Serum Midkine as a Prognostic Biomarker for Patients With Hepatocellular Carcinoma

Abstract

Gene expression profiles of paired hepatocellular carcinoma (HCC) and adjacent noncancerous liver tissue samples revealed preferential expression of midkine in HCC. This finding suggested the clinical usefulness of midkine measurement in serum for monitoring HCC treatment response, recurrence, and progression. A prospective study in 285 patients, 144 in complete remission and 141 at risk for developing de novo HCC, was conducted. The changes in serum midkine level were in parallel with disease activity in about 81% of patients with HCC. The study also revealed that rapidly rising serum midkine levels occurred in patients in the terminal stage of HCC. The rising rate of serum midkine levels was inversely correlated with remaining survival days. However, serum midkine measurement did not detect emergence of new HCC in most patients in complete remission and in high-risk people without a history of HCC. Serum midkine levels can be useful to monitor HCC progression, and a sharp rise signals the approach of end of life in patients with HCC.

Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

“…The YAP1-TEAD complex activates numerous growth-related genes in HCC [27]. Accordingly, we found a significant positive correlation of YAP1 and YAP1-TEAD levels with the expression of the proliferation marker Ki67, and the progression markers CTGF [28, 29] and MDK [19, 20], in HCC.…”

“…No significant differences between the two groups occurred as concerns patients' sex, etiology, presence of cirrhotic liver, and Edmondson-Steiner grade. Significantly higher tumor size, alpha-fetoprotein secretion, proliferation index (Ki67 expression), YAP1 expression, and Midkine expression (as index of poor differentiation), [19, 20], were found in HCCP than in HCCB.…”

Circulating midkine in malignant and non-malignant colorectal diseases

“…Not only circulating cytokine levels did not correspond well with histological T stage but there was only a weak tendency towards positive correlation with tumor size. However, since midkine is a heparin-binding cytokine, it may result from the phenomenon of midkine sequestering by endothelial heteroglycans that may buffer an early rise in its levels in the circulation [25]. Midkine was especially increased in patients with secondary tumors located in distant organs (mainly liver) while its association with lymph node metastasis was of borderline significance.…”

Midkine and syndecan-1 levels correlate with the progression of malignant gastric cardiac adenocarcinoma

“…MK promotes carcinogenesis by enhancing fibrinolysis, cell transformation, migration, cell survival and anti-apoptotic activity through a molecular mechanism that remains to be elucidated (22). The overexpression of MK is common in numerous malignant tumor types and particularly in advanced cancer types, including esophageal (23), gastric (1,24), colorectal (25), liver (26), pancreatic, lung (27) and breast (28) cancer and neuroblastoma (29). The overexpression of MK is closely correlated with tumor development and progression (30); however, expression levels of MK in GCA have yet to be reported.…”