Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China; Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
Cancer Lett. 2024 Apr 28;588:216778. doi: 10.1016/j.canlet.2024.216778. Epub 2024 Mar 6.
This study aims to investigate applicable robust biomarkers that can improve prognostic predictions for colorectal liver metastasis (CRLM) patients receiving simultaneous resection. A total of 1323 CRLM patients from multiple centres were included. The preoperative aspartate aminotransferase to platelet ratio index (APRI) level from blood of patients were obtained. Patients were stratified into a high APRI group and a low APRI group, and comparisons were conducted by analyzing progression-free survival (PFS), overall survival (OS) and postoperative early recurrence. Tumour samples of CRLM were collected to perform single-cell RNA sequencing and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) to investigate the association of APRI levels and the tumour microenvironment of CRLM. Compared with APRI <0.33, PFS disadvantage (IPTW-adjusted HR = 1.240, P = 0.015) and OS disadvantage (IPTW- adjusted HR = 1.507, P = 0.002) of APRI ≥0.33 were preserved in the IPTW-adjusted Cox hazards regression analyses. An APRI ≥0.25 was associated with a significantly increased risk of postoperative early recurrence after adjustment (IPTW-adjusted OR = 1.486, P = 0.001). The external validation showed consistent results with the training cohort. In the high APRI group, the single-cell RNA sequencing results revealed a heightened malignancy of epithelial cells, the enrichment of inflammatory-like cancer-associated fibroblasts and SPP1 macrophages associated with activation of malignant cells and fibrotic microenvironment, and a more suppressed-function T cells; mIHC/IF showed that PD1 CD4 T cells, FOXP3 CD4 T cells, PD1 CD8 T cells, FOXP3 CD8 T cells, SPP1 macrophages and iCAFs were significantly increased in the intratumoral region and peritumoral region. This study contributed valuable evidence regarding preoperative APRI for predicting prognoses among CRLM patients receiving simultaneous resection and provided underlying clues supporting the association between APRI and clinical outcomes by single-cell sequencing bioinformatics analysis and mIHC/IF.
本研究旨在探讨适用于同时接受切除术的结直肠癌肝转移（CRLM）患者的预后预测的稳健生物标志物。共纳入了来自多个中心的 1323 名 CRLM 患者。从患者的血液中获得术前天门冬氨酸氨基转移酶与血小板比值指数（APRI）水平。患者被分为高 APRI 组和低 APRI 组，并通过分析无进展生存期（PFS）、总生存期（OS）和术后早期复发来进行比较。收集 CRLM 的肿瘤样本进行单细胞 RNA 测序和多重免疫组化/免疫荧光（mIHC/IF），以研究 APRI 水平与 CRLM 肿瘤微环境的关联。与 APRI<0.33 相比，APRI≥0.33 的 PFS 劣势（IPTW 调整 HR=1.240，P=0.015）和 OS 劣势（IPTW 调整 HR=1.507，P=0.002）在 IPTW 调整的 Cox 风险回归分析中得以保留。APRI≥0.25 与调整后术后早期复发的风险显著增加相关（IPTW 调整 OR=1.486，P=0.001）。外部验证结果与训练队列一致。在高 APRI 组中，单细胞 RNA 测序结果显示上皮细胞的恶性程度增加，炎症样癌症相关成纤维细胞和 SPP1 巨噬细胞富集，与恶性细胞和纤维性微环境的激活有关，以及功能受抑的 T 细胞更多；mIHC/IF 显示 PD1 CD4 T 细胞、FOXP3 CD4 T 细胞、PD1 CD8 T 细胞、FOXP3 CD8 T 细胞、SPP1 巨噬细胞和 iCAFs 在肿瘤内和肿瘤周围区域明显增加。本研究为同时接受切除术的 CRLM 患者的术前 APRI 预测预后提供了有价值的证据，并通过单细胞测序生物信息学分析和 mIHC/IF 为 APRI 与临床结果之间的关联提供了潜在的线索。
