Transfer RNA sequencing and application to cancer research and clinics

将 RNA 测序和应用转移到癌症研究和临床

• 批准号: 10705187
• 负责人: Bruce Marc Bissonnette
• 金额: $ 39.72万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705187
• 关键词: Address; Bacteria; Biological; Biological Markers; Biological Models; Biology; Biopsy Specimen; Blood; Blood specimen; Cancer Biology; Cancer Diagnostics; Cancer Etiology; Cancer Patient; Categories; Cells; Cessation of life; Chemotherapy-Oncologic Procedure; Clinic; Clinical; Colorectal Cancer; Colorectal Neoplasms; Colorectal Surgery; Complex; DNA; Data; Detection; Development; Diagnostic Neoplasm Staging; Dimensions; Disease; Environment; Essential Genes; Excision; Family; Feasibility Studies; Feces; Formalin; Gene Expression; Genes; Genetic Code; Genomics; Growth; High-Throughput Nucleotide Sequencing; Higher Order Chromatin Structure; Human; Intestines; Laboratories; Legal patent; Malignant - descriptor; Malignant Neoplasms; Manuscripts; Measures; Metadata; Methods; Microbe; Modification; Morbidity - disease rate; Neoplasm Metastasis; Normal tissue morphology; Operative Surgical Procedures; Pathogenesis; Patient Care; Patient-Focused Outcomes; Patients; Pattern; Performance; Perioperative; Physicians; Physiology; Play; Postoperative Period; Prognosis; Property; Protein Biosynthesis; Proteins; RNA; Recurrence; Recurrent Malignant Neoplasm; Regulation; Reproducibility; Resources; Risk; Risk Assessment; Role; Sampling; Small RNA; Source; Stimulus; Technology; Testing; Therapeutic; Time; Tissue Sample; Toxic effect; Transfer RNA; Transfer RNA Aminoacylation; Treatment outcome; Tumor Biology; Tumor Tissue; aggressive therapy; anticancer research; biobank; biomarker discovery; cancer biomarkers; cancer care; cancer recurrence; cancer risk; cancer surgery; cancer therapy; cell type; chemotherapy; clinical application; clinical care; colon cancer patients; epigenomics; epitranscriptomics; gut bacteria; gut microbes; gut microbiota; high risk; host microbiome; host-microbe interactions; human disease; improved; lens; liquid biopsy; mRNA Translation; microbial; mortality; mouse model; new technology; novel; precision medicine; prevent; prognostic; response; stool sample; tissue fixing; transcriptome; transcriptome sequencing; tumor

Project Abstract Most effective tumor treatments target multiple cellular mechanisms. This proposal will explore a previously under-appreciated cellular mechanism in cancer biology using a newly developed high throughput sequencing technology. Transfer RNAs (tRNAs) are adaptor molecules that read the genetic code for protein biosynthesis. tRNAs are essential for gene expression, an emerging source of cancer-related biomarkers, and a treasure trove of epitranscriptomic marks from both human and disease-associated microbes. tRNAs are dysregulated in many cancers. Due to technical difficulties, tRNA biology and its implications in clinical cancer care have lagged far behind other DNA and RNA-based approaches. We recently developed a new technology called Multiplex Small RNA-seq (MSR-seq) which makes feasible for the first time clinical-scale tRNA studies. Specific Aim 1 will further expand the capability and scope of MSR-seq for clinical samples. Colorectal cancer (CRC) is the second leading cause of cancer-related death in the US. Chemotherapy regimens have not substantively changed in a decade, are unnecessary for 50% of patients, and ineffective in another 30%. Currently there is no way to categorize patients ahead of time. Recent studies provide evidence that gut bacteria can influence growth and metastasis of colorectal tumors. Interactions between tumors and commensal gut microbes provide a new lens to understand the biology of CRC and a new opportunity to identify patients at risk for cancer recurrence and patients who have no need to endure chemotherapy. Specific Aim 2 will apply MSR- seq to screen a biobank of blood, biopsy, and stool samples from CRC patients, and to study a murine model of CRC recurrence. This combination of a unique biobank with a new technology has potential to transform how CRC is treated and explores the complex host-microbe interactions in a human disease.

项目摘要 最有效的肿瘤治疗靶向多种细胞机制。该提案将探讨 使用新开发的高通量技术， 测序技术转移RNA（tRNA）是一种衔接分子，它可以读取蛋白质的遗传密码， 生物合成tRNA是基因表达所必需的，是癌症相关生物标志物的新兴来源， 人类和疾病相关微生物的表观标记宝库。trna的 在许多癌症中失调。由于技术上的困难，tRNA生物学及其在临床癌症中的意义 护理远远落后于其他基于DNA和RNA的方法。我们最近开发了一种新技术 这种技术被称为多重小RNA测序（MSR-seq），它首次使临床规模的tRNA研究成为可能。 具体目标1将进一步扩大MSR-seq用于临床样本的能力和范围。结直肠癌 (CRC)是美国癌症相关死亡的第二大原因。化疗方案没有 在十年内发生了实质性变化，对50%的患者来说是不必要的，对另外30%的患者无效。 目前还没有办法提前对患者进行分类。最近的研究提供了证据， 可影响结直肠肿瘤的生长和转移。肿瘤与胃肠的相互作用 微生物提供了一个新的透镜来了解CRC的生物学和一个新的机会，以确定患者的风险 用于癌症复发和不需要忍受化疗的患者。具体目标2将适用MSR- seq筛选来自CRC患者的血液、活检和粪便样本的生物库，并研究CRC的小鼠模型。 CRC复发。这种独特的生物库与新技术的结合有可能改变 CRC是治疗和探索人类疾病中复杂的宿主-微生物相互作用。