Construction and Validation of a Novel T/NK-Cell Prognostic Signature for Pancreatic Cancer Based on Single-Cell RNA Sequencing.

IF 1.8 4区医学 Q3 ONCOLOGY

Cancer Investigation Pub Date : 2024-11-01 Epub Date: 2024-11-10 DOI:10.1080/07357907.2024.2424328

Yu Wang, Cong Zhang, Jianlu Zhang, Haoran Huang, Junchao Guo

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引用次数: 0

Abstract

Background: Evidence with regards to the distinction between primary and metastatic tumors in pancreatic cancer and driving factors for metastases remains limited.

Methods: Single-cell RNA sequencing (scRNA-seq) was conducted on metastatic pancreatic cancer. Bioinformatics analysis on relevant sequencing data was used to construct a risk model to predict patient prognosis. Furthermore, immune infiltration and metabolic differences were assessed. The biological function of key differential genes was evaluated.

Results: Paired primary and metastatic tumor tissues from 3 pancreatic cancer patients were collected and conducted scRNA-seq. Subsequently, the T/NK cell subgroup was the most different cell type between primary tumors and liver metastases and was selected for further analysis. Eventually, 6 specifically expressed genes of T/NK cells (B2M, ZFP36L2, ANXA1, ARL4C, TSPYL2, FYN) were used constructing the prognostic model. The stability of this model was validated by an external cohort. Meanwhile, different immune infiltration abundances occurred between high and low risk groups stratified by the model. The high-risk group had a stronger metabolic capability.

Conclusions: A novel prognostic T/NK-cell signature for pancreatic cancer was constructed based on scRNA-seq data and externally validated. The involved key genes may play a role in multiple metabolic pathways of metastasis and affect the tumor immune microenvironment.

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基于单细胞 RNA 测序的新型胰腺癌 T/NK 细胞预后特征的构建与验证

背景：有关胰腺癌原发性和转移性肿瘤的区别以及转移的驱动因素的证据仍然有限：方法：对转移性胰腺癌进行了单细胞RNA测序（scRNA-seq）。方法：对转移性胰腺癌进行了单细胞 RNA 测序（scRNA-seq），并对相关测序数据进行了生物信息学分析，从而构建了预测患者预后的风险模型。此外，还评估了免疫浸润和代谢差异。对关键差异基因的生物功能进行了评估：收集了 3 名胰腺癌患者的配对原发性和转移性肿瘤组织，并进行了 scRNA-seq。随后，T/NK 细胞亚群是原发肿瘤和肝转移瘤之间差异最大的细胞类型，被选中进行进一步分析。最终，6个T/NK细胞特异表达基因（B2M、ZFP36L2、ANXA1、ARL4C、TSPYL2、FYN）被用于构建预后模型。该模型的稳定性通过外部队列进行了验证。同时，根据模型分层的高风险组和低风险组之间出现了不同的免疫浸润丰度。结论：一种新的T/N细胞预后模型可用于预测癌症患者的预后：结论：基于 scRNA-seq 数据构建了一个新的胰腺癌 T/NK 细胞预后特征，并通过了外部验证。结论：基于 scRNA-seq 数据构建了一种新的胰腺癌 T/NK 细胞预后特征，并进行了外部验证，其中涉及的关键基因可能在多种转移代谢途径中发挥作用，并影响肿瘤免疫微环境。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Investigation 医学-肿瘤学

CiteScore

3.80

自引率

4.20%

发文量

审稿时长

8.5 months

期刊介绍： Cancer Investigation is one of the most highly regarded and recognized journals in the field of basic and clinical oncology. It is designed to give physicians a comprehensive resource on the current state of progress in the cancer field as well as a broad background of reliable information necessary for effective decision making. In addition to presenting original papers of fundamental significance, it also publishes reviews, essays, specialized presentations of controversies, considerations of new technologies and their applications to specific laboratory problems, discussions of public issues, miniseries on major topics, new and experimental drugs and therapies, and an innovative letters to the editor section. One of the unique features of the journal is its departmentalized editorial sections reporting on more than 30 subject categories covering the broad spectrum of specialized areas that together comprise the field of oncology. Edited by leading physicians and research scientists, these sections make Cancer Investigation the prime resource for clinicians seeking to make sense of the sometimes-overwhelming amount of information available throughout the field. In addition to its peer-reviewed clinical research, the journal also features translational studies that bridge the gap between the laboratory and the clinic.