Clinicopathologic, genetic and immune cell infiltration analysis of colorectal signet ring cell carcinoma with comparison to conventional adenocarcinoma.
[OBJECTIVE] We sought to characterize the genomic and immune landscape of signet ring cell carcinoma (SRCC), a rare and aggressive subtype of colorectal cancer (CRC).
APA
An Y, Zhou J, et al. (2026). Clinicopathologic, genetic and immune cell infiltration analysis of colorectal signet ring cell carcinoma with comparison to conventional adenocarcinoma.. Journal of the National Cancer Center, 6(1), 30-39. https://doi.org/10.1016/j.jncc.2025.06.006
MLA
An Y, et al.. "Clinicopathologic, genetic and immune cell infiltration analysis of colorectal signet ring cell carcinoma with comparison to conventional adenocarcinoma.." Journal of the National Cancer Center, vol. 6, no. 1, 2026, pp. 30-39.
PMID
41738041
Abstract
[OBJECTIVE] We sought to characterize the genomic and immune landscape of signet ring cell carcinoma (SRCC), a rare and aggressive subtype of colorectal cancer (CRC).
[METHODS] Tissue samples and clinicopathological data were retrospectively analyzed from 37 SRCC and 172 conventional adenocarcinomas (AC) of rectum and sigmoid colon. The genetic and immune profiles were assessed using DNA next-generation sequencing (NGS) and multiplex immunohistochemistry.
[RESULTS] Compared to AC, SRCC patients were younger, had higher tumor, node, metastasis (TNM) stages and tumor grades (all < 0.05), and exhibited significantly worse 3-year disease-free survival (DFS) and overall survival (OS) (both < 0.0001). SRCC exhibited fewer somatic mutations in well-known CRC driver genes including (32 % vs. 74 %), (16 % vs. 42 %), and (0 vs. 20 %), but showed higher frequencies of genetic alterations in (present only in SRCC), , and (all < 0.05). SRCC showed significantly higher levels of CD8 tumor-infiltrating lymphocytes (TILs), but lower PD-1CD8 TILs in both stroma and intratumoral regions (all < 0.05). Interestingly, high PD-1CD8 TILs in intratumoral regions significantly predicted longer DFS and OS in all SRCC and stage II-III SRCC patients (all < 0.05), while CD3 or CD8 TILs did not. Moreover, the characteristic immune cell infiltration correlated with specific genetic alterations in SRCC.
[CONCLUSIONS] Colorectal SRCC is a clinically and molecularly distinct and highly malignant subtype compared to AC. It exhibits a "pseudo-T cell-inflamed" tumor microenvironment with increased total CD8 TILs but reduced PD-1CD8 TIL infiltration. Notably, PD-1CD8 TIL infiltration is associated with favorable prognosis. These findings provide new insights into tumor-immune interactions in SRCC, with potential implications for prognostic stratification and the development of personalized immunotherapeutic strategies.
[METHODS] Tissue samples and clinicopathological data were retrospectively analyzed from 37 SRCC and 172 conventional adenocarcinomas (AC) of rectum and sigmoid colon. The genetic and immune profiles were assessed using DNA next-generation sequencing (NGS) and multiplex immunohistochemistry.
[RESULTS] Compared to AC, SRCC patients were younger, had higher tumor, node, metastasis (TNM) stages and tumor grades (all < 0.05), and exhibited significantly worse 3-year disease-free survival (DFS) and overall survival (OS) (both < 0.0001). SRCC exhibited fewer somatic mutations in well-known CRC driver genes including (32 % vs. 74 %), (16 % vs. 42 %), and (0 vs. 20 %), but showed higher frequencies of genetic alterations in (present only in SRCC), , and (all < 0.05). SRCC showed significantly higher levels of CD8 tumor-infiltrating lymphocytes (TILs), but lower PD-1CD8 TILs in both stroma and intratumoral regions (all < 0.05). Interestingly, high PD-1CD8 TILs in intratumoral regions significantly predicted longer DFS and OS in all SRCC and stage II-III SRCC patients (all < 0.05), while CD3 or CD8 TILs did not. Moreover, the characteristic immune cell infiltration correlated with specific genetic alterations in SRCC.
[CONCLUSIONS] Colorectal SRCC is a clinically and molecularly distinct and highly malignant subtype compared to AC. It exhibits a "pseudo-T cell-inflamed" tumor microenvironment with increased total CD8 TILs but reduced PD-1CD8 TIL infiltration. Notably, PD-1CD8 TIL infiltration is associated with favorable prognosis. These findings provide new insights into tumor-immune interactions in SRCC, with potential implications for prognostic stratification and the development of personalized immunotherapeutic strategies.
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