Promoter mutations in telomerase reverse transcriptase (TERT) and telomere length have been studied in various tumors. In the present study, the frequency and clinical characteristics of TERT promoter mutation and telomere length were studied in hepatocellular carcinoma (HCC). TERT promoter mutation and telomere length were analyzed in 162 tumor samples of the patients with HCC by sequencing and real-time PCR, respectively. The TERT promoter mutation rate was 28.8% (46/160) in HCC and was associated with males (P = 0.027). The telomere length was not significantly different in the presence of a TERT promoter mutation but was shorter in high-grade tumor stages (P = 0.048). Survival analyses showed that poor overall survival was associated with longer telomere length (P = 0.013). However, the TERT promoter mutation did not have a prognostic value for HCC. Multivariate survival analyses demonstrated that the telomere length was an independent prognostic marker for poor overall survival (hazard ratio = 1.75, 95% confidence interval: 1.046–2.913, P = 0.033). These data demonstrated that TERT promoter mutation is a frequent event in HCC; however, telomere length, but not the presence of a TERT promoter mutation, might have potential value as a prognostic indicator of HCC.

Purpose This paper aims to examine how the relationship between abnormal audit fees and audit quality changed after adoption of the International Financial Reporting Standards (IFRS) in Korea. Design/methodology/approach Using empirical data collected over the period from 2008 to 2013, this study analyzes the association between abnormally high/low audit fee and audit quality. This study uses linear regression to test the hypothetical relation using discretionary accrual as a proxy for audit quality. Findings This study finds that there exists no significant relationship between abnormally high audit fees and audit quality measured by the magnitude of discretionary accruals in the pre-IFRS adoption period. However, the relationship between abnormally high audit fees and the magnitude of discretionary accruals turns to be positive in the post-IFRS adoption period. These finding suggests that the IFRS enables some clients to engage more discretion in the choice of discretionary accruals and auditors charge higher audit fees in return for allowing the discretion for such clients. Practical implications This study provides insight to regulators of the need to review carefully the financial statements of firms with abnormally high audit fees, and to investors to be more cautious when using financial information about these firms. Originality/value To the best of authors’ knowledge, this is the first study to assess IFRS impact on audit fee-quality relation. Also, unique Korean audit market with intensifying competition and discounting audit fee provides interesting setting to review the impact of abnormal audit fee on audit quality.

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Abstract. Mutations in the promoter region of telomerase reverse transcriptase (TERT) and alterations in telomere length (TL) have been the focus of research in various types of cancer. In the present study, the frequency and clinical characteristics of TERT promoter mutations and TL were studied in non-small cell lung cancers (NSCLC). TERT promoter mutations and TL were analyzed in 188 patients using DNA sequencing and the reverse transcription-quantitative polymerase chain reaction, respectively. The TERT promoter mutation rate was observed to be 2.2% (4/188 NSCLC cases), and it was significantly associated with regional lymph node invasion (P<0.001). No significant difference in TL was observed between the patients with and without TERT promoter mutations. TL was decreased in males (P=0.058 vs. females) and smokers (P=0.008 vs. non-smokers). Survival analyses demonstrated poor prognoses for patients with NSCLC with TERT promoter mutations (P<0.001). Multivariate survival analyses demonstrated that TERT promoter mutations were an independent prognostic marker for poor overall survival (P=0.045). The results of the present study demonstrated that TERT promoter mutation was not frequent in NSCLC; however, it may have value as a prognostic marker in NSCLC.

Big data analysis has revealed the upregulation of cell division cycle associated 8 (CDCA8) in human hepatocellular carcinoma (HCC) and its poorer survival outcome. However, the functions of CDCA8 during HCC development remain unknown. Here, we demonstrate in vitro that CDCA8 silencing inhibits HCC cell growth and long-term colony formation and migration through the accumulation of the G2/M phase cell population. Conversely, CDCA8 overexpression increases the ability to undergo long-term colony formation and migration. RNA sequencing and bioinformatic analysis revealed that CDCA8 knockdown led to the same directional regulation in 50 genes (25 down- and 25 upregulated). It was affirmed based on protein levels that CDCA8 silencing downregulates the levels of cyclin B1 and p-cdc2 and explains how it could induce G2/M arrest. The same condition increased the protein levels of tumor-suppressive ATF3 and GADD34 and inactivated AKT/β–catenin signaling, which plays an important role in cell growth and stemness, reflecting a reduction in sphere-forming capacity. Importantly, it was demonstrated that the extent of CDCA8 expression is much greater in CD133+ cancer stem cells than in CD133− cancer cells, and that CDCA8 knockdown decreases levels of CD133, p-Akt and β-catenin and increases levels of ATF3 and GADD34 in the CD133+ cancer stem cell (CSC) population. These molecular changes led to the inhibition of cell growth and sphere formation in the CD133+ cell population. Targeting CDCA8 also effectively suppressed tumor growth in a murine xenograft model, showing consistent molecular alterations in tumors injected with CDCA8siRNA. Taken together, these findings indicate that silencing CDCA8 suppresses HCC growth and stemness via restoring the ATF3 tumor suppressor and inactivating oncogenic AKT/β–catenin signaling, and that targeting CDCA8 may be the next molecular strategy for both primary HCC treatment and the prevention of metastasis or recurrence.