Role of zinc transporter LIV-1 protein in high-grade serous ovarian cancer

Le carcinome séreux de haut grade (HGSC) de l'ovaire est le cancer gynécologique le plus létal. Bien que les découvertes récentes aient fait progresser notre compréhension de l'agressivité du HGSC, les mécanismes moléculaires impliqués dans le développement de ce cancer demeurent peu clairs. L'une des principales caractéristiques des tumeurs agressives est leur capacité à métastaser. En général, les cancers épithéliaux de l'ovaire se propagent par extension locale, invasion lymphatique et implantation intrapéritonéale. Des études ont suggéré que la protéine LIV-1, un transporteur de zinc, joue un rôle important dans la formation de métastases dans différents tissus. Néanmoins, aucune étude ne rapporte le rôle de LIV-1 dans les métastases du HGSC. Nous avons donc étudié l’impact de LIV-1 sur le potentiel invasif et migratoire des cellules HGSC. Nous avons observé des niveaux d'expression variables du gène et de la protéine LIV-1 dans 14 lignées cellulaires du HGSC. Bien qu'une corrélation positive ait été observée entre l'expression du gène et les quantités de protéine LIV-1, cette corrélation n'était pas forte et non significative. Nous avons par ailleurs choisi cinq lignées cellulaires pour effectuer des tests biologiques, en fonction de leurs niveaux protéiques: TOV3133G et TOV2295(R) (haute), TOV2978G (moyenne), et TOV1369 et OV866 (2) (faible). Nous avons trouvé qu'il y avait une forte et significative corrélation positive entre les niveaux de LIV-1 et le potentiel invasif de ces cellules HGSC (R2 = 0.8666, p = 0.0216), mais une faible corrélation négative (non significative) avec le potentiel de migration (R2 = 0.4514, p = 0.2142). Des expériences d'ARNi ont montré qu'une expression réduite de la protéine LIV-1 inhibe la capacité invasive. Cependant, aucune différence significative n'a été observée en ce qui concerne la capacité de migration. Nos résultats suggèrent que LIV-1 joue un rôle positif dans la progression tumorale de HGSC. Nous avons démontré que LIV-1 est impliqué dans l'invasion in vitro mais pas dans la migration des cellules HGSC, et que son expression est associée aux formes les plus avancées du cancer de l'ovaire, suggérant que LIV-1 pourrait être un marqueur potentiel de l'agressivité tumoraleHigh-grade serous carcinoma (HGSC) of the ovary is the most lethal gynecological cancer. Although recent progress has advanced our understanding in the aggressiveness of HGSC, the molecular mechanisms involved in the development of this cancer remain unclear. One of the main features of aggressive tumours is their ability to metastasize. In general, epithelial ovarian cancers (EOCs) spread through local extension, lymphatic invasion, and intraperitoneal implantation. Studies have suggested that the zinc transporter LIV-1 protein has an important role in tumour metastasis in different tissues. However, there are no reports on the role of LIV-1 in HGSC metastasis. We investigated the role of LIV-1 in the invasive and migration potential of HGSC cells. We observed variable expression levels of the LIV-1 gene and protein in 14 HGSC cell lines. Although a positive correlation was observed between the gene expression and the quantities of LIV-1 protein, this correlation was not strong and not significant; thus, we chose five cell lines to perform biological assays, based on their protein levels: TOV3133G and TOV2295(R) (high), TOV2978G (medium), and TOV1369 and OV866(2) (low). We found that there was a strong and significant positive correlation between LIV-1 levels and the invasive potential of these HGSC cells (R2 = 0.8666, p = 0.0216), but a weak and negative correlation (not significant) with their migration potential (R2 = 0.4514, p = 0.2142). RNAi experiments demonstrated that reduced LIV-1 expression inhibits invasive capacity; however, no significant differences were observed in regard to migration capacity. Our results suggest that LIV-1 has a positive role in favouring the tumour progression of HGSC. We have demonstrated that LIV-1 is involved in the in vitro invasion but not migration of HGSC cells, and that its expression is associated with more aggressive ovarian cancers,suggesting LIV-1 as a potential marker for tumour aggressiveness

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population