free survival (DFS) and overall survival (OS) data in the same dataset also differed. The high abundance of TIICs found by ssGSEA or CIBERSORT tools can be used for prognostic evaluation effectively. IHC results showed that TANs, Tregs, TAMs were significantly correlated with prognosis in CRC patients and were independent prognostic factors (PDFS ≤ 0.001; POS ≤ 0.023). The prognostic predictive models were constructed based on the numbers of TANs, Tregs, TAMs (C-indexDFS&OS = 0.86; AICDFS = 448.43; AICOS = 184.30) and they were more reliable than traditional indicators for evaluating prognosis in CRC patients. Besides, TIICs may affect the response to chemotherapy. In conclusion, TIICs were correlated with clinical features and prognosis in patients with CRC and thus can be used as markers.
Highlights
Colorectal cancer (CRC) is the second leading cause of cancerrelated mortality [1]
The infiltration of four tumor-infiltrating immune cell (TIIC) including macrophages M2, neutrophils, and regulatory T cell (Treg) was significantly negatively correlated with prognosis of colorectal cancer (CRC) patients (P ≤ 0.001; Supplementary Figures 1F,G), and these TIICs were chosen for IHC validation with 1,008 CRC tumor tissues (Figure 2A)
The prognostic analysis revealed that CRC patients with a high density of infiltrating tumor-associated neutrophil (TAN) had a better prognosis, whereas those with a high number of infiltrating Tregs and tumor-associated macrophage (TAM) had shorter disease-free survival (DFS) and overall survival (OS) (Figure 2B; Supplementary Figure 2)
Summary
Colorectal cancer (CRC) is the second leading cause of cancerrelated mortality [1]. Some improvements have been made in diagnosis, chemoradiotherapy and surgery; morbidity and mortality of CRC remain high. The prognosis of patients with advanced tumors remains poorly understood [2]. The prognosis of CRC patients mainly depends on the tumor status and TNM stage at diagnosis [3]. None of these has independent prognostic value in CRC patients [4, 5]. It is necessary to develop predictive systems that can effectively predict the progression of the disease and the efficacy of chemotherapy in individual patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
