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.
Highlights
Centrosomal abnormalities are among the most important features of cancer cells because centrosomes are crucial for cell cycle progression and maintenance of genome stability[1,2]
We examined the prognostic significance of SAC3D1 in hepatocellular carcinoma (HCC) using three cohorts (The Cancer Genome Atlas (TCGA)[23,24], the International Cancer Genome Consortium (ICGC)[25], and the NCBI Gene Expression Omnibus (GEO) Series (GSE10186)[26,27]
To evaluate the prognostic significance of SAC3D1 using public data-bases, we examined the information of 647 patients from 3 independent cohorts (GSE10186, n = 80; TCGA, n = 330 and ICGC, n = 237)
Summary
Centrosomal abnormalities are among the most important features of cancer cells because centrosomes are crucial for cell cycle progression and maintenance of genome stability[1,2]. A previous study suggested its role during cell cycle, centrosome duplication and spindle formation[12,13]. Tyrosine kinase inhibitors with anti-angiogenic properties have only shown modest effects in treating HCC18 Several reasons such as comorbid cirrhosis and heterogeneous histological features and clinical factors have been suggested to explain poor results. Survival benefits were observed in the patients with baseline serum AFP levels ≥400 ng/mL Another example shows that everolimus, an allosteric mTORC1 inhibitor, was unsuccessful in 546 patients during its phase III clinical trial[21], and subsequent studies indicated that the loss of tuberous www.nature.com/scientificreports/. Minimum 1st quarter Median 3rd quarter Maximum sclerosis complex[2] (TSC2) was a strong predictor for HCC sensitivity to everolimus[22] These analyses suggest that biomarker are crucial for the development of new drugs in treating HCC. The statistical analysis suggested it to be an important prognostic marker in HCC
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