Immunogenicity of two doses of BNT162b2 and mRNA-1273 vaccines for solid cancer patients on treatment with or without a previous SARS-CoV-2 infection

Previous studies on the immunogenicity of SARS-CoV-2 mRNA vaccines showed a reduced seroconversion in cancer patients. The aim of our study is to evaluate the immunogenicity of two doses of mRNA vaccines in solid cancer patients with or without a previous exposure to the virus. This is a single-institution, prospective, nonrandomized study. Patients in active treatment and a control cohort of healthy people received two doses of BNT162b2 (Comirnaty, BioNTech/Pfizer, The United States) or mRNA-1273 (Spikevax, Moderna). Vaccine was administered before starting anticancer therapy or on the first day of the treatment cycle. SARS-CoV-2 antibody levels against S1, RBD (to evaluate vaccine response) and N proteins (to evaluate previous infection) were measured in plasma before the first dose and 30 days after the second one. From January to June 2021, 195 consecutive cancer patients and 20 healthy controls were enrolled. Thirty-one cancer patients had a previous exposure to SARS-CoV-2. Cancer patients previously exposed to the virus had significantly higher median levels of anti-S1 and anti-RBD IgG, compared to healthy controls (P = .0349) and to cancer patients without a previous infection (P < .001). Vaccine type (anti-S1: P < .0001; anti-RBD: P = .0045), comorbidities (anti-S1: P = .0274; anti-RBD: P = .0048) and the use of G-CSF (anti-S1: P = .0151) negatively affected the antibody response. Conversely, previous exposure to SARS-CoV-2 significantly enhanced the response to vaccination (anti-S1: P < .0001; anti-RBD: P = .0026). Vaccine immunogenicity in cancer patients with a previous exposure to SARS-CoV-2 seems comparable to that of healthy subjects. On the other hand, clinical variables of immune frailty negatively affect humoral immune response to vaccination.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

长链非编码RNA与mRNA在胰腺癌中的差异表达及其预后价值

目的：对基因芯片表达汇编（GEO）数据库和癌症基因组图谱（TCGA）数据库中的胰腺癌数据进行生物信息学分析，探讨长链非编码RNA （lncRNA）与mRNA在胰腺癌中的差异表达和预后价值。方法：首先对GEO数据库中的胰腺癌数据注释获得mRNA和lncRNA，并对芯片中的mRNA和lncRNA取交集获得差异mRNA和lncRNA。然后对差异mRNA和lncRNA进行基因分析，同时对TCGA数据库中胰腺癌的相关数据进行生存分析。结果：通过基因分析获得与胰腺癌相关可信度高的差异mRNA 1 147个，lncRNA 336个，通过基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，构建lncRNA-mRNA共表达网络、lncRNA-mRNA-pathway网络、信号通路关系网络及蛋白质相互作用网络，结果证明mRNA和lncRNA对胰腺癌的发生发展有着重要影响；生存分析发现有12个lncRNA与胰腺癌的预后相关，分别是ATP1A1-AS1、CBR3-AS1、CTD-3080P12.3、FAM66D、FAM87A、FLJ38576、LINC00476、LINC00574、LINC01554、PYY2、LINC00857、OVOL1-AS1。结论：lncRNA对胰腺癌的发生发展及预后有显著影响，有望为胰腺癌的靶向治疗和预后评估提供新的治疗靶点和分子标志物。     

胃癌患者根治术后腹腔灌洗液中CEA mRNA表达的临床意义

目的：探讨胃癌患者根治术后腹腔冲洗液中CEA mRNA表达情况及其临床意义。方法: 回顾性分析了2013 年1 月至2017 年12 月在南京大学医学院附属鼓楼医院接受胃癌根治切除术后进行腹腔灌洗液CEA mRNA检测的139 名患者的病历资料，并进行术后常规随访。用RT-PCR检测139 胃癌患者根治术后腹腔灌洗液中CEA mRNA表达情况。卡方检验分析腹腔灌洗液中CEA mRNA表达与临床基本特征、组织病理学资料、血液学指标及复发方式之间的关系。采用Logistic 单因素及多因素回归分析筛查影响CEA mRNA表达水平的因素。结果：139 名患者中44 名（31.7%）患者腹腔灌洗液CEA mRNA阳性。分析显示，胃癌患者腹腔灌洗液CEA mRNA阳性表达与性别、年龄、病理分级、Lauren 分型和HER2、EGFR、VEGFR等标记物间均没有明显的关联（均P>0.05），与病理类型、脉管是否侵犯、局部浸润深度、淋巴结转移程度和临床AJCC 分期有明显的关联（均P<0.05）。CEA mRNA阳性患者腹膜复发率明显高于阴性患者（P=0.012）。Logistic 单因素回归分析显示，印戒细胞癌（P=0.04，HR=2.810，95% CI: 1.050~7.520）、T 分期（P=0.016，HR=6.329，95% CI: 1.417~28.264）、N 分期（P=0.022，HR=3.068，95% CI: 1.172~8.027）、AJCC分期（P=0.016 ，HR=3.971 ，95% CI: 1.295~12.173 ）、神经侵犯（P=0.002 ，HR=6.738，95% CI: 1.995~22.757）、脉管侵犯（P<0.001，HR=16.36，95% CI: 3.85~69.512）为胃癌患者腹腔灌洗液CEA mRNA阳性表达的危险因素。Logistic 多因素回归分析显示，经过对其他因素的校正，脉管侵犯（P<0.001，HR=21.314，95% CI: 4.21~107.907）为胃癌患者腹腔灌洗液CEA mRNA阳性表达的独立危险因素。结论：胃癌腹腔灌洗CEA mRNA阳性的患者腹膜复发转移风险高且预后不良，应考虑包括腹腔局部治疗在内的更加积极的抗肿瘤治疗。     

The value of mRNA expression of S100A8 and S100A9 as blood-based biomarkers of inflammatory bowel disease

Background and study aimsNon-invasive biomarkers of inflammatory bowel diseases (IBD) are of critical importance. Here, we evaluated the S100A8 and S100A9 mRNA expression, as the heterodimers of calprotectin, in the blood leucocytes of IBD patients to find how their expression associates with the disease characteristics.Patients and methodsIn this cross-sectional study, 59 IBD patients and 30 healthy subjects were included. The flare and remission phases of disease were identified in 46 and 13 patients, respectively. Blood leucocytes were isolated, and the S100A8 and S100A9 mRNA expression were evaluated in the isolated leucocytes using relative quantification real-time PCR.ResultsThe mean S100A8 and S100A9 mRNA expression were significantly higher in IBD patients than in the controls (p = 0.03 and p = 0.02, respectively). The mean S100A8 and S100A9 mRNA expression were significantly higher in the flare phase of the disease compared with the remission phase (p = 0.01 and p = 0.007, respectively). S100A8 distinguished IBD patients from controls with the sensitivity and specificity of 73% and 64%, and flare phase of disease from remission with the sensitivity and specificity of 67% and 62%. On the other hand, S100A9 distinguished IBD patients from controls with the sensitivity and specificity of 81% and 70%, and flare phase of disease from remission with the sensitivity and specificity of 68% and 64%.ConclusionThe S100A8 and S100A9 mRNA are differentially expressed in blood leucocytes of IBD patients compared to healthy controls as well as active versus quiescent disease. Thus, they can be potentially used as a blood-based biomarker in the monitoring of IBD.