2024 年第 2 期 第 19 卷

免疫球蛋白G Fc段结合蛋白低表达与结肠腺癌预后指标的相关性研究

Correlation between low expression of IgG Fc binding protein and prognostic indicators of colon adenocarcinoma

作者：贺苗1王琦2孙星2徐全晓1

英文作者：He Miao1 Wang Qi2 Sun Xing2 Xu Quanxiao1

单位：1河南省南阳市第一人民医院肿瘤内科河南省肿瘤分子生物学医学重点实验室，南阳473000；2河南省南阳市中心医院肿瘤内科，南阳473000

英文单位：1Department of Oncology Nanyang First People′s Hospital Henan Province Key Laboratory of Tumor Molecular Biology Medicine of Henan Province Nanyang 473000 China; 2Department of Oncology Nanyang Central Hospital Henan Province Nanyang 473000 China

关键词：结肠腺癌；免疫球蛋白GFc段结合蛋白；肿瘤微环境；免疫浸润；预后

英文关键词：Colonadenocarcinoma;IgGFcbindingprotein;Tumormicroenvironment;Immuneinfiltration;Prognosis

• 摘要：

• 目的  探究免疫球蛋白G Fc段结合蛋白（FCGBP）低表达与结肠腺癌预后指标的相关性。方法  收集TCGA数据库和基因型组织表达数据库中记录结肠腺癌肿瘤组织数据的455例患者（观察组）和记录癌旁组织数据的41例患者（对照组）。以FCGBP表达水平中间值（6.126 TPM）为标准，将观察组患者分为FCGBP高表达组（228例）和FCGBP低表达组（227例）。剔除失访患者后，按照“是否发生转移”将观察组患者分为转移组（52例）和非转移组（333例）。比较FCGBP高表达组和FCGBP低表达组患者的一般资料，比较观察组和对照组FCGBP mRNA的表达水平，比较转移组、非转移组与对照组FCGBP mRNA的表达水平。采用Log-rank检验绘制Kaplan-Meier曲线对转移组和非转移组患者进行生存分析，采用Cox回归方法分析评估FCGBP基因的表达在结肠腺癌中的预后价值。对FCGBP基因的表达情况和免疫细胞浸润水平进行Spearman相关性分析并绘图。结果  FCGBP高表达组中浸润深度为T3~T4、临床分期为Ⅲ~Ⅳ期、淋巴结转移和远处转移的比例均低于FCGBP低表达组，FCGBP高表达组中浸润深度为T1~T2和临床分期为Ⅰ~Ⅱ期的比例均高于FCGBP低表达组，差异均有统计学意义（均P<0.05）。转移组和非转移组FCGBP相对表达量均低于对照组［（5.0±2.1）TPM、（5.9±2.1）TPM比（9.5±1.0）TPM］，转移组低于非转移组，差异均有统计学意义（均P＜0.05）。Kaplan-Meier生存分析结果表明转移组的中位生存期低于非转移组（2.1年比8.2年），差异具有统计学意义（Log-rank P＜0.001）。Cox回归方法分析表明FCGBP表达水平越低，患者的总生存期越短，预后越差（风险比=4.434，95%置信区间：2.778～7.077，P＜0.001）。Spearman相关性分析结果表明结肠腺癌患者的FCGBP基因的表达与B淋巴细胞、CD+4 T细胞、CD+8 T细胞、中性粒细胞和树突状细胞的浸润水平呈正相关（均P<0.05）。结论  低水平FCGBP mRNA与结肠腺癌患者不良预后有关，并且与结肠腺癌患者肿瘤免疫浸润情况关系密切，有望成为结肠腺癌预后的生物标志物。

• Objective  To investigate the correlation between the low expression of IgG Fc binding protein (FCGBP) and the prognostic indicators of colon adenocarcinoma. Methods  A total of 455 patients with colon adenocarcinoma tumor tissue data (observation group) and 41 patients with paracancerous tissue data (control group) were collected from TCGA database and Genotype tissue expression database. Taking the middle value of FCGBP expression level (6.126 TPM) as the standard, the patients in the observation group were divided into FCGBP high expression group (228 cases) and FCGBP low expression group (227 cases). After excluding the patients who were lost to follow-up, the patients in the observation group were divided into the metastasis group (52 cases) and the non-metastasis group (333 cases) according to whether they had metastasis. The general datas of patients in the FCGBP high expression group and the FCGBP low expression group were compared, and the expression levels of FCGBP mRNA in the observation group and the control group were compared, and the expression levels of FCGBP mRNA in the metastasis group, the non-metastasis group and the control group were compared. Kaplan-Meier curve was drawn by Log-rank test to analyze the survival of patients in the metastasis group and the non-metastasis group. Cox regression analysis was used to evaluate the prognostic value of FCGBP gene expression in colon adenocarcinoma. The correlation between the expression of FCGBP gene and the level of immune cell infiltration was analyzed by Spearman correlation analysis and plotted. Results  The proportions of invasion depth of T3-T4, clinical stage of Ⅲ-Ⅳ, lymph node metastasis and distant metastasis in the FCGBP high expression group were lower than those in the FCGBP low expression group, the proportions of invasion depth of T1-T2 and clinical stage of Ⅰ-Ⅱ in the FCGBP high expression group were higher than those in the FCGBP low expression group (all P<0.05). The relative expression levels of FCGBP in the metastasis group and the non-metastasis group were lower than those in the control group ［(5.0±2.1)TPM, (5.9±2.1)TPM vs (9.5±1.0)TPM］, and the metastasis group was lower than the non-metastasis group (all P<0.05). Kaplan-Meier survival analysis showed that the median survival time of the metastasis group was lower than that of the non-metastasis group (2.1 years vs 8.2 years, Log-rank P<0.001). Cox regression analysis showed that the lower the expression level of FCGBP, the shorter the overall survival time and the worse the prognosis of patients (hazard ratio= 4.434, 95% confidence interval: 2.778-7.077, P<0.001). Spearman correlation analysis showed that the expression of FCGBP gene in patients with colon adenocarcinoma was positively correlated with the infiltration level of B lymphocytes, CD+4 T cells, CD+8 T cells, neutrophils and dendritic cells (all P<0.05). Conclusion  Low level of FCGBP mRNA is associated with poor prognosis of patients with colon adenocarcinoma, and is closely related to immune infiltration of colon adenocarcinoma, which is expected to be a prognostic biomarker of colon adenocarcinoma.