A Large-Scale Multicenter Study Validates Aldo-Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma.

Aldo-keto reductase family 1 member B10 (AKR1B10) is a secretory protein overexpressed in hepatocellular carcinoma (HCC). We aimed to evaluate AKR1B10 as a serum marker for detection of HCC. Herein, we conducted a cohort study that consecutively enrolled 1,244 participants from three independent hospitals, including HCC, healthy controls (HCs), benign liver tumors (BLTs), chronic hepatitis B (CHB), and liver cirrhosis (LC). Serum AKR1B10 was tested by time-resolved fluorescent assays. Data were plotted for receiver operating characteristic (ROC) curve analyses. Alpha-fetoprotein (AFP) was analyzed for comparison. An exploratory discovery cohort demonstrated that serum AKR1B10 increased in patients with HCC (1,567.3 ± 292.6 pg/mL; n = 69) compared with HCs (85.7 ± 10.9 pg/mL; n = 66; P < 0.0001). A training cohort of 519 participants yielded an optimal diagnostic cutoff of serum AKR1B10 at 267.9 pg/mL. When ROC curve was plotted for HCC versus all controls (HC + BLT + CHB + LC), serum AKR1B10 had diagnostic parameters of the area under the curve (AUC) 0.896, sensitivity 72.7%, and specificity 95.7%, which were better than AFP with AUC 0.816, sensitivity 65.1%, and specificity 88.9%. Impressively, AKR1B10 showed promising diagnostic potential in early-stage HCC and AFP-negative HCC. Combination of AKR1B10 with AFP increased diagnostic accuracy for HCC compared with AKR1B10 or AFP alone. A validation cohort of 522 participants confirmed these findings. An independent cohort of 68 patients with HCC who were followed up showed that serum AKR1B10 dramatically decreased 1 day after operation and was nearly back to normal 3 days after operation. Conclusion: AKR1B10 is a potent serum marker for detection of HCC and early-stage HCC, with better diagnostic performance than AFP.

Serum AKR1B10 predicts the risk of hepatocellular carcinoma - A retrospective single-center study.

OBJECTIVES: AKR1B10, first cloned from liver cancer tissues, has recently been reported to be up-regulated significantly in hepatocellular carcinoma (HCC) tissues, but the relationship between serum level of AKR1B10 and the risk of HCC is not understood. METHODS: 170 HCC patients and 120 health donors from October 2014 to March 2017 were recruited in the affiliated hospital of Guilin Medical University. Serum AKR1B10 in all cases were detected and in 30 HCC patients were analyzed preoperatively and postoperatively by Time-resolved fluoroimmunoassay. RESULTS: The level of serum AKR1B10 was significantly higher in HCC patients (1800.24±2793.79) than in health donors (129.34±194.129), and downregulation of serum AKR1B10 in HCC patients was observed after hepatectomy. When samples were grouped according to the serum level of AKR1B10 (≥232.7pg/ml), serum AKR1B10 positively correlated to serum AFP (χ2=6.295, P=0.012), ALT (χ2=18.803, P=0.000), AST (χ2=33.421, P=0.000), tumor nodule number (χ2=6.777, P=0.009), cirrhosis (χ2=43.458, P=0.000), and tumor size (χ2=6.042, P=0.014) in the Chi-square test. CONCLUSIONS: Diagnosis of HCC could be improved using the both predictors of serum AKR1B10 and AFP. AKR1B10 was thus considered to be a new serological biomarker for HCC.

Serum sphingosine 1-phosphate in hepatocellular carcinoma patients is related to HBV infection.

PURPOSE: Serum predictors for early diagnosis of hepatocellular carcinoma (HCC) have been investigated. Sphingosine-1-phosphate (S1P) has been widely reported to promote the survival of many types of cancer cells. However, the potential of serum S1P as a diagnostic marker in HCC has not been well characterized. The aim of this study was to identify the relationship between serum S1P and the risk of HCC. METHODS: We retrospectively reviewed serum S1P in 63 HCC patients and 39 normal people. Receiver operating characteristic (ROC) curve analysis was performed to define the cut-off value of S1P in the serum. Chi-square test, t-test and multivariate regression analysis were used to investigate the association between serum S1P and individual clinicopathologic parameters. RESULTS: S1P showed significantly higher level in healthy subjects (1.372±0.116 µM) than that in patients (1.372±0.116 µM). Serum S1P in HCC patients was positively correlated to globulin (t = -3.122, p=0.003), hepatitis B virus (HBV) DNA copies (x2=4.386, p=0.036) and negatively related to AST (x2=2.870, p=0.09). Besides, part of the amount of serum S1P was negatively correlated to albumin (correlation coefficient (ß) = -0.056) and positively correlated to alanine aminotransferase (ALT) (ß=0.016) according to the regression analysis. CONCLUSIONS: These results suggested that serum S1P could be used as an auxiliary marker for HCC diagnosis, and used to monitor HBV infection in patients with HCC.

Serum sphingosine negatively correlates with albumin predicting the risk of hepatocellular carcinoma.

BACKGROUND: The roles of sphingosine in various cancers have not been fully investigated. Our aim was to identify the relationship between serum sphingosine and the risk of hepatocellular carcinoma (HCC). METHODS: Serum sphingosine in 34 normal people and 73 HCC patients were reviewed retrospectively. Receiver operating characteristic curve analysis was performed to determine the cut-off values of sphingosine in the serum. Chi-square test, t test and regression analysis were used to test the association between serum sphingosine and individual clinicopathologic parameters. RESULTS: Serum sphingosine was higher in HCC patients (155.91±331.5 ng/mL) with normal persons as the control (30.92±29.4 ng/mL). The sphingosine threshold according to ROC curve was set at 22.5 ng/mL with a sensitivity of 74%, and a specificity of 55.9%. Meanwhile, sphingosine in HCC patients with abnormal albumin was significantly higher than that in patients with normal albumin (t=2.452, P=0.019). When HCC patients were divided into two groups serum sphingosine was negatively associated with albumin in HCC patients (χ2=4.469, P=0.035). Moreover, the logistic regression analysis showed that large tumor size (P=0.018, OR=0.13) and a low albumin (P=0.005, OR=8.856) were two independent risk factors for serum sphingosine upregulation. High AFP coupled with high serum sphingosine, high sphingosine and high AFP respectively were found in 91.2%, 75.4%, 73% of the HCC patients. CONCLUSIONS: These results suggest that serum sphingosine could be treated as a marker for the risk of HCC. AFP and sphingosine in the serum could be used together for HCC diagnosis.

[Impact of platelet count on prognosis of stage II-III colorectal cancer receiving adjuvant chemotherapy].

OBJECTIVE: To analyze the impact of platelet count on the prognosis of stage II-III colorectal cancer receiving adjuvant chemotherapy. METHODS: Clinical and follow-up data of 286 patients with stage II-III colorectal cancer receiving adjuvant FOLFOX chemotherapy from March 2003 to October 2011 were analyzed retrospectively. Associations of baseline blood platelet count before chemotherapy and nadir blood platelet count during chemotherapy with relapse and death after adjuvant chemotherapy were analyzed by ROC curve and the optimal cutoff was selected. The association of the blood platelet count and the prognosis was analyzed by Kaplan-Meier and Cox regression model. RESULTS: ROC curve showed the baseline blood platelet count was associated with recurrence (AUC=0.588, P=0.034). The optimal cutoff affecting recurrence was 276×10(9)/L. Kaplan-Meier showed those with baseline platelet count >276×10(9)/L receiving adjuvant chemotherapy had worse disease free survival (DFS) than those with baseline platelet count ≤276×10(9)/L, whose 5-year disease free survival(DFS) was 66% and 80% respectively (P=0.013). Cox regression analysis revealed baseline platelet count >276×10(9)/L was an independent unfavorable factor for DFS of adjuvant chemotherapy in colorectal cancer (HR=1.865, 95% CI: 1.108-3.141, P=0.019). CONCLUSION: Colorectal cancer patients receiving adjuvant chemotherapy with baseline platelet count >276×10(9)/L have worse prognosis.