Find in Library

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 <i>Spectrin Repeat Containing Nuclear Envelope Protein 1</i> (<i>SYNE1</i>) gene was associated with DPC occurrence (<i>p</i> = 0.002), compared with that in the healthy population. Further independent cohort verification analysis revealed that the <i>SYNE1</i>-rs9479297-TT genotype (versus TC + CC genotypes) was enriched in patients with DPC, compared with that in those with TCC alone (<i>p</i> = 0.039), those with HCC alone (<i>p</i> = 0.006), those with non-HCC/non-TCC (<i>p</i> < 0.001), and healthy population (<i>p</i> < 0.001). <i>SYNE1</i> mRNA expression reduced in both patients with HCC and TCC, and its lower expression in HCC was associated with shorter recurrence-free (<i>p</i> = 0.0314) and metastasis-free (<i>p</i> = 0.0479) survival. <i>SYNE1</i>-rs9479297 genotypes were correlated with tissue SYNE1 levels and clinical outcomes in HCC patients. Finally, <i>SYNE1</i> silencing enhanced the cell proliferation and migration of HCC/TCC cells. In conclusion, <i>SYNE1</i>-rs9479297 genotypes were associated with HCC/TCC DPC co-occurrence and correlated with <i>SYNE1</i> expression, which in turn contributed to HCC/TCC cell proliferation and migration, thereby affecting clinical outcomes.