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Dickkopf-4 gene expression is associated with differentiation and lymph node metastasis in colorectal cancer.

ABSTRACT: Background and Aim:Although high expression of Dickkopf-4 (DKK-4) in colorectal cancer has been reported in previous studies, its impact on clinicopathological features, including the prognosis and mechanism of expression, has not been well clarified to date. Methods:(i) DKK-4 protein expression was analyzed by immunohistochemical staining with anti-DKK-4 antibody using archived formalin-fixed paraffin-embedded specimens obtained at surgery from 122 patients with colorectal cancer, and its association with clinicopathological findings was also investigated. (ii) The association between intratumoral DKK-4 protein expression and somatic hotspot mutations in cancer-associated genes in 40 patients was investigated using a next-generation sequencer. Results:In cross-section, DKK-4 protein expression in colorectal tissue was related to an adenocarcinoma of a histologically differentiated type (tub1/tub2, P?=?0.032) and distant metastasis (P?=?0.012). Longitudinally, however, DKK-4 was not an independent prognostic factor determining overall survival (OS). On the other hand, in patients with metastasis, high DKK-4 protein was independently associated with short OS (P?=?0.013). In addition, colorectal cancer tissue with high DKK-4 protein expression was associated with hotspot mutations in Wnt/? catenin-signaling molecules (APC, CTNNB1, and FBXW7, P?=?0.03). Conclusion:Intratumoral DKK-4 expression, by partly reflecting the Wnt/? catenin pathway, is strongly associated with the advancement of colorectal cancer and OS in colorectal cancer patients with metastasis, although further studies are needed.

SUBMITTER: Tsukui Y

PROVIDER: S-EPMC6788377 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Dickkopf-4 gene expression is associated with differentiation and lymph node metastasis in colorectal cancer.

Tsukui Yuya Y Yamaguchi Tatsuya T Maekawa Shinya S Takano Shinichi S Sato Tadashi T Enomoto Nobuyuki N

JGH open : an open access journal of gastroenterology and hepatology 20190410 5

<h4>Background and aim</h4>Although high expression of Dickkopf-4 (DKK-4) in colorectal cancer has been reported in previous studies, its impact on clinicopathological features, including the prognosis and mechanism of expression, has not been well clarified to date.<h4>Methods</h4>(i) DKK-4 protein expression was analyzed by immunohistochemical staining with anti-DKK-4 antibody using archived formalin-fixed paraffin-embedded specimens obtained at surgery from 122 patients with colorectal cancer ...[more]

PMID: 31633047

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Project description: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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Dickkopf-4 gene expression is associated with differentiation and lymph node metastasis in colorectal cancer.

Publications

Dickkopf-4 gene expression is associated with differentiation and lymph node metastasis in colorectal cancer.

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