Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related mortality worldwide. Immunotherapy offers promising new treatment options for gastric cancer patients; however, it is only effective in a limited fraction of patients. In this study, we evaluated the com...

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Main Authors: Weiqiang Yu, Shuaili Wang, Qiqi Rong, Olugbenga Emmanuel Ajayi, Kongwang Hu, Qingfa Wu
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/13/6/1017
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author Weiqiang Yu
Shuaili Wang
Qiqi Rong
Olugbenga Emmanuel Ajayi
Kongwang Hu
Qingfa Wu
author_facet Weiqiang Yu
Shuaili Wang
Qiqi Rong
Olugbenga Emmanuel Ajayi
Kongwang Hu
Qingfa Wu
author_sort Weiqiang Yu
collection DOAJ
description Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related mortality worldwide. Immunotherapy offers promising new treatment options for gastric cancer patients; however, it is only effective in a limited fraction of patients. In this study, we evaluated the composition of 22 tumor-infiltrating lymphocytes (TILs) in TCGA Stomach Adenocarcinoma (STAD) using deconvolution-based method by analyzing the publicly available bulk tumor RNA-seq data. The patients were classified into high-TIL and low-TIL subtypes based on their immune cell profiles and prognosis outputs. The differentially expressed genes (DEGs) between the two subtypes were identified, and GO/KEGG analysis showed that broad immune genes, such as PD-L1 and PD-1, were highly expressed in the high-TIL subtype. A comprehensive protein–protein interaction (PPI) network centered on DEGs was built, and 16 hub genes of the network were further identified. Based on the hub genes, an elastic model with 11 gene signatures (<i>NKG7</i>, <i>GZMB</i>, <i>IL2RB</i>, <i>CCL5</i>, <i>CD8A</i>, <i>IDO1</i>, <i>MYH1</i>, <i>GNLY</i>, <i>CXCL11</i>, <i>GBP5</i> and <i>PRF1</i>) was developed to predict the high-TIL subtype. In summary, our findings showed that the compositions of TILs within the tumor immune microenvironment of stomach cancer patients are highly heterogeneous, and the profiles of TILs have the potential to be predictive markers of patients’ responses and overall survival outcomes.
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spelling doaj.art-e749176f97ba4e299e6099d6d14a12132023-11-23T16:47:55ZengMDPI AGGenes2073-44252022-06-01136101710.3390/genes13061017Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the PrognosisWeiqiang Yu0Shuaili Wang1Qiqi Rong2Olugbenga Emmanuel Ajayi3Kongwang Hu4Qingfa Wu5Division of Molecular Medicine, CAS Key Laboratory of Innate Immunity and Chronic Disease, Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDivision of Molecular Medicine, CAS Key Laboratory of Innate Immunity and Chronic Disease, Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDivision of Molecular Medicine, CAS Key Laboratory of Innate Immunity and Chronic Disease, Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDivision of Molecular Medicine, CAS Key Laboratory of Innate Immunity and Chronic Disease, Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of General Surgery, Fuyang Hospital Affiliated to Anhui Medical University, Fuyang 236000, ChinaDivision of Molecular Medicine, CAS Key Laboratory of Innate Immunity and Chronic Disease, Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaGastric cancer is the fifth most common malignancy and the third leading cause of cancer-related mortality worldwide. Immunotherapy offers promising new treatment options for gastric cancer patients; however, it is only effective in a limited fraction of patients. In this study, we evaluated the composition of 22 tumor-infiltrating lymphocytes (TILs) in TCGA Stomach Adenocarcinoma (STAD) using deconvolution-based method by analyzing the publicly available bulk tumor RNA-seq data. The patients were classified into high-TIL and low-TIL subtypes based on their immune cell profiles and prognosis outputs. The differentially expressed genes (DEGs) between the two subtypes were identified, and GO/KEGG analysis showed that broad immune genes, such as PD-L1 and PD-1, were highly expressed in the high-TIL subtype. A comprehensive protein–protein interaction (PPI) network centered on DEGs was built, and 16 hub genes of the network were further identified. Based on the hub genes, an elastic model with 11 gene signatures (<i>NKG7</i>, <i>GZMB</i>, <i>IL2RB</i>, <i>CCL5</i>, <i>CD8A</i>, <i>IDO1</i>, <i>MYH1</i>, <i>GNLY</i>, <i>CXCL11</i>, <i>GBP5</i> and <i>PRF1</i>) was developed to predict the high-TIL subtype. In summary, our findings showed that the compositions of TILs within the tumor immune microenvironment of stomach cancer patients are highly heterogeneous, and the profiles of TILs have the potential to be predictive markers of patients’ responses and overall survival outcomes.https://www.mdpi.com/2073-4425/13/6/1017gastric cancerimmunotherapytumor-infiltrating lymphocyteshub-genesprognosis
spellingShingle Weiqiang Yu
Shuaili Wang
Qiqi Rong
Olugbenga Emmanuel Ajayi
Kongwang Hu
Qingfa Wu
Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis
Genes
gastric cancer
immunotherapy
tumor-infiltrating lymphocytes
hub-genes
prognosis
title Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis
title_full Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis
title_fullStr Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis
title_full_unstemmed Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis
title_short Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis
title_sort profiling the tumor infiltrating lymphocytes in gastric cancer reveals its implication in the prognosis
topic gastric cancer
immunotherapy
tumor-infiltrating lymphocytes
hub-genes
prognosis
url https://www.mdpi.com/2073-4425/13/6/1017
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