He Jiahua, Li Weihao, Wang Jiayu, Wu Xiaojun, Zhang Weili, Lin Junzhong, Xiao Binyi, Yu Long, Liao Leen, Wang Song, Wang Weifeng, Lin Yuguang, Hong Xuanlin, Xing Yue, Pan Zhizhong, Peng Jianhong
Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, Guangdong, People's Republic of China.
Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
Clin Transl Oncol. 2025 Apr;27(4):1681-1694. doi: 10.1007/s12094-024-03720-0. Epub 2024 Sep 13.
Monocarboxylate transporter 4 (MCT4) is a novel biomarker related to the level of immune cell infiltration, but its impact on tumor immune microenvironment (TIME) of colorectal liver oligometastases (CLO) remains unclear. The aim of this study was to assess MCT4 expression in primary tumor and liver oligometastases, investigate its impact on immune cell infiltration and its prognostic value for CLO patients undergoing liver resection.
We retrospectively selected 135 CLO patients who underwent curative liver resection between June 1999 and December 2016, and samples included 74 primary tumor tissues and 122 liver metastases. Immunohistochemistry (IHC) was performed to detect MCT4 expression in paraffin-embedded specimens and tyramine signal amplification (TSA) was used to detect the density of tumor-infiltrating lymphocytes, including CD3 + , CD8 + and Foxp3 + . Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test, and independent prognostic factors were identified with Cox regression modeling.
Survival analysis indicated that CLO patients with low MCT4 expression had better 3-year RFS and 3-year OS rates than those with high MCT4 expression. Multivariate analysis indicated that high MCT4 expression was independently associated with poor RFS and OS. High MCT4 expression was associated with a lower number of intratumoral CD3 + /CD8 + T cells and was associated with higher Foxp3 + T cells infiltration. Patients with low MCT4 expression and high levels of differential immune infiltration had longer survival.
MCT4 overexpression was associated with an unfavorable prognosis in patients with CLO and MCT4 expression level had an impact on intratumoral immune infiltration degree. A novel parameter that combined MCT4 expression level and differential immune infiltration level was constructed to stratify patients with CLO into different risk groups.
单羧酸转运蛋白4（MCT4）是一种与免疫细胞浸润水平相关的新型生物标志物，但其对结直肠肝寡转移（CLO）肿瘤免疫微环境（TIME）的影响尚不清楚。本研究旨在评估MCT4在原发性肿瘤和肝寡转移中的表达，探讨其对免疫细胞浸润的影响及其对接受肝切除的CLO患者的预后价值。
我们回顾性选择了1999年6月至2016年12月期间接受根治性肝切除的135例CLO患者，样本包括74例原发性肿瘤组织和122例肝转移灶。采用免疫组织化学（IHC）检测石蜡包埋标本中MCT4的表达，并采用酪胺信号放大（TSA）检测肿瘤浸润淋巴细胞的密度，包括CD3 +、CD8 +和Foxp3 +。采用Kaplan-Meier法和对数秩检验分析无复发生存期（RFS）和总生存期（OS），并通过Cox回归模型确定独立预后因素。
生存分析表明，MCT4低表达的CLO患者3年RFS和3年OS率均高于MCT4高表达患者。多因素分析表明，MCT4高表达与RFS和OS不良独立相关。MCT4高表达与肿瘤内CD3 + / CD8 + T细胞数量减少有关，与Foxp3 + T细胞浸润增加有关。MCT4低表达且免疫浸润差异水平高的患者生存期更长。
MCT4过表达与CLO患者预后不良相关，MCT4表达水平对肿瘤内免疫浸润程度有影响。构建了一个结合MCT4表达水平和免疫浸润差异水平的新参数，将CLO患者分为不同风险组。
