Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancer

Abstract We aimed to create a NK cell marker genes-based signature to predict immunotherapy response and prognosis in colorectal cancer. We integrated scRNA-seq data from four Gene Expression Omnibus (GEO) samples and performed Weighted gene correlation network analysis (WGCNA) based on 587 the Canc...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiaoyu Qin, Wenjuan Xu, Jinxiu Wu, Ming Li
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-025-01842-7
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1823861793345241088
author Xiaoyu Qin
Wenjuan Xu
Jinxiu Wu
Ming Li
author_facet Xiaoyu Qin
Wenjuan Xu
Jinxiu Wu
Ming Li
author_sort Xiaoyu Qin
collection DOAJ
description Abstract We aimed to create a NK cell marker genes-based signature to predict immunotherapy response and prognosis in colorectal cancer. We integrated scRNA-seq data from four Gene Expression Omnibus (GEO) samples and performed Weighted gene correlation network analysis (WGCNA) based on 587 the Cancer Genome Atlas (TCGA) colorectal cancer samples to uncover NK cell-related genes. We identified 1080 NK cell-related core genes and 276 NK cell-related feature genes based on WGCNA and clustering and annotation of scRNA-seq data, respectively. Six key NK cell-related prognostic signature genes were obtained by univariate and LASSO regression analyses, including ADAM8, CTSD, CCL4, IL2RB, TTC38, and PLEK. Two validation cohorts from the GEO dataset, comprising 124 and 201 samples respectively, were used. The signature was significantly associated with overall survival and correlated with immune cell infiltration, immune and stromal scores, and immune checkpoint genes. Furthermore, the signature was associated with the homologous recombination deficiency (HRD) and T-cell receptor (TCR) scores. In conclusion, our study proposes a new prognostic signature based on NK cell marker genes, which may serve as a potential tool to predict overall survival and immunotherapy response for CRC patients.
format Article
id doaj-art-3d6f73f24804497eace2618ed4a03a8a
institution Kabale University
issn 2730-6011
language English
publishDate 2025-02-01
publisher Springer
record_format Article
series Discover Oncology
spelling doaj-art-3d6f73f24804497eace2618ed4a03a8a2025-02-09T12:43:28ZengSpringerDiscover Oncology2730-60112025-02-0116111610.1007/s12672-025-01842-7Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancerXiaoyu Qin0Wenjuan Xu1Jinxiu Wu2Ming Li3Department of Gastroenterology, Shanghai Pudong New Area Gongli HospitalDepartment of General Surgery, Shanghai Punan HospitalDepartment of General Surgery, Shanghai Punan HospitalDepartment of General Surgery, Shanghai Punan HospitalAbstract We aimed to create a NK cell marker genes-based signature to predict immunotherapy response and prognosis in colorectal cancer. We integrated scRNA-seq data from four Gene Expression Omnibus (GEO) samples and performed Weighted gene correlation network analysis (WGCNA) based on 587 the Cancer Genome Atlas (TCGA) colorectal cancer samples to uncover NK cell-related genes. We identified 1080 NK cell-related core genes and 276 NK cell-related feature genes based on WGCNA and clustering and annotation of scRNA-seq data, respectively. Six key NK cell-related prognostic signature genes were obtained by univariate and LASSO regression analyses, including ADAM8, CTSD, CCL4, IL2RB, TTC38, and PLEK. Two validation cohorts from the GEO dataset, comprising 124 and 201 samples respectively, were used. The signature was significantly associated with overall survival and correlated with immune cell infiltration, immune and stromal scores, and immune checkpoint genes. Furthermore, the signature was associated with the homologous recombination deficiency (HRD) and T-cell receptor (TCR) scores. In conclusion, our study proposes a new prognostic signature based on NK cell marker genes, which may serve as a potential tool to predict overall survival and immunotherapy response for CRC patients.https://doi.org/10.1007/s12672-025-01842-7Colorectal cancerNatural killer cellsScRNA-seqImmunotherapy responsePrognosis
spellingShingle Xiaoyu Qin
Wenjuan Xu
Jinxiu Wu
Ming Li
Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancer
Discover Oncology
Colorectal cancer
Natural killer cells
ScRNA-seq
Immunotherapy response
Prognosis
title Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancer
title_full Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancer
title_fullStr Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancer
title_full_unstemmed Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancer
title_short Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancer
title_sort integration of single cell and bulk rna sequencing data to construct and validate a signature based on nk cell marker genes to predict immunotherapy response and prognosis in colorectal cancer
topic Colorectal cancer
Natural killer cells
ScRNA-seq
Immunotherapy response
Prognosis
url https://doi.org/10.1007/s12672-025-01842-7
work_keys_str_mv AT xiaoyuqin integrationofsinglecellandbulkrnasequencingdatatoconstructandvalidateasignaturebasedonnkcellmarkergenestopredictimmunotherapyresponseandprognosisincolorectalcancer
AT wenjuanxu integrationofsinglecellandbulkrnasequencingdatatoconstructandvalidateasignaturebasedonnkcellmarkergenestopredictimmunotherapyresponseandprognosisincolorectalcancer
AT jinxiuwu integrationofsinglecellandbulkrnasequencingdatatoconstructandvalidateasignaturebasedonnkcellmarkergenestopredictimmunotherapyresponseandprognosisincolorectalcancer
AT mingli integrationofsinglecellandbulkrnasequencingdatatoconstructandvalidateasignaturebasedonnkcellmarkergenestopredictimmunotherapyresponseandprognosisincolorectalcancer