SYNE1 Exonic Variant rs9479297 Contributes to Concurrent Hepatocellular and Transitional Cell Carcinoma Double Primary Cancer

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 sequ...

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Bibliographic Details
Published in:Biomedicines 2021-12, Vol.9 (12), p.1819
Main Authors: Chu, Yu-De, Kee, Kwong-Ming, Lin, Wey-Ran, Lai, Ming-Wei, Lu, Sheng-Nan, Chung, Wen-Hung, Pang, See-Tong, Yeh, Chau-Ting
Format: Article
Language:English
Subjects:
Bladder
Cell growth
Cell migration
Cell proliferation
Cloning
Gene expression
Genetic diversity
Genotypes
Hepatitis
Hepatocellular carcinoma
Liver cancer
Metastases
Patients
Polymerase chain reaction
single nucleotide polymorphism
Spectrin
spectrin repeat containing nuclear envelop protein 1
targeted exome sequencing
Transitional cell carcinoma
Urogenital system
Viral envelope proteins
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Summary: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 ( ) gene was associated with DPC occurrence ( = 0.002), compared with that in the healthy population. Further independent cohort verification analysis revealed that the -rs9479297-TT genotype (versus TC + CC genotypes) was enriched in patients with DPC, compared with that in those with TCC alone ( = 0.039), those with HCC alone ( = 0.006), those with non-HCC/non-TCC ( < 0.001), and healthy population ( < 0.001). mRNA expression reduced in both patients with HCC and TCC, and its lower expression in HCC was associated with shorter recurrence-free ( = 0.0314) and metastasis-free ( = 0.0479) survival. -rs9479297 genotypes were correlated with tissue SYNE1 levels and clinical outcomes in HCC patients. Finally, silencing enhanced the cell proliferation and migration of HCC/TCC cells. In conclusion, -rs9479297 genotypes were associated with HCC/TCC DPC co-occurrence and correlated with expression, which in turn contributed to HCC/TCC cell proliferation and migration, thereby affecting clinical outcomes.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9121819