A 15-gene signature for prediction of colon cancer recurrence and prognosis based on SVM
GENE
Authors: Xu, Guangru; Zhang, Minghui; Zhu, Hongxing; Xu, Jinhua
Abstract
Objective: To screen the gene signature for distinguishing patients with high risks from those with low-risks for colon cancer recurrence and predicting their prognosis. Methods: Five microarray datasets of colon cancer samples were collected from Gene Expression Omnibus database and one was obtained from The Cancer Genome Atlas (TCGA). After preprocessing, data in GSE17537 were analyzed using the Linear Models for Microarray data (LIMMA) method to identify the differentially expressed genes (DEGs). The DEGs further underwent PPI network-based neighborhood scoring and support vector machine (SVM) analyses to screen the feature genes associated with recurrence and prognosis, which were then validated by four datasets GSE38832, GSE17538, GSE28814 and TCGA using SVM and Cox regression analyses. Results: A total of 1207 genes were identified as DEGs between recurrence and no-recurrence samples, including 726 downregulated and 481 upregulated genes. Using SVM analysis and five gene expression profile data confirmation, a 15-gene signature (HESS, ZNF417, GLRA2, OR8D2, HOXA7, FABP6, MUSK, HTR6, GRIP2, KLRK1, VEGFA, AKAPI2, RHEB, NCRNA00152 and PMEPAI) were identified as a predictor of recurrence risk and prognosis for colon cancer patients. Conclusion: Our identified 15-gene signature may be useful to classify colon cancer patients with different prognosis and some genes in this signature may represent new therapeutic targets. (C) 2016 Published by Elsevier B.V.
Serum Liver-Type Fatty Acid-Binding Protein Is a Possible Prognostic Factor in Human Chronic Liver Diseases From Chronic Hepatitis to Liver Cirrhosis and Hepatocellular Carcinoma
HEPATOLOGY COMMUNICATIONS
Authors: Eguchi, Akiko; Hasegawa, Hiroshi; Iwasa, Motoh; Tamai, Yasuyuki; Ohata, Keiichi; Oikawa, Tsuyoshi; Sugaya, Takeshi; Takei, Yoshiyuki
Abstract
Liver-type fatty acid-binding protein (L-FABP) is a key regulator of fatty acid metabolism, but serum L-FABP levels are not well investigated in chronic liver diseases. We aimed to elucidate the prognostic ability of serum L-FABP in human chronic liver diseases and compare it with the albumin-bilirubin (ALBI) score. In 242 chronic liver disease patients, including chronic hepatitis (CH, n=100), liver cirrhosis (LC, n=142), and presence of hepatocellular carcinoma (HCC, n=144), serum L-FABP levels were correlated with liver function (P<0.0001), increased in LC compared with CH (P<0.01), and correlated to ALBI score (P<0.0001). Serum L-FABP levels were increased in the presence of HCC (P<0.0001), correlating to des-gamma-carboxy prothrombin (P<0.0001), alpha-fetoprotein (P=0.009), and Barcelona-Clinic Liver Cancer stage. In the average follow-up period of 1,054 days, serum L-FABP levels were elevated (P<0.0001) in patients who eventually died. The area under the curve (AUC) of serum L-FABP (0.764) was higher than that of ALB (0.709), and the patients with serum L-FABP6.8 ng/mL had significantly longer rates of survival (P<0.0001). Serum L-FABP (hazard ratio [HR] 4.0; P<0.001), HCC (HR 3.7; P=0.001), ALBI score (HR 2.7; P<0.001), and age (HR 1.0; P=0.049) were independent predictors of survival. In the subgroup who maintained liver function, the AUC of serum L-FABP (0.751) was higher than that of ALB (0.643). In this subgroup, serum L-FABP (HR 4.4; P=0.002) and HCC (HR 13.9; P<0.001) were independent predictors of survival. Conclusion: Serum L-FABP is a possible predictor of survival in chronic liver diseases from CH to LC and HCC, including any subgroup that maintains liver function.