Abstract
BackgroundsDevelopmental pluripotency-associated 4 (Dppa4) gene plays an important role in self-renewal and pluripotency sustainability in embryonic stem cells. It is re-expressed in several malignant tumors and is identified as a new pluripotency-related oncogene. The present study investigates the expression and clinical significance of Dppa4 in colon cancer.MethodsReal-time polymerase chain reaction and Western blotting were used to evaluate Dppa4 mRNA and protein expression in 39 pairs of fresh-frozzen colon cancer samples, which were compared with adjacent normal mucosa. The Dppa4 protein was evaluated by immunohistochemical techniques using colon tissue microarrays (TMA). The sample included 185 cancer specimens and corresponding normal colorectal mucosa. The effect of Dppa4 knockdown on colorectal cancer cell proliferation was investigated using Cell Counting Kit-8 (CCK8) assays and colony-formation assays.ResultsBoth the mRNA and protein level expression of Dppa4 gene was found to be upregulated in colon cancer tissues. Furthermore, the upregulated expression of Dppa4 was significantly correlated with the results of American Joint Committee on Cancer (AJCC) stage (P = 0.01), invasion depth (P = 0.028), nodal involvement (P = 0.012), distant metastasis (P = 0.003), and differentiation (P = 0.002). Dppa4 was also shown to be an independent prognostic indicator of disease-free survival (HR 6.118, 95 % CI 3.004–12.462) and overall survival (HR 6.348, 95 % CI 2.875–14.014) for patients with colon cancer. Knockdown of Dppa4 expression inhibited the proliferation of colorectal cancer cell lines through G1/S transition regulation.ConclusionThe results indicate that Dppa4 might play an important role in colon cancer progression and function as a novel prognostic indicator and a potential therapeutic target.
Highlights
IntroductionRecent research supports the idea that human cancers can be considered as a stem cell disease [2]
The relationship between cancer and stem cells is very astonishing [1]
Our results showed for the first time that (1) over-expression of Developmental pluripotency-associated 4 (Dppa4) was significantly associated with unfavorable clinicopathological variables and Dppa4 might be used as a novel prognostic marker for colorectal cancer
Summary
Recent research supports the idea that human cancers can be considered as a stem cell disease [2]. Developmental pluripotency-associated 4 (Dppa4) is one of the uncharacterized genes that is highly expressed in embryonic stem (ES) cells. Zhang et al Journal of Experimental & Clinical Cancer Research (2015) 34:60 the expression of Dppa might be regulated by Oct and Sox genes [11] and Dppa could modulate chromatin structure in association with DNA and histone H3 in ES cells [12]. In a study of expression of stem cell-specific marker genes in multiple malignant tumors, Dppa was found to be significantly expressed in cancer cell lines and cancer tissues, including colon cancer and colorectal cell lines [9]. The clinicopathological significance of Dppa, and its possible mechanism in colon cancer tumorigenesis and progression is still unclear
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