ABSTRACT
The COVID-19 disease, caused by the SARS-Cov-2, presents a heterogeneous clinical spectrum. The risk factors do not fully explain the wide spectrum of disease manifestations, so it is possible that genetic factors could account for novel insights into its pathogenesis. In our previous study, we hypothesized that common variants on chromosome 21, near TMPRSS2 and MX1 genes, may be genetic risk factors associated to the different clinical manifestations of COVID-19. Here, we performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms (SNPs) within TMPRSS2 and near MX1 gene show suggestive associations (P[≤]1x10-5) with severe COVID-19. All five SNPs replicated the association in two independent cohorts of Asian subjects while two and one out of the 5 SNPs replicated in African and Italian populations, respectively (P[≤]0.05). The minor alleles of these five SNPs correlated with a reduced risk of developing severe COVID-19 and increased level of MX1 expression in blood. Our findings provide further evidence that host genetic factors can contribute to determine the different clinical presentations of COVID-19 and that MX1, an antiviral effector of type I and III interferon pathway, may be a potential therapeutic target.
ABSTRACT
Objective@#Uterine serous carcinoma (USC) is a rare highly aggressive disease. In the present study, we aimed to investigate the survival implication of the systematic lymphadenectomy in patients who underwent surgery for apparent early-stage USC. @*Methods@#Consecutive patients with apparent early-stage USC surgically treated at six Italian referral cancer centers were analyzed. A comparison was made between patients who underwent retroperitoneal staging including at least pelvic lymphadenectomy “LND” vs.those who underwent hysterectomy alone “NO-LND”. Baseline, surgical and oncological outcomes were analyzed. Kaplan- Meier curves were calculated for disease-free survival (DFS) and disease-specific survival (DSS). Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). @*Results@#One hundred forty patients were analyzed, 106 LND and 34 NO-LND. NO-LND group (compared to LND group) included older patients (median age, 73 vs.67 years) and with higher comorbidities (median Charlson Comorbidity Index, 6 vs. 5) (p<0.001). No differences in terms of recurrence rate (LND vs. NO-LND, 33.1% vs. 41.4%; p=0.240) were observed. At Cox regression analysis lymphadenectomy did not significantly influence DFS (HR=0.59; 95% confidence interval [CI]=0.32–1.08; p=0.09), and DSS (HR=0.14; 95% CI=0.02–1.21; multivariable analysis p=0.07). Positive node was independently associated with worse DFS (HR=6.22; 95% CI=3.08–12.60; p<0.001) and DSS (HR=5.51; 95% CI=2.31– 13.10; p<0.001), while adjuvant chemotherapy was associated with improved DFS (HR=0.38;95% CI=0.17–0.86; p=0.02) and age was independently associated with worse DSS (HR=1.07;95% CI=1.02–1.13; p<0.001). @*Conclusions@#Although lymphadenectomy did not show survival benefits in patients who underwent surgery for apparent early-stage USC, the presence of lymph node metastasis was the main adverse prognostic factors, supporting the prognostic role of the retroperitoneal staging also in this histological subtype.
ABSTRACT
Objective@#Uterine serous carcinoma (USC) is a rare highly aggressive disease. In the present study, we aimed to investigate the survival implication of the systematic lymphadenectomy in patients who underwent surgery for apparent early-stage USC. @*Methods@#Consecutive patients with apparent early-stage USC surgically treated at six Italian referral cancer centers were analyzed. A comparison was made between patients who underwent retroperitoneal staging including at least pelvic lymphadenectomy “LND” vs.those who underwent hysterectomy alone “NO-LND”. Baseline, surgical and oncological outcomes were analyzed. Kaplan- Meier curves were calculated for disease-free survival (DFS) and disease-specific survival (DSS). Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). @*Results@#One hundred forty patients were analyzed, 106 LND and 34 NO-LND. NO-LND group (compared to LND group) included older patients (median age, 73 vs.67 years) and with higher comorbidities (median Charlson Comorbidity Index, 6 vs. 5) (p<0.001). No differences in terms of recurrence rate (LND vs. NO-LND, 33.1% vs. 41.4%; p=0.240) were observed. At Cox regression analysis lymphadenectomy did not significantly influence DFS (HR=0.59; 95% confidence interval [CI]=0.32–1.08; p=0.09), and DSS (HR=0.14; 95% CI=0.02–1.21; multivariable analysis p=0.07). Positive node was independently associated with worse DFS (HR=6.22; 95% CI=3.08–12.60; p<0.001) and DSS (HR=5.51; 95% CI=2.31– 13.10; p<0.001), while adjuvant chemotherapy was associated with improved DFS (HR=0.38;95% CI=0.17–0.86; p=0.02) and age was independently associated with worse DSS (HR=1.07;95% CI=1.02–1.13; p<0.001). @*Conclusions@#Although lymphadenectomy did not show survival benefits in patients who underwent surgery for apparent early-stage USC, the presence of lymph node metastasis was the main adverse prognostic factors, supporting the prognostic role of the retroperitoneal staging also in this histological subtype.
