Hepatocellular carcinoma (HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called “liquid biopsy” is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma.

This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small- and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (P < 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCa patients (P = 0.0424; hazard ratio, 2.95). miR-107 overexpression in PCa cells induced G1/S arrest with the production of p21 and inhibited cell proliferation through the transcriptional regulation of Notch2. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. Depletion of the tumor suppressor miR-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCa.

Abstract. Background: PDZ-binding kinase/T-celloriginated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer. PBK/TOPK is associated with tumor cell development and 58). Knockdown of PBK/TOPK using specific siRNAs inhibited the cell proliferation, invasion/migration of PBK/TOPK-overexpressing ESCC cell lines. Conclusion: These findings suggest that PBK/TOPK plays a crucial role in tumor malignant potential through its overexpression in ESCC.Esophageal cancer is the eighth most common cancer in the world (1) and esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal carcinomas diagnosed in Asian countries. Although surgical techniques and perioperative management have progressed, ESCC remains one of the most aggressive carcinomas of the gastrointestinal tract. Since finding molecular targets for ESCC treatment might help improve the survival of patients with this lethal disease, studies have attempted to identify biological factors involved in the malignant potential of ESCC. However, few genes have been demonstrated to be associated with biological or pathological features of ESCC, suggesting that novel genes associated with the progression of ESCC need to be identified.Because identifying molecular targets for ESCC treatment may contribute to the improvement of survival of patients with this lethal disease, several recent studies have clarified that certain molecules, such as cyclo-oxygenase 2 (COX2), B-cell lymphoma (BCL2), tumor protein P53 (TP53), p16, cyclin D1, FAS, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and E-cadherin (2-6), have important roles in tumorigenesis and the development of ESCC. Moreover, various genetic and epigenetic alterations that contribute to the carcinogenesis of ESCC have been elucidated. In clinical settings, however, only a few molecules have been validated as diagnostic, therapeutic, or prognostic biomarkers for ESCC. These findings prompted us to further search for novel cancerassociated molecules.PDZ binding kinase/T-LAK cell originated protein kinase (PBK/TOPK) encodes a serine/threonine protein kinase and is 6457

BackgroundSeveral studies have identified the decreased expression of the tumor suppressor miR-101 in various cancers. In this study, we tested miR-101 as a potential therapeutic target and novel plasma biomarker for gastric cancer (GC).ResultsThe miR-101 expression level was significantly lower in GC tissues (P = 0.0038) and GC cell lines (P = 0.0238) than in normal gastric mucosa. Both exosomal and plasma miR-101 were significantly downregulated in GC patients compared with healthy volunteers (P = 0.0281 and P < 0.0001, respectively). Low miR-101 plasma level was significantly associated with advanced T factor, advanced disease stage, and peritoneal metastasis and predicted poor prognosis in GC patients (P = 0.0368; hazard ratio, 3.079; 95% confidence interval: 1.06–11.08). Overexpression of miR-101 in GC cells induced apoptosis by inhibiting MCL1 and suppressed cell migration and invasion by regulating ZEB1.ConclusionsDepletion of the tumor suppressor miRNA-101 in plasma is related to tumor progression and poor outcomes. Low plasma miR-101 may be a biomarker for GC, and its restoration might be a novel anticancer treatment strategy.

BackgroundAlthough adjuvant chemotherapy with S-1 after curative gastrectomy has been performed as a standard treatment for Stage II and III gastric cancer (GC) in Japan, patients with Stage III GC still have a high incidence of recurrence and a poor prognostic outcome. The aim of this study was to investigate risk factors for recurrence in patients with Stage III GC despite of curative gastrectomy followed by adjuvant chemotherapy, suggesting an indicator for more intensive management.MethodsA total of 97 patients with pathological Stage III GC underwent adjuvant chemotherapy after curative gastrectomy between 2001 and 2014, were enrolled in this study. We retrospectively analyzed their hospital records from our hospital.ResultsThe 5-year relapse-free survival (RFS) rates of patients with pStage III GC were 42.0%. Univariate and multivariate analyses for RFS revealed that venous invasion (v+) was an independent factor predicting a shorter RFS (v + vs. v-, 36.5% vs. 47.4%, P = 0.034, HR 1.82, 95% CI: 1.01–3.37). Venous invasion also predicted a shorter overall survival (OS) (v + vs. v-, 33.7% vs. 50.4%, P = 0.027). Regarding the patterns of recurrence, hematogenous recurrence was significantly occurred in patients with v + GC than those without (P = 0.022).ConclusionsStage III GC with venous invasion is a high-risk subgroup for hematogenous recurrence after curative surgery followed by adjuvant chemotherapy. More intensive and effective adjuvant chemo and/or molecular targeted therapy for Stage III GC patients with venous invasion should be considered to improve their outcomes.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4052-z) contains supplementary material, which is available to authorized users.