SAC3D1: a novel prognostic marker in hepatocellular carcinoma

Abstract

Centrosome-associated proteins are recognized as prognostic factors in many cancers because centrosomes are critical structures for the cell cycle progression and genomic stability. SAC3D1, however, is associated with centrosome abnormality, although its prognostic potential has not been evaluated in hepatocellular carcinoma (HCC). In this study, 3 independent cohorts (GSE10186, n = 80; TCGA, n = 330 and ICGC, n = 237) were used to assess SAC3D1 as a biomarker, which demonstrated SAC3D1 overexpression in HCC tissues when compared to the matched normal tissues. Kaplan-Meier survival analysis also showed that its overexpression was associated with poor prognosis of HCC with good discriminative ability in 3 independent cohorts (GSE10186, P = 0.00469; TCGA, P = 0.0000413 and ICGC, P = 0.0000114). Analysis of the C-indices and AUC values further supported its discriminative ability. Finally, multivariate analysis confirmed its prognostic significance (GSE10186, P = 0.00695; TCGA, P = 0.0000289 and ICGC, P = 0.0000651). These results suggest a potential of SAC3D1 as a biomarker for HCC.

Figure 1

Comparison of SAC3D1 gene expression between cancer and matched normal liver tissues in the ICGC cohort. (A) The SAC3D1 expression levels in HCC and matched normal liver tissues. (B) The difference in SAC3D1 expression values between HCC and matched normal liver tissues. The scatters on the graph are values obtained by subtracting normal SAC3D1 expression from cancer SAC3D1 expression.

Figure 2

Kaplan-Meier survival analysis of HCC patients with respect to SAC3D1 gene expression. Overall survival in the GSE10186 (A–D), TCGA (E–H,J,K), and ICGC (I) cohorts were examined with respect to SAC3D1 gene expression. Survival analysis was performed for all the patients in each cohort (A,E,I) or for each subgroup of patients in each cohort. P-value was calculated using the log-rank test and is provided at the bottom right of each graph.

Figure 3

Time-dependent area under the curve (AUC) analysis and receiver operating characteristic (ROC) curves at 5 years with respect to SAC3D1 gene expression in the GSE10186, TCGA, and ICGC cohorts. Time-dependent AUC analysis and ROC curves at 5 years in the GSE10186 (A,B), TCGA (C,D), and ICGC (E) cohorts with respect to SAC3D1 gene expression (red: all patients, green: alcohol consuming patients, blue: Hepatitis B patients, and light blue: Hepatitis C patients). C-index values are shown at the bottom right of graphs (A and C). AUC values at 5 years are shown at the bottom right of graphs (B and D).