Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma

Ota, Kazutoshi; Fujimori, Hiroaki; Ueda, Mitsuharu; Jono, Hirofumi; Shinriki, Satoru; Ota, Tomoko; Sueyoshi, Tetsuro; Taura, Manabu; Taguma, Ayaka; Kai, Hirofumi; Shinohara, Masanori; Ando, Yukio

doi:10.3892/ijo_00000729

Cited by 7 publications

(2 citation statements)

References 34 publications

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“…qRT-PCR analysis showed that Brd4, Myc, and Tp53 mRNA expression increased with the progression from NILM to SCC, and each marker was significantly more highly expressed in SCC specimens than in NILM, LSIL, and HSIL specimens. These observations are in line with previous studies of OSCC [21,31,32]. For example, Wu et al [21] reported that the level of Brd4 mRNA was aberrantly upregulated in head and neck SCC samples and a 4NQO-induced OSCC animal model.…”

Section: Discussionsupporting

confidence: 90%

“…For example, Wu et al [21] reported that the level of Brd4 mRNA was aberrantly upregulated in head and neck SCC samples and a 4NQO-induced OSCC animal model. Several studies found that c-Myc and p53 were overexpressed in OSCC tissues and TSCCA and CAL-27 cell lines, compared with their levels in normal tissues and normal human oral keratinocytes cells [31,32].…”

Section: Discussionmentioning

confidence: 99%

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Novel Cytological Model for the Identification of Early Oral Cancer Diagnostic Markers: The Carcinoma Sequence Model

Kawaharada¹,

Yamazaki²,

Maruyama³

et al. 2021

Preprint

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Most oral squamous cell carcinomas (OSCCs) arise from oral epithelial dysplasia; however, there is no useful marker for early OSCC detection, likely owing to the inability to continuously observe the carcinoma sequence. We aimed to establish an experimental model to observe changes in the sequential expression pattern of mRNA and protein in the same rat using liquid-based cytology techniques. Cytology specimens were collected from a 4-nitroquinoline 1-oxide-induced rat tongue cancer model at 2, 5, 8, 11, 14, 17, and 21 weeks. We examined candidate biomarker expression using immunocytochemistry and quantitative real-time PCR. The percentage of positively stained nuclei was calculated as the labeling index (LI). All rats had OSCC of the tongue at 21 weeks. Brd4 (Brd4), Myc (c-Myc), and Tp53 (p53) mRNA levels were upregulated during progression from negative for intraepithelial lesion or malignancy to SCC. Brd4- and c-Myc-LI were increased in low- and high-grade squamous intraepithelial lesions and SCC specimens. p53-LI was significantly increased in SCC specimens. Our experimental model allowed the observation of sequential morphological changes and mRNA and protein expression patterns in the same rat during carcinogenesis. By reducing the false negative rate, BRD4 and c-Myc can be useful markers for the early detection of OSCC.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Novel Cytological Model for the Identification of Early Oral Cancer Diagnostic Markers: The Carcinoma Sequence Model

Kawaharada¹,

Yamazaki²,

Maruyama³

et al. 2021

Preprint

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The clinical and prognostic significance of midkine in breast cancer patients

Tian

Zhang

et al. 2015

Tumor Biol.

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Midkine overexpression has been shown to be a tumor biomarker in several types of human cancer, but little is known about the clinical significance of midkine in breast cancer patients. The aim of this study was to analyze the expression of midkine in breast cancer and its correlation with clinicopathological characteristics, including breast cancer patient's survival. The expression status of midkine in breast cancer from Gene Expression Omnibus (GEO accession number: GDS3853) was observed initially. Furthermore, the expression of midkine messenger RNA (mRNA) and protein was examined in breast cancer and normal mammary tissues through real-time PCR and immunohistochemistry. Moreover, the relationship of midkine protein expression with clinical characteristics of 170 breast cancer patients was analyzed by immunohistochemistry. In our results, midkine was up-expressed in breast cancer tissues compared with normal mammary tissues in microarray data (GDS3853). Midkine mRNA and protein expression was significantly increased in breast cancer tissues than in normal mammary tissues. By immunohistochemistry, high levels of midkine protein were positively associated with the status of clinical stage, T classification, N classification, and M classification in breast cancer patients. Furthermore, midkine overexpression was an independent poor prognostic indicator for the survival of patients with breast cancer. In conclusion, overexpression of midkine protein serves as an unfavorable prognostic biomarker in breast cancer patients.

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Positive expression of Midkine predicts early recurrence and poor prognosis of initially resectable combined hepatocellular cholangiocarcinoma

Chen

Chiu

et al. 2018

BMC Cancer

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BackgroundPost-surgical prognosis is usually poor for combined hepatocellular cholangiocarcinoma (CHCC-CC), a rare primary liver cancer. Although midkine (MK) is a prognostic biomarker for several known cancers, it is not known whether it can be used as such in resectable CHCC-CC. This study examined whether MK expression can predict recurrence and survival in patients with resectable CHCC-CC.MethodsWe retrospectively enrolled 52 patients with resectable CHCC-CC who had received curative hepatic resections. MK expression was assessed in post-surgical immunohistochemical studies of specimens in paraffin blocks. Clinical outcomes were analyzed from medical records.ResultsTwo-year disease-free and three-year overall survival rates were 42.1% and 44.6%. MK was expressed in 30 patients. Univariate analysis showed patients positively expressing MK had a significantly poorer 2-year disease free and three-year overall survival. Multivariate analysis found positive MK expression independently predicted recurrence.ConclusionsPositive expression of MK predicts poor prognosis in patients with resectable CHCC-CC.

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Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma

Cited by 7 publications

References 34 publications

Novel Cytological Model for the Identification of Early Oral Cancer Diagnostic Markers: The Carcinoma Sequence Model

Novel Cytological Model for the Identification of Early Oral Cancer Diagnostic Markers: The Carcinoma Sequence Model

The clinical and prognostic significance of midkine in breast cancer patients

Positive expression of Midkine predicts early recurrence and poor prognosis of initially resectable combined hepatocellular cholangiocarcinoma

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