Hu Xiang, Li Ya-Qi, Ma Xiao-Ji, Zhang Long, Cai San-Jun, Peng Jun-Jie
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Oncol. 2019 Aug 13;9:704. doi: 10.3389/fonc.2019.00704. eCollection 2019.
In order to accurately predict oncological outcomes of colorectal cancer (CRC), we established a risk signature with tumor infiltrating neutrophils and T immune cells for prognosis. A total of 276 CRC patients from FUSCC, and 434 patients from TCGA cohort were enrolled in the study. A risk signature model in combination with CEACAM8+ neutrophils, CD3+, CD8+ T lymphocytes, and FOXP3+ regulatory T cells was established, and the relationships with patient clinicopathological characteristics and prognosis were evaluated. In TCGA cohort, high CEACAM8 expression was observed as an independent factor of poor disease-free survival (DFS), as well as inversely correlated with CD8 ( = 0.0035) and FOXP3 expression ( = 0.05). In the FUSCC cohort for validation, the association between CEACAM8+ neutrophils and DFS had been confirmed in CRC tissue ( = 0.026). Furthermore, a risk stratification was derived from integration of CEACAM8+ neutrophils and T immune cells. In both OS and DFS, the high-risk group all demonstrated worse prognosis than low-risk group, with statistical significance (all < 0.001). In addition, the high-risk group was correlated with post-operative relapses with accurate prediction. Furthermore, the high-risk group identified a subgroup of CRC patients who appeared not to benefit from adjuvant chemotherapy. At last, predictive nomograms were constructed with recognized independent prognosticators, showing this risk signature increasing the predictive accuracy and efficiency for OS and DFS. In conclusion, incorporation of neutrophil into T lymphocytes could provide more accurate prognostic information in CRC, and this risk stratification predicted for survival benefit from post-operative chemotherapy.
为了准确预测结直肠癌（CRC）的肿瘤学结局，我们建立了一种基于肿瘤浸润中性粒细胞和T免疫细胞的风险特征用于预后评估。本研究纳入了来自复旦大学附属肿瘤医院的276例CRC患者以及来自TCGA队列的434例患者。建立了一个结合CEACAM8⁺中性粒细胞、CD3⁺、CD8⁺ T淋巴细胞和FOXP3⁺调节性T细胞的风险特征模型，并评估了其与患者临床病理特征及预后的关系。在TCGA队列中，观察到高CEACAM8表达是无病生存期（DFS）差的独立因素，且与CD8表达呈负相关（r = 0.0035），与FOXP3表达也呈负相关（r = 0.05）。在用于验证的复旦大学附属肿瘤医院队列中，CRC组织中CEACAM8⁺中性粒细胞与DFS之间的关联得到了证实（r = 0.026）。此外，通过整合CEACAM8⁺中性粒细胞和T免疫细胞得出了一种风险分层。在总生存期（OS）和DFS方面，高危组的预后均明显差于低危组，具有统计学意义（均P < 0.001）。此外，高危组与术后复发相关且预测准确。再者，高危组识别出了一组似乎无法从辅助化疗中获益的CRC患者亚组。最后，利用公认的独立预后因素构建了预测列线图，表明该风险特征提高了OS和DFS的预测准确性和效率。总之，将中性粒细胞纳入T淋巴细胞可在CRC中提供更准确的预后信息，且这种风险分层可预测术后化疗的生存获益。
