Journal of the National Cancer Center · 2025
Clinicopathologic, genetic and immune cell infiltration analysis of colorectal signet ring cell carcinoma with comparison to conventional adenocarcinoma.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
An Yang, Zhou Jiaolin, Su Lan, Cong Lin, Mao Xinxin, Chen Bo, Gong Yuhua, Xu Yaping, Chen Han, Wang Chentong, Lin Guole, Wu Huanwen
Аннотация
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 P < 0.05), and exhibited significantly worse 3-year disease-free survival (DFS) and overall survival (OS) (both P < 0.0001). SRCC exhibited fewer somatic mutations in well-known CRC driver genes including APC (32 % vs. 74 %), KRAS (16 % vs. 42 %), and FBXW7 (0 vs. 20 %), but showed higher frequencies of genetic alterations in SMAD4, RNF43, BCL2L11 (present only in SRCC), MYC, and ARID2 (all P < 0.05). SRCC showed significantly higher levels of CD8+ tumor-infiltrating lymphocytes (TILs), but lower PD-1+CD8+ TILs in both stroma and intratumoral regions (all P < 0.05). Interestingly, high PD-1+CD8+ TILs in intratumoral regions significantly predicted longer DFS and OS in all SRCC and stage II-III SRCC patients (all P < 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-1+CD8+ TIL infiltration. Notably, PD-1+CD8+ 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 P < 0.05), and exhibited significantly worse 3-year disease-free survival (DFS) and overall survival (OS) (both P < 0.0001). SRCC exhibited fewer somatic mutations in well-known CRC driver genes including APC (32 % vs. 74 %), KRAS (16 % vs. 42 %), and FBXW7 (0 vs. 20 %), but showed higher frequencies of genetic alterations in SMAD4, RNF43, BCL2L11 (present only in SRCC), MYC, and ARID2 (all P < 0.05). SRCC showed significantly higher levels of CD8+ tumor-infiltrating lymphocytes (TILs), but lower PD-1+CD8+ TILs in both stroma and intratumoral regions (all P < 0.05). Interestingly, high PD-1+CD8+ TILs in intratumoral regions significantly predicted longer DFS and OS in all SRCC and stage II-III SRCC patients (all P < 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-1+CD8+ TIL infiltration. Notably, PD-1+CD8+ 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.