Next‑generation sequencing reveals lymph node metastasis associated genetic markers in colorectal cancer

Xie,Ni; Yao,Yujiang; Wan,Lili; Zhu,Ting; Liu,Litao; Yuan,Jianhui

doi:10.3892/etm.2017.4464

Next‑generation sequencing reveals lymph node metastasis associated genetic markers in colorectal cancer

Authors:
- Ni Xie
- Yujiang Yao
- Lili Wan
- Ting Zhu
- Litao Liu
- Jianhui Yuan
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Affiliations: 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
Published online on: May 17, 2017 https://doi.org/10.3892/etm.2017.4464
Pages: 338-343

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Abstract

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.

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