Search

Aims: Our study focused on exploring the feasible prognostic laboratory parameters of HCC and establishing a score model to estimate individualized overall survival (OS) in HCC after resection. Methods: Four hundred and sixty‐one patients with HCC who underwent hepatectomy between January 2010 and December 2017 was enrolled in this investigation. Cox proportional hazards model was conducted to analyze the prognostic value of laboratory parameters. The score model construction was based on the forest plot results. Overall survival was evaluated by Kaplan‐Meier method and the log‐rank test. The novel score model was validated in an external validation cohort from a different medical institution. Results: We identified that alpha fetoprotein (AFP), total bilirubin (TB), fibrinogen (FIB), albumin (ALB), and lymphocyte (LY) were independent prognostic factors. High AFP, TB, FIB (HR > 1, p < 0.05), and low ALB, LY (HR < 1, p < 0.05) were associated with the survival of HCC. The novel score model of OS based on these five independent prognostic factors achieved high C‐index of 0.773 (95% confidence interval [CI]: 0.738–0.808), which was significantly higher than those of the single five independent factors (0.572–0.738). The score model was validated in the external cohort whose C‐index was 0.7268 (95% CI: 0.6744–0.7792). Conclusion: The novel score model we established was an easy‐to‐use tool which could enable individualized estimation of OS in patients with HCC who underwent curative hepatectomy. [ABSTRACT FROM AUTHOR]

Background: Identifying therapeutic targets and prognostic biomarkers significantly contributes to individualized treatment of acute myeloid leukemia (AML). Dihydropyrimidinase‐like 2 (DPYSL2) expression was decreased in homoharringtonine (HHT)‐resistant AML cells, which were established by our group. DPYSL2 plays an important role in axon growth and has oncogene effect in glioblastoma. However, little research has been conducted to investigate the function of DPYSL2 in AML pathogenesis. Methods: Auto‐docking was used to reveal the targeting relationship between HHT and DPYSL2. Overall survival (OS), event‐free survival (EFS), and relapse‐free survival (RFS) were used to evaluate the prognostic impact of DPYSL2 for AML. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. In vivo growth and survival were assessed using a xenotransplantation mice model. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML and were confirmed by Western blot. Results: We found DPYSL2 was the target of HHT. Next, we found AML cell lines and patients had higher DPYSL2 expression levels than the normal samples. Further multivariate analysis demonstrated that high DPYSL2 expression was an independent poor prognostic factor for OS, EFS, and RFS in AML. Inhibition of DPYSL2 expression suppressed cell growth, induced apoptosis in AML cell lines, and prolonged the survival of AML xenograft NCG mice. Through RNA‐seq analysis from TCGA and our data, the JAK2/STAT3/STAT5‐PI3K P85/AKT/GSK3b axis was thought to be the critical pathway in regulating DPYSL2 in AML development. Conclusions: We first time confirmed that DPYSL2 was a target of HHT and played an oncogene role in AML by regulating JAK/STAT signaling pathway. Therefore, DPYSL2 could serve as a novel prognostic marker and therapeutic target for AML treatment. [ABSTRACT FROM AUTHOR]