Xiao-Jing Qin1, Xu Lin1, Gang Xue2, Hui-Li Fan1, Hao-Yu Wang1, Jing-Fang Wu1, Da Pei1. 1. Department of Histology and Embryology, Hebei North University, Zhangjiakou 075000, China. 2. Department of Otorhinolaryngology Head and Neck Surgery, Hebei North University, Zhangjiakou 075000, China.
Abstract
BACKGROUND: In recent years, the annual incidence of thyroid cancer (TC) has increased, with papillary thyroid cancer (PTC) identified as the most commonwinwordpathological type accounting for approximately 80% of all thyroid cancer cases. The tumor microenvironment is known to play a vital role in tumor information transmission and immune detection. METHODS: In the present study, we examined gene expression data from 518 patients with PTC. The ESTIMATE algorithm was used to calculate immune and stromal scores of PTC patients. Based on a protein-protein interaction (PPI) network, functional enrichment and overall survival analyses, C-X-C motif chemokine ligand 10 (CXCL10) was identified as a core gene. We further investigated the roles of core genes of PTC in the tumor immune microenvironment using LinkedOmics, GSEA, and TIMER tools. RESULTS: Immune, stromal and ESTIMATE scores were related to clinicopathological variables of patients with PTC, but not survival outcomes. Eight differentially expressed genes (DEGs) were associated with survival outcome. In addition, immunochemical staining experiments revealed lower expression of CXCL10 in PTC than paracancerous tissues. GSEA pathway enrichment analysis revealed downregulation of CXCL10 in multiple cancer pathways. CXCL10 and related genes were enriched in pathways related to adaptive immune response, cellular defense response and regulation of innate immune response. CONCLUSION: The tumor microenvironment plays a critical role in development of PTC and CXCL10 may serve as a novel target of precision therapy for this patient population.
BACKGROUND: In recent years, the annual incidence of thyroid cancer (TC) has increased, with papillary thyroid cancer (PTC) identified as the most commonwinwordpathological type accounting for approximately 80% of all thyroid cancer cases. The tumor microenvironment is known to play a vital role in tumor information transmission and immune detection. METHODS: In the present study, we examined gene expression data from 518 patients with PTC. The ESTIMATE algorithm was used to calculate immune and stromal scores of PTC patients. Based on a protein-protein interaction (PPI) network, functional enrichment and overall survival analyses, C-X-C motif chemokine ligand 10 (CXCL10) was identified as a core gene. We further investigated the roles of core genes of PTC in the tumor immune microenvironment using LinkedOmics, GSEA, and TIMER tools. RESULTS: Immune, stromal and ESTIMATE scores were related to clinicopathological variables of patients with PTC, but not survival outcomes. Eight differentially expressed genes (DEGs) were associated with survival outcome. In addition, immunochemical staining experiments revealed lower expression of CXCL10 in PTC than paracancerous tissues. GSEA pathway enrichment analysis revealed downregulation of CXCL10 in multiple cancer pathways. CXCL10 and related genes were enriched in pathways related to adaptive immune response, cellular defense response and regulation of innate immune response. CONCLUSION: The tumor microenvironment plays a critical role in development of PTC and CXCL10 may serve as a novel target of precision therapy for this patient population.
Authors: Gautier Koscielny; Peter An; Denise Carvalho-Silva; Jennifer A Cham; Luca Fumis; Rippa Gasparyan; Samiul Hasan; Nikiforos Karamanis; Michael Maguire; Eliseo Papa; Andrea Pierleoni; Miguel Pignatelli; Theo Platt; Francis Rowland; Priyanka Wankar; A Patrícia Bento; Tony Burdett; Antonio Fabregat; Simon Forbes; Anna Gaulton; Cristina Yenyxe Gonzalez; Henning Hermjakob; Anne Hersey; Steven Jupe; Şenay Kafkas; Maria Keays; Catherine Leroy; Francisco-Javier Lopez; Maria Paula Magarinos; James Malone; Johanna McEntyre; Alfonso Munoz-Pomer Fuentes; Claire O'Donovan; Irene Papatheodorou; Helen Parkinson; Barbara Palka; Justin Paschall; Robert Petryszak; Naruemon Pratanwanich; Sirarat Sarntivijal; Gary Saunders; Konstantinos Sidiropoulos; Thomas Smith; Zbyslaw Sondka; Oliver Stegle; Y Amy Tang; Edward Turner; Brendan Vaughan; Olga Vrousgou; Xavier Watkins; Maria-Jesus Martin; Philippe Sanseau; Jessica Vamathevan; Ewan Birney; Jeffrey Barrett; Ian Dunham Journal: Nucleic Acids Res Date: 2016-11-29 Impact factor: 16.971