Department of Medical Cell Biology, Uppsala University, Uppsala 75123, Sweden.
Department of Surgery, Region Jönköping County, Jönköping 55305, Sweden.
World J Gastroenterol. 2021 Aug 14;27(30):5076-5087. doi: 10.3748/wjg.v27.i30.5076.
Leukocytes, such as T cells and macrophages, play an important role in tumorigenesis. CC chemokine ligand (CCL) 4, which is produced by lymphocytes and macrophages, has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes.
To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer (CRC) and evaluate their prognostic significance.
Luminex technology was used to determine CCL4 Levels in CRC tissue ( = 98), compared with paired normal tissue, and in plasma from patients with CRC ( = 103), compared with healthy controls ( = 97). Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery, Ryhov County Hospital, Jönköping, Sweden. Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue ( = 101). Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls.
The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue (90%, < 0.001 and 45%, < 0.05, respectively). CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease. Low CCL4 protein expression levels in CRC tissue were associated with a 30% lower cancer-specific survival rate in patients ( < 0.01). The level of plasma CCL4 was 11% higher in CRC patients than in healthy controls ( < 0.05) and was positively correlated ( = 0.56, < 0.01) with the CCL4 protein level in CRC tissue. The analysis of CCL4 gene polymorphism rs10491121 showed a difference ( < 0.05) between localized disease and disseminated disease in the right colon, with a dominance of allele A in localized disease. Moreover, the rate of the A allele was higher among CRC patients with mucinous cancer than among those with non-mucinous cancer.
The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121, particularly in the right colon, are associated with clinical outcome in CRC patients.
白细胞，如 T 细胞和巨噬细胞，在肿瘤发生中发挥重要作用。CC 趋化因子配体（CCL）4 由淋巴细胞和巨噬细胞产生，已在胃肠道黏膜中发现表达，是各种白细胞的有效趋化因子。
检查结直肠癌（CRC）患者 CCL4 表达及其遗传多态性 rs10491121，并评估其预后意义。
使用 Luminex 技术测定 CRC 组织中 CCL4 水平（=98），与配对的正常组织进行比较，并测定 CRC 患者血浆中 CCL4 水平（=103），与健康对照者（=97）进行比较。纳入的患者于 1996 年至 2019 年期间在瑞典延雪平 Ryhov 县医院外科接受了原发性结直肠腺癌的手术切除。采用逆转录定量 PCR 检测 CRC 组织中的 CCL4 基因表达（=101）。采用 TaqMan 单核苷酸多态性检测试剂盒检测 610 例 CRC 患者和 409 例健康对照者的 CCL4 rs10491121 多态性。
CRC 组织中的 CCL4 蛋白和信使 RNA 表达水平高于配对的正常组织（90%，<0.001 和 45%，<0.05）。局限疾病患者的 CRC 组织中的蛋白表达水平比播散性疾病患者高 2.8 倍。CRC 组织中 CCL4 蛋白低表达与患者癌症特异性生存率降低 30%（<0.01）相关。CRC 患者的血浆 CCL4 水平比健康对照者高 11%（<0.05），并与 CRC 组织中的 CCL4 蛋白水平呈正相关（=0.56，<0.01）。CCL4 基因多态性 rs10491121 分析显示，右结肠癌中局限疾病与播散性疾病之间存在差异（<0.05），局灶性疾病中等位基因 A 占优势。此外，CCL4 基因多态性 rs10491121 分析显示，黏液腺癌患者的 A 等位基因发生率高于非黏液腺癌患者。
本研究表明，CRC 组织中的 CCL4 水平和 CCL4 基因多态性 rs10491121，特别是在右结肠癌中，与 CRC 患者的临床结局相关。
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