The clinical and prognostic significance of midkine in breast cancer patients

Abstract

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.

Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression

“…We demonstrated that ectopic overexpression of midkine remarkably remedied inhibition of Huh7 cell proliferation, migration, and invasion caused by IGF-1R suppression, suggesting that the reduced midkine expression may contribute, at least in part, to significantly reduced HCC proliferation, migration, and invasion capability induced by IGF-1R suppression. It has been shown that midkine overexpression is observed in a variety of human cancers such as gastrointestinal cancer [17], colorectal cancer [38], lung cancer [39], breast cancer [40], pancreatic cancer [41], and HCC [42,43]. Concordant with our findings, Rawnaq et al indicated that the expression of midkine promoted the proliferation and migration in pancreatic cancer cells, and siRNA-mediated knockdown of midkine was associated with decreased proliferation and migration in pancreatic cancer cells [41].…”

Identification of Biomarkers for Breast Cancer Using Databases

“…The oncogenic isoform of HER2, HER2Δ16, is expressed with HER2 in nearly 50% of HER2 positive breast tumors, and HER2Δ16 drives metastasis and resistance to drugs including tamoxifen and trastuzumab 32. Other molecules such as thyroid hormone receptor-interacting protein 13, DLDN11 , CD44, and midkine protein in breast cancer may be potential prognostic biomarkers and therapeutic targets 33–36…”

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

“…One study found breast cancer patients to have higher plasma levels of midkine than their healthy controls [ 38 ]. Another study also found a correlation between MK protein expression and malignant status and prognosis of breast cancer patients [ 39 ]. Zhu et al found serum MK levels to be clearly increased in hepatocellular cancer patients and suggested they could be used to diagnose hepatocellular cancer with a high sensitivity.…”