Developing profiles for early pancreatic cancer through bioinformatics analysis

在英国，胰腺癌是癌症相关死亡的第五大原因。统计数据显示，如果肿瘤能够在早期被发现，五年生存率将从3%显著提高到39%(癌症事实和数字，2021年)。然而，由于缺乏针对通常无症状的早期胰腺癌患者的有效和特异的筛查测试，80%以上的胰腺癌病例被诊断为晚期胰腺癌，这突显了在早期发现癌症的敏感和特异标记物的必要性。研究表明，循环肿瘤细胞在胰腺癌的所有阶段仍可被检测到，但不确定的检测率为11%-92%，这取决于用于浓缩的标记物(Martini等人，2019年)；相比之下，对早期胰腺癌进展做出反应的免疫细胞在外周血中表现出明显的特征，可用于非侵入性方式的早期胰腺癌诊断(Pereira等人，2020)。该项目专注于对早期胰腺癌病例产生的外周血液RNA-SEQ数据进行生物信息学分析。我们通过以下列出的独特卖点将我们的技术与其他技术区分开来。(1)与检测肿瘤DNA相比具有更高的灵敏度和特异性(49.5%的准确率；Klein等人，2021年)；(2)使用大型训练数据集来避免年龄、性别、疾病状况(例如糖尿病、胰腺炎)的人口统计学差异；(3)从不同类型的样本(例如血液、活组织检查)和数据(例如RNA、DNA、蛋白质等)中提取新的生物标记物的能力。为了满足独特的诊断需求。我们有以下目标。(1)升级我们的生物信息学软件包，可用于自动分类和预测早期癌症病例(2)在我们的早期采用者同意对我们的产品进行Beta测试的样本中验证产生的生物标志物。(3)申请专利，以保护具有诊断潜力的新生物标记。项目完成后，我们可以将经过验证的生物标记授权给我们的生物技术和临床合作伙伴，以便将诊断产品商业化。这将产生一个明确的临床路径，从血液样本到数据分析，到诊断结果和个性化治疗，以满足胰腺癌患者的个人需求。

Pancreatic cancer is the 5th leading cause of cancer-related death in the UK. Statistics have shown that the five-year survival rate will be markedly increased from 3% to 39% if tumours can be detected at early stages (Cancer Facts & Figures, 2021). However, due to the lack of validated and specific screening tests for early-stage pancreatic cancer patients who are usually asymptomatic, more than 80% of the pancreatic cancer cases are diagnosed at advanced stage, highlighting the needs to identify sensitive and specific markers for detection of the cancer at early stages. Studies have shown that circulating tumour cells remain detectable across all stages of pancreatic cancer, but with an uncertain detection rate of 11%-92% depending on the markers used for enrichment (Martini et al., 2019); in contrast, immune cells that respond to early pancreatic cancer progression exhibit distinct characteristics in peripheral blood and can be exploited for early diagnosis of pancreatic cancer in a non-invasive manner (Pereira et al., 2020).This project focuses on bioinformatics analysis of the peripheral blood RNA-seq data generated from early pancreatic cancer cases. We differentiate our technology from others with the unique selling points listed as follows. (1) High sensitivity and specificity compared to detecting tumour DNA (49.5% accuracy; Klein et al., 2021); (2) Using large training data sets to avoid demographic differences regarding age, sex, disease status (e.g., diabetes, pancreatitis); (3) Ability of extracting novel biomarkers from different types of samples (e.g., blood, biopsy) and data (e.g., RNA, DNA, protein, etc.) to meet unique diagnostic needs.We have the following objectives. (1) Upgrading our bioinformatics software package that can be used to automatically classify and predict early cancer cases (2) Validating the resulting biomarkers in samples from our early adopters who agree to beta test our product. (3) Filing patents to protect the new biomarkers with diagnostic potential.Upon completion of the project, we are able to license the validated biomarkers to our biotech and clinical partners for commercialisation of diagnostic products. This will result in a clear clinical pathway from the blood sample, through data analysis, to diagnostic outcome and personalised therapy that meets the needs of pancreatic cancer patients on an individual basis.