Effects of NK cell-related lncRNA on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinoma

BackgroundPatients with pancreatic ductal adenocarcinoma (PDAC) face a highly unfavorable outcome and have a poor response to standard treatments. Immunotherapy, especially therapy based on natural killer (NK) cells, presents a promising avenue for the treatment of PDAC.AimsThis research endeavor se...

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Main Authors: Jinze Li, Chuqi Xia, Yuxuan Li, Hanhan Liu, Cheng Gong, Daoming Liang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514259/full
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author Jinze Li
Chuqi Xia
Yuxuan Li
Hanhan Liu
Cheng Gong
Daoming Liang
author_facet Jinze Li
Chuqi Xia
Yuxuan Li
Hanhan Liu
Cheng Gong
Daoming Liang
author_sort Jinze Li
collection DOAJ
description BackgroundPatients with pancreatic ductal adenocarcinoma (PDAC) face a highly unfavorable outcome and have a poor response to standard treatments. Immunotherapy, especially therapy based on natural killer (NK) cells, presents a promising avenue for the treatment of PDAC.AimsThis research endeavor seeks to formulate a predictive tool specifically designed for PDAC based on NK cell-related long non-coding RNA (lncRNA), revealing new molecular subtypes of PDAC to promote personalized and precision treatment.MethodsUtilizing the Tumor Immune Single-cell Hub 2 platform, we discovered genes associated with NK cells in PDAC. We employed the TCGA-PAAD dataset to ascertain the expression profiles of these NK cell-related genes and to screen for lncRNAs correlated with NK cells. Subsequently, we utilized Cox regression analysis for hazard ratios and LASSO regression analysis to identify three NK cell-related lncRNAs that were used to develop a prognostic assessment model. The forecasting accuracy of this model was appraised using the ROC curve and validated using a test set and the complete dataset.ResultsSuccessful construction of a prognostic model comprising three lncRNAs was achieved, demonstrating good predictive efficiency in the training set, validation dataset, and the entire dataset. NK cells display robust interactions with malignant cells, CD8 T cells, and fibroblasts in the PDAC tumor microenvironment and participate in the transport of various signaling molecules and following immune responses in PDAC. According to the expression patterns of NK cell-related lncRNA, we labeled PDAC patients as four molecular subtypes, exhibiting significant differences in immune cell infiltration, drug sensitivity, and other aspects.ConclusionThis study Uncovered the activity of NK cells within PDAC, proposed an NK cell-related lncRNA model, and delineated new molecular subtypes, thereby providing targets for personalized therapy.
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spelling doaj-art-3907f1368b554e28ad4c619e5e75b5a92025-01-13T06:11:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15142591514259Effects of NK cell-related lncRNA on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinomaJinze Li0Chuqi Xia1Yuxuan Li2Hanhan Liu3Cheng Gong4Daoming Liang5Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Pathology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaBackgroundPatients with pancreatic ductal adenocarcinoma (PDAC) face a highly unfavorable outcome and have a poor response to standard treatments. Immunotherapy, especially therapy based on natural killer (NK) cells, presents a promising avenue for the treatment of PDAC.AimsThis research endeavor seeks to formulate a predictive tool specifically designed for PDAC based on NK cell-related long non-coding RNA (lncRNA), revealing new molecular subtypes of PDAC to promote personalized and precision treatment.MethodsUtilizing the Tumor Immune Single-cell Hub 2 platform, we discovered genes associated with NK cells in PDAC. We employed the TCGA-PAAD dataset to ascertain the expression profiles of these NK cell-related genes and to screen for lncRNAs correlated with NK cells. Subsequently, we utilized Cox regression analysis for hazard ratios and LASSO regression analysis to identify three NK cell-related lncRNAs that were used to develop a prognostic assessment model. The forecasting accuracy of this model was appraised using the ROC curve and validated using a test set and the complete dataset.ResultsSuccessful construction of a prognostic model comprising three lncRNAs was achieved, demonstrating good predictive efficiency in the training set, validation dataset, and the entire dataset. NK cells display robust interactions with malignant cells, CD8 T cells, and fibroblasts in the PDAC tumor microenvironment and participate in the transport of various signaling molecules and following immune responses in PDAC. According to the expression patterns of NK cell-related lncRNA, we labeled PDAC patients as four molecular subtypes, exhibiting significant differences in immune cell infiltration, drug sensitivity, and other aspects.ConclusionThis study Uncovered the activity of NK cells within PDAC, proposed an NK cell-related lncRNA model, and delineated new molecular subtypes, thereby providing targets for personalized therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514259/fulltumor immune single-cell hub 2pancreatic ductal adenocarcinomaNK cell-related lncRNAstumor immune microenvironmentmolecular subtyping
spellingShingle Jinze Li
Chuqi Xia
Yuxuan Li
Hanhan Liu
Cheng Gong
Daoming Liang
Effects of NK cell-related lncRNA on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinoma
Frontiers in Immunology
tumor immune single-cell hub 2
pancreatic ductal adenocarcinoma
NK cell-related lncRNAs
tumor immune microenvironment
molecular subtyping
title Effects of NK cell-related lncRNA on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinoma
title_full Effects of NK cell-related lncRNA on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinoma
title_fullStr Effects of NK cell-related lncRNA on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinoma
title_full_unstemmed Effects of NK cell-related lncRNA on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinoma
title_short Effects of NK cell-related lncRNA on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinoma
title_sort effects of nk cell related lncrna on the immune microenvironment and molecular subtyping for pancreatic ductal adenocarcinoma
topic tumor immune single-cell hub 2
pancreatic ductal adenocarcinoma
NK cell-related lncRNAs
tumor immune microenvironment
molecular subtyping
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514259/full
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