Xie Ni, Yao Yujiang, Wan Lili, Zhu Ting, Liu Litao, Yuan Jianhui
Science and Education Administration Department of Shenzhen Second People's Hospital, Shenzhen, Guangdong 518000, P.R. China.
Science and Education Administration Department of Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong 518055, P.R. China.
Exp Ther Med. 2017 Jul;14(1):338-343. doi: 10.3892/etm.2017.4464. Epub 2017 May 17.
Colorectal cancer is the third most prevalent type of cancer in the United States. Early diagnosis of lymph node metastases is essential to improve the prognosis for patients with colorectal cancer. Therefore, the present study aimed to screen genetic markers, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and mRNA expression, associated with lymph node metastases in patients with colorectal cancer to enable an early diagnosis. Targeted next-generation sequencing was applied to capture SNPs and CNVs in tumor-related candidate genes within tumor tissues from 39 colorectal cancer patients; reverse transcription-quantitative polymerase chain reaction was used to detect the specific mRNA level of tumor-related candidate genes, including vascular endothelial growth factor C, cyclin-A2, Interleukin-2, ATP-binding cassette sub-family G member 2, epidermal growth factor (EGF) and nuclear factor kappa B subunit 1 (NFKB1) on chromosome 4. The SNPs in solute carrier family 28 member 3 (SLC28A3), breast cancer 1 (BRCA1), ribonucleotide reductase regulators subunit M2 (RRM2), PMS1 homolog 2 (PMS2), cytidine deaminase (CDA), epoxide hydrolase 1 (EPHX1), heterogenous ribonucleoprotein particle-associated with lethal yellow (RALY), Siglec-3 (CD33), B cell lymphoma 10 (BCL10), ETS variant 1 (ETV1), macrophage stimulating 1 receptor 1 (MST1R), lysine methyltransferase 2B (KMT2B), B cell lymphoma 2 (BCL2), U6 small nuclear RNA-associated Sm-like protein 3 (LSM3), thyroid transcription factor 1 (TTF1) and mitogen-activated protein 3 kinase 1 (MAP3K1) were significantly associated with lymphatic metastasis (P<0.05). EGF and NFKB1 were both observed to be significantly downregulated in the lymph node metastases group (P<0.05). Although no association between CNVs and lymph node metastases in patients with colorectal cancer was observed in the present study, SNPs in SLC28A3, BRCA1, RRM2, PMS2, CDA, EPHX1, RALY, CD33, BCL10, ETV1, MST1R, KMT2B, BCL2, LSM3, TTF1 and MAP3K1 were significantly associated with colorectal cancer. Downregulation of EGF and NFKB1 was also identified to be associated with lymph node metastases in colorectal cancer. The findings of the current study provide a scientific basis for the clinical inspection of lymphatic metastasis and prognosis prediction, intervention and guidance therapy for patients with colorectal cancer.
结直肠癌是美国第三大常见癌症类型。早期诊断淋巴结转移对于改善结直肠癌患者的预后至关重要。因此，本研究旨在筛选与结直肠癌患者淋巴结转移相关的遗传标记，包括单核苷酸多态性（SNP）、拷贝数变异（CNV）和mRNA表达，以便进行早期诊断。应用靶向二代测序技术捕获39例结直肠癌患者肿瘤组织中肿瘤相关候选基因的SNP和CNV；采用逆转录定量聚合酶链反应检测肿瘤相关候选基因的特异性mRNA水平，包括血管内皮生长因子C、细胞周期蛋白A2、白细胞介素-2、ATP结合盒亚家族G成员2、表皮生长因子（EGF）和4号染色体上的核因子κB亚基1（NFKB1）。溶质载体家族28成员3（SLC28A3）、乳腺癌1（BRCA1）、核糖核苷酸还原酶调节亚基M2（RRM2）、PMS1同源物2（PMS2）、胞苷脱氨酶（CDA）、环氧化物水解酶1（EPHX1）、与致死性黄色相关的异质性核糖核蛋白颗粒（RALY）、唾液酸结合免疫球蛋白样凝集素3（CD33）、B细胞淋巴瘤10（BCL10）、ETS变异体1（ETV1）、巨噬细胞刺激1受体1（MST1R）、赖氨酸甲基转移酶2B（KMT2B）、B细胞淋巴瘤2（BCL2）、U6小核RNA相关Sm样蛋白3（LSM3）、甲状腺转录因子1（TTF1）和丝裂原活化蛋白3激酶1（MAP3K1）中的SNP与淋巴转移显著相关（P<0.05）。在淋巴结转移组中观察到EGF和NFKB1均显著下调（P<0.05）。尽管本研究未观察到结直肠癌患者CNV与淋巴结转移之间的关联，但SLC28A3、BRCA1、RRM2、PMS2、CDA、EPHX1、RALY、CD33、BCL10、ETV1、MST1R、KMT2B、BCL2、LSM3、TTF1和MAP3K1中的SNP与结直肠癌显著相关。还发现EGF和NFKB1的下调与结直肠癌的淋巴结转移有关。本研究结果为结直肠癌患者淋巴转移的临床检查、预后预测、干预及指导治疗提供了科学依据。
