Association of preoperative aspartate aminotransferase to platelet ratio index with outcomes and tumour microenvironment among colorectal cancer with liver metastases

被引：5

作者：

Chen, Qichen ^{[1
,2
]}

Deng, Yiqiao ^{[2
]}

Li, Yuan ^{[1
]}

Chen, Jinghua ^{[2
]}

Zhang, Rui ^{[3
]}

Yang, Lang ^{[2
]}

Guo, Rui ^{[4
]}

Xing, Baocai ^{[4
]}

Ding, Peirong ^{[1
]}

Cai, Jianqiang ^{[2
]}

Zhao, Hong ^{[2
]}

机构：

[1] Sun Yat Sen Univ, Canc Ctr, Guangdong Prov Clin Res Ctr Canc, State Key Lab Oncol South China,Dept Colorectal Su, Guangzhou 510060, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Natl Clin Res Ctr Canc, Dept Hepatobiliary Surg,Canc Hosp, Beijing 100021, Peoples R China

[3] China Med Univ, Liaoning Canc Hosp & Inst, Canc Hosp, Dept Colorectal Surg, Shenyang, Peoples R China

[4] Peking Univ, Beijing Canc Hosp & Inst, Sch Oncol, Key Lab Carcinogenesis & Translat Res,Hepatopancre, Beijing, Peoples R China

来源：

CANCER LETTERS | 2024年 / 588卷

基金：

中国国家自然科学基金;

关键词：

Colorectal liver metastasis; Preoperative APRI; Outcomes; Tumour microenvironment; Single -cell sequencing; Multiplex immunohistochemistry/immunofluorescence; RESECTION; FIBROSIS;

D O I：

10.1016/j.canlet.2024.216778

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：16