Abstract
Unexpected high risk of synchronous/metachronous hepatocellular carcinoma (HCC) and transitional cell carcinoma (TCC) co-occurrence has been discovered previously. Here, we searched for genetic variation contributing to the co-occurrence of this double primary cancer (DPC). Using targeted exome sequencing, a panel of variants associated with concurrent DPC was identified. However, only a nonsynonymous variant within the Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1) gene was associated with DPC occurrence (p = 0.002), compared with that in the healthy population. Further independent cohort verification analysis revealed that the SYNE1-rs9479297-TT genotype (versus TC + CC genotypes) was enriched in patients with DPC, compared with that in those with TCC alone (p = 0.039), those with HCC alone (p = 0.006), those with non-HCC/non-TCC (p < 0.001), and healthy population (p < 0.001). SYNE1 mRNA expression reduced in both patients with HCC and TCC, and its lower expression in HCC was associated with shorter recurrence-free (p = 0.0314) and metastasis-free (p = 0.0479) survival. SYNE1-rs9479297 genotypes were correlated with tissue SYNE1 levels and clinical outcomes in HCC patients. Finally, SYNE1 silencing enhanced the cell proliferation and migration of HCC/TCC cells. In conclusion, SYNE1-rs9479297 genotypes were associated with HCC/TCC DPC co-occurrence and correlated with SYNE1 expression, which in turn contributed to HCC/TCC cell proliferation and migration, thereby affecting clinical outcomes.
Highlights
This article is an open access articleHepatocellular carcinoma (HCC), a solid malignant tumor in the liver, ranks the sixth most common cancer type and the third leading cause of malignancies worldwide, with an estimated 800,000 newly diagnosed cases and 780,000 deaths occurring annually [1].The ranking is even higher in Eastern and Southern Asia, including in Taiwan [1]
We aimed to identify any genetic variant that was associated with the co-occurrence of hepatocellular carcinoma (HCC) and transitional cell carcinoma (TCC) double primary cancer (DPC) using a targeted exome sequencing (TES) approach followed by a functional link
4 (26.7%) patients had HCC developed before TCC, 6 (40%) patients had TCC developed before HCC, and 5 (33.3%) patients had both primary cancers diagnosed simultaneously
Summary
This article is an open access articleHepatocellular carcinoma (HCC), a solid malignant tumor in the liver, ranks the sixth most common cancer type and the third leading cause of malignancies worldwide, with an estimated 800,000 newly diagnosed cases and 780,000 deaths occurring annually [1].The ranking is even higher in Eastern and Southern Asia, including in Taiwan [1]. Hepatocellular carcinoma (HCC), a solid malignant tumor in the liver, ranks the sixth most common cancer type and the third leading cause of malignancies worldwide, with an estimated 800,000 newly diagnosed cases and 780,000 deaths occurring annually [1]. Biomedicines 2021, 9, 1819 virus-related and non-viral causes, such as chronic hepatitis B or C infection, alcohol abuse, obesity, and metabolic diseases. Owing to the endeavor of early detection, advances in antiviral therapies for chronic hepatitis B and C, understanding of the oncogenic viral mutants, and success of novel anticancer strategies, survival in patients with HCC has greatly improved in recent years [5,6,7,8]. A large-scale pilot study in Taiwan, including 14,555 patients with HCC, revealed an EHPM rate of
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
