DCLK1 immunoreactivity in colorectal neoplasia

Gagliardi, Giuseppe; Goswami, Monica; Passera, Roberto; Bellows, Charles F.

doi:10.2147/ceg.s30281

Cited by 57 publications

(63 citation statements)

References 23 publications

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“…In a subset of human colorectal cancers and high-grade adenomas strong Dclk1 protein expression is associated with disease recurrence but not with disease stage, suggesting that Dclk1 expression was an independent prognostic factor. 38,39 However, Dclk1 gene expression was significantly downregulated in a large number of colorectal cancer samples and cell lines, most likely through hypermethylation of the Dclk1 promoter. 40 Recently, Singh and colleagues were able to shed light on the complex epigenetic regulation of different Dclk1 transcripts in colorectal cancer, and showed that expression of a long Dclk1 isoform, transcribed from the 5' promoter, is silenced in colorectal cancer due to hypermethylation at this site.…”

Section: Functional Relevance Of Dclk1 Expression In Malignancymentioning

confidence: 99%

Functional implication of Dclk1 and Dclk1-expressing cells in cancer

2016

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Doublecortin like kinase protein 1 (Dclk1) is a microtubule-associated protein with C-terminal serine/threonine kinase domain. Originally designated Doublecortin and CaM kinase-like 1 protein (Dcamkl1) or KIAA0369, Dclk1 was first described as a marker for radial glia cells in the context of microtubule polymerization and neuronal migration, possibly contributing to early neurogenesis. Additionally, Dclk1 was proposed as a marker of quiescent gastrointestinal and pancreatic stem cells, but in recent years has been recognized as a marker for tuft cells in the gastrointestinal tract. While Dclk1C tuft cells are now considered as niche or sensory cells in the normal gut, growing evidence supports a role for Dclk1 function in a variety of malignancies, modulating the activity of multiple key pathways, including Kras signaling. Here, we review the recent advances in understanding of the importance of Dclk1 function in tumorigenesis and cancer.

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Section: Functional Relevance Of Dclk1 Expression In Malignancymentioning

confidence: 99%

Functional implication of Dclk1 and Dclk1-expressing cells in cancer

2016

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“…As a negative control, the primary antibody was replaced with serum immunoglobulin G (GTX35035; GeneTex, Inc., Irvine, CA, USA) at the same dilution. A CIA sample from the total cohort exhibiting strong intensity immunostaining for DCLK1, defined by the staining evaluation method of a previous study (13), was used as a positive control. For each specimen, at least five fields were viewed under a light microscope (magnification, x100; Olympus Corporation, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…The extent (or proportion) of DCLK1 staining was scored as: 0 (<5% positive cells), 1 (5-30% positive cells), 2 (31-60% positive cells) or 3 (61-100% positive cells); the staining intensity was scored as: 0 (negative), 1 (mild), 2 (moderate) or 3 (strong), as previously described (13). The final score was determined from the combination of the staining intensity and proportion scores.…”

Section: Methodsmentioning

confidence: 99%

“…Although the precise tumor-promoting mechanism of DCLK1 is yet to be determined, it has been demonstrated that reduced DCLK1 expression correlates with increased expression of tumor suppressor microRNAs (miRs), including miR-145, miR-200 and let-7a (11,12). Indeed, DCLK1 has been indicated to function as an oncogene in several types of tumor, including CRC (13)(14)(15), pancreatic cancer (8), hepatocellular carcinoma (16), gastric cancer (17) and Barrett's adenocarcinoma (18).…”

Section: Introductionmentioning

confidence: 99%

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Expression of doublecortin and CaM kinase‑like‑1 protein in serrated neoplasia of the colorectum

et al. 2017

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Abstract. The adenoma-carcinoma sequence (ACS) and the serrated pathway are two distinct developmental routes leading to the formation of colorectal carcinoma. Recently, the doublecortin and CaM kinase-like-1 protein (DCLK1) has been reported to serve as an intestinal cancer stem cell marker and has been demonstrated to be overexpressed through the ACS; however, there is a lack of reports on the role of DCLK1 in the serrated pathway. To clarify the correlation between DCLK1 protein expression and clinicopathological characteristics of the serrated tumorigenic pathway, the present study used immunohistochemistry to examine the expression of DCLK1 in endoscopically resected samples of 62 serrated polyps [20 hyperplastic polyps (HPs), 16 traditional serrated adenomas (TSAs) and 26 sessile serrated adenoma-polyps (SSA/Ps)], as well as 20 non-serrated adenomas, 20 carcinoma in adenomas (CIAs) and 18 early pure colorectal carcinomas without any adenoma component (EPCs). Based on immunostaining score, high DCLK1 expression was detected in 20.0% of HPs (23.1% of microvesicular HPs and 14.3% of goblet cell HPs), 37.5% of TSAs, 7.7% of SSA/Ps, 80.0% of non-serrated adenomas, 75.0% of CIAs and 50.0% of EPCs. Negative or low DCLK1 expression was frequently observed in TSAs (P<0.005), SSA/Ps (P<0.00001) and EPCs (P<0.04) compared with non-serrated adenomas and CIAs. In addition, negative or low DCLK1 expression was significantly more frequent in SSA/Ps (92.3%) compared with TSAs (62.5%; P<0.05). Thus, the expression pattern of DCLK1 between the serrated pathway and ACS differed, indicating that DCLK1 expression may perform a secondary role in serrated tumorigenesis. In addition, the data indicates that EPCs may contain tumors derived from the serrated pathway as well as the ACS.

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“…Furthermore, previous studies have demonstrated DCLK1 expression in multiple types of solid tumor, including colon, intestinal and pancreatic cancer, and HCC (20,(25)(26)(27). In addition, it has been revealed that patients with a high (>4) DCLK1 staining score are associated with increased cancer-specific mortality rates compared with those with a low (0-4) DCLK1 staining score in colorectal neoplasia (27). To the best of our knowledge, no study has been performed to assess the association between DCLK1 expression and survival outcome in patients with HCC.…”

Section: Introductionmentioning

confidence: 99%

Expression and prognostic significance of doublecortin‑like kinase 1 in patients with hepatocellular carcinoma

2017

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Abstract. Doublecortin-like kinase 1 (DCLK1), a putative cancer stem cell marker in intestinal and pancreatic tumors, is associated with tumor pathogenesis and progression, and poor survival outcomes in numerous types of cancer. However, DCLK1 expression and its prognostic value remain unclear in hepatocellular carcinoma (HCC). In the present study, the expression of DCLK1 was assessed using immunohistochemistry in 96 resected HCC and 68 adjacent tissue specimens. The staining intensity and the percentage of stained cells were scored on a scale of 0-3 and 0-4, respectively. Tissue was defined as positive for DCLK1 if the composite multiple score was >3. Cytoplasmic expression of DCLK1 was observed in HCC and adjacent tissue specimens with an expression rate of 81% (78/96) and 74% (50/68), respectively; the median score was 4.6 and 3.9, respectively, and no statistically significant difference was observed between HCC and adjacent tissues (P=0.087). DCLK1 expression was positively associated with intrahepatic metastasis (P=0.035). Furthermore, univariate analysis revealed that DCLK1 expression was significantly associated with poor disease-free survival (DFS) and overall survival (P=0.024 and 0.034). Multivariate analysis also demonstrated that DCLK1 expression was an independent prognostic factor for DFS in HCC (P=0.019; hazard ratio, 1.546; 95% confidence interval, 1.330-1.725). Stratified Kaplan-Meier survival curves revealed that DCLK1 expression predicted poorer DFS with respect to positivity for three characteristics: Portal venous metastasis, intrahepatic metastasis, and cirrhosis (P=0.020, P=0.007 and P=0.017, respectively). Collectively, the results of the present study suggested that DCLK1, functioning as a tumor promoter, is frequently overexpressed in HCC, and that DCLK1 expression is associated with poor DFS in patients with HCC. DCLK1 may represent a promising therapeutic target in HCC and requires further study.

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DCLK1 immunoreactivity in colorectal neoplasia

Cited by 57 publications

References 23 publications

Functional implication of Dclk1 and Dclk1-expressing cells in cancer

Functional implication of Dclk1 and Dclk1-expressing cells in cancer

Expression of doublecortin and CaM kinase‑like‑1 protein in serrated neoplasia of the colorectum

Expression and prognostic significance of doublecortin‑like kinase 1 in patients with hepatocellular carcinoma

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