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Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer

2026年11月2日更新者：Yong Yang、Fujian Medical University Union Hospital

A Prospective Observational Study of Tumour Microenvironment Remodelling During Neoadjuvant Therapy in Locally Advanced Rectal Cancer Using Single-Cell and Spatial Multi-omics

This prospective observational study characterises the tumour immune microenvironment and microbial ecology of locally advanced rectal cancer before and during neoadjuvant therapy. Tumour tissue and peripheral blood are profiled by whole-genome sequencing, single-cell RNA sequencing with paired T-cell and B-cell receptor repertoire sequencing, spatial transcriptomics of formalin-fixed paraffin-embedded sections, multiplex immunofluorescence, and blood-based proteomic, cytokine and bulk T-cell receptor analyses. The study examines how immune and stromal states change during treatment and how they relate to major pathological response.

研究概览

地位

招聘中

条件

直肠肿瘤

详细说明

Locally advanced rectal cancer is increasingly treated with total neoadjuvant therapy combining short-course radiotherapy, chemotherapy and programmed cell death protein 1 (PD-1) blockade, but the effect of treatment sequence on the tumour microenvironment is unresolved, and few patients have been profiled with matched pre- and on-treatment single-cell data. In this observational study, we collect tumour tissue and peripheral blood from patients with locally advanced rectal cancer at baseline, before any neoadjuvant treatment, and again after completion of short-course hypofractionated radiotherapy (5 Gy in 5 fractions) followed by one cycle of chemo-immunotherapy, together with archival formalin-fixed paraffin-embedded tissue where available. Additional formalin-fixed paraffin-embedded specimens from treatment-naive patients undergoing primary surgery, and from end-of-treatment biopsies, are used as controls for the spatial analyses. Fresh tumour tissue is analysed by whole-genome sequencing and by single-cell RNA sequencing with paired T-cell and B-cell receptor repertoire sequencing. Formalin-fixed paraffin-embedded tissue is analysed by spatial transcriptomics and multiplex immunofluorescence. Peripheral blood mononuclear cells are analysed by bulk T-cell receptor repertoire sequencing, and plasma or serum by proteomic and cytokine profiling where material permits. The principal clinical endpoint is major pathological response (mPR) at resection. We examine changes in immune and stromal populations between baseline and the on-treatment time point, features of the immune microenvironment associated with mPR, and, as exploratory analyses, the tumour microbial ecology associated with response together with differences between neoadjuvant treatment sequences. Analyses are descriptive and hypothesis-generating; no intervention, treatment assignment or change in clinical care is involved. The study was approved by the Ethics Committee of Fujian Medical University Union Hospital (2024KY297, approved 30 December 2024; and 2024KJCX060, approved 18 September 2024); archival specimens are used under a waiver of additional informed consent, and fresh biopsy or surgical tissue and blood are collected with written informed consent.

研究类型

观察性的

注册 (估计的)

100

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

姓名：Wan-cai Que
电话号码：0086-0591-86218304
邮箱：xhyyjgb@163.com

学习地点

中国
- Fujian
  - Fuzhou、Fujian、中国、350001
    - 招聘中
    - Fujian Medical University Union Hospital

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

孩子
成人
年长者

接受健康志愿者

不

有资格学习的性别

全部

取样方法

非概率样本

研究人群

Patients with locally advanced rectal adenocarcinoma treated at Fujian Medical University Union Hospital, China, from whom tumour tissue and peripheral blood were collected before and during neoadjuvant therapy.

描述

Inclusion Criteria:

Age 18 to 75 years
Eastern Cooperative Oncology Group performance status 0-1
Histologically confirmed rectal adenocarcinoma
Locally advanced disease staged as cT3-T4N0 or cT2-T4N+ without distant metastasis (AJCC 8th edition)
Lower border of the tumour within 10 cm of the anal verge
Scheduled to receive neoadjuvant therapy followed by surgery, with tumour tissue and peripheral blood available before and during neoadjuvant therapy
Written informed consent for fresh biopsy or surgical tissue, or a waiver granted by the institutional ethics committee for archival specimens

Exclusion Criteria:

Insufficient tissue or nucleic acid quality for the planned profiling assays
Incomplete clinical records precluding assessment of pathological or clinical response
A history of other malignancy within 5 years other than adequately treated carcinoma in situ or basal cell carcinoma

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

观测模型：COHORT
时间观点：PROSPECTIVE

团体/队列数

队列和干预

团体/队列
Achieved pathological or clinical complete response Patients whose resection specimen showed a pathological complete response (ypT0N0) or who achieved a sustained clinical complete response, from whom pre-treatment and on-treatment tissue and blood were profiled.
Did not achieve pathological or clinical complete response Patients with residual viable tumour at resection or without a sustained clinical complete response, from whom pre-treatment and on-treatment tissue and blood were profiled.

研究衡量的是什么？

主要结果指标

结果测量	措施说明	大体时间
Change in immune and stromal cell composition in tumour tissue during neoadjuvant therapy 大体时间：Baseline (before treatment) and week 4 after treatment initiation	Cell-type composition and transcriptional states of T, natural killer (NK), B and myeloid populations and of stromal subsets before treatment and during neoadjuvant therapy, determined by single-cell RNA sequencing.	Baseline (before treatment) and week 4 after treatment initiation
Major pathological response (mPR) and its association with immune microenvironment features 大体时间：Through study completion, an average of 4 years	Proportion of patients achieving major pathological response, defined as 10% or less residual viable tumour at resection, and the association of pre-treatment and on-treatment immune microenvironment features with mPR.	Through study completion, an average of 4 years

次要结果测量

结果测量	措施说明	大体时间
Transcriptional states of immune populations before and during treatment 大体时间：Baseline (before treatment) and week 4 after treatment initiation	Exhaustion, activation and memory programmes of T and NK cells and B-cell states, determined by single-cell RNA sequencing with paired T-cell and B-cell receptor repertoire sequencing.	Baseline (before treatment) and week 4 after treatment initiation
Spatial organisation of tumour and immune compartments before and during treatment 大体时间：Baseline (before treatment) and week 4 after treatment initiation	Spatial distribution of tumour, immune and stromal compartments determined by spatial transcriptomics of formalin-fixed paraffin-embedded sections and multiplex immunofluorescence, compared with specimens from treatment-naive patients undergoing primary surgery and from end-of-treatment biopsies as controls.	Baseline (before treatment) and week 4 after treatment initiation
Comparison of microenvironment remodelling between neoadjuvant treatment sequences 大体时间：Through study completion, an average of 4 years	Between-group comparison of the change in tumour microenvironment composition between baseline and week 4, expressed as the percentage of cluster of differentiation 8 (CD8)-positive T cells, NK cells, B cells and plasma cells among all cells measured by single-cell RNA sequencing, in patients receiving radiotherapy before versus after chemo-immunotherapy.	Through study completion, an average of 4 years
Somatic genomic alterations associated with response to neoadjuvant therapy 大体时间：Baseline (before treatment) and week 4 after treatment initiation	Somatic mutations, copy-number alterations and mutational signatures determined by whole-genome sequencing of tumour tissue before and during neoadjuvant therapy.	Baseline (before treatment) and week 4 after treatment initiation
Clonal diversity of the peripheral blood T-cell receptor repertoire 大体时间：Baseline (before treatment) and week 4 after treatment initiation	Diversity and distribution of T-cell receptor clonotypes in peripheral blood mononuclear cells, expressed as the Shannon diversity index and the proportion of expanded clonotypes, measured by bulk T-cell receptor repertoire sequencing.	Baseline (before treatment) and week 4 after treatment initiation
Correlation of tumour microbial composition with major pathological response 大体时间：Baseline (before treatment) and week 4 after treatment initiation	Correlation between the relative abundance of tumour-associated bacterial taxa, expressed as the percentage of sequencing reads assigned to each taxon measured by small-subunit ribosomal RNA gene sequencing or shotgun metagenomic sequencing of tumour tissue, and major pathological response, expressed as the percentage of patients with 10% or less residual viable tumour at resection (exploratory).	Baseline (before treatment) and week 4 after treatment initiation
Plasma protein and cytokine concentrations before and during neoadjuvant therapy 大体时间：Baseline (before treatment) and week 4 after treatment initiation	Concentrations of plasma or serum proteins and cytokines, expressed in pg/mL, measured by multiplex proteomic and cytokine assays.	Baseline (before treatment) and week 4 after treatment initiation

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Fujian Medical University Union Hospital

调查人员

研究主任：Jian Liu (jianliu@nankai.edu.cn), PhD、Nankai University

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2025年1月1日

初级完成 (估计的)

2028年12月31日

研究完成 (估计的)

2028年12月31日

研究注册日期

首次提交

2026年10月27日

首先提交符合 QC 标准的

2026年11月2日

首次发布 (实际的)

2026年11月6日

研究记录更新

最后更新发布 (实际的)