Abstract
Studies have reported dysregulation of TIPRL, LC3 and CD133 in liver cancer tissues. However, their respective relationships to liver cancer and roles as biomarkers for prognosis and diagnosis of liver cancer have never been studied. Here we report that the level of TIPRL is significantly correlated with levels of LC3 (Spearman r = 0.9) and CD133 (r = 0.7) in liver cancer tissues. We observed significant upregulations of TIPRL, LC3 and CD133 in hepatocellular carcinomas (HCCs) compared with adjacent normal tissues. Importantly, TIPRL, tested among additional variables, showed a significant impact on the prognosis of HCC patients. TIPRL knockdown significantly reduced expressions of LC3, CD133, stemness-related genes, as well as viability and stemness of liver cancer cell-lines, which were promoted by ectopic TIPRL expression. Either alone or as a combination, TIPRL, LC3 and CD133 showed significant values of area under the curve (AUC) and sensitivity/specificity in early liver cancer tissues. Furthermore, the statistical association and the diagnostic efficacies of TIPRL, LC3 and CD133 in HCC tissues were confirmed in a different IHC cohort. This data demonstrates that the complex involvement of TIPRL/LC3/CD133 in liver cancer aggressiveness can together or individually serve as potential biomarkers for the early detection of liver cancer.
Highlights
As the second leading cause of death worldwide, cancer causes about 1 in 6 deaths
TIPRL interacts with protein phosphatase type2Ac (PP2Ac), thereby inhibiting its activity to oppose ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) dependent phosphorylation events; while not interacting with α4, which is the mammalian homolog of Tap[42], unlike the yeast TIP413
We report the interrelationships between TIPRL, light chain 3 (LC3) and CD133 in hepatocellular carcinomas (HCCs)/liver cancer tissues are associated with cancer aggressiveness via possibly induction of cancer cell stemness, thereby providing novel biomarkers for early prognosis and diagnosis of liver cancer
Summary
As the second leading cause of death worldwide, cancer causes about 1 in 6 deaths. There were an estimated 782,000 reports of liver cancer related deaths in 2018, according to the World Health Organization (WHO)[1]. Despite rapid advances in liver cancer diagnosis and therapy in recent decades, liver cancer death rates have increased 3% per year since 2000 Public health agencies, such as WHO, have reported that this increase is mainly caused by late-stage presentation and inaccessible diagnosis and treatment: contrary to 90% of high-income countries, only 26% of low-income countries have general pathology services in the public sector[2]. Our team reported the TIPRL protein contributing to TNF-related apoptosis inducing ligand (TRAIL) resistance of liver cancers[4]. We report the interrelationships between TIPRL, LC3 and CD133 in HCC/liver cancer tissues are associated with cancer aggressiveness via possibly induction of cancer cell stemness, thereby providing novel biomarkers for early prognosis and diagnosis of liver cancer
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