Research Paper Volume 16, Issue 1 pp 568—592
Immune landscape and heterogeneity of cervical squamous cell carcinoma and adenocarcinoma
- 1 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China
- 2 Department of Gynecologic Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
- 3 Cancer Biology Research Center (Key Laboratory of The Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430100, Hubei, China
- 4 Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
- 5 BGI-Shenzhen, Shenzhen 518083, Guangzhou, China
- 6 Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang, China
Received: July 12, 2023 Accepted: October 17, 2023 Published: January 10, 2024
https://doi.org/10.18632/aging.205397How to Cite
Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Despite the differences in disease outcomes and pathological features between cervical squamous cell carcinoma (CSCC) and adenocarcinoma (ADC), the molecular characteristics in immune heterogeneity of the tumor microenvironment remain unclear. Here, we explored the immune landscape and heterogeneity between CSCC and ADC. Gene expression and clinical characteristics of cervical carcinoma from The Cancer Genome Atlas (TCGA) were downloaded. Differentially expressed genes (DEGs), immune cell infiltration, and pathway enrichment analyses were used to explore the immune landscape and heterogeneity between CSCC and ADC. Furthermore, distinct immune signatures between CSCC and ADC were validated based on clinical samples. In total, 4,132 upregulated DEGs and 2,307 down-regulated DEGs were identified between CSCC and ADC, with enrichments in immune related-pathways in CSCC. In addition, 54 hub DEGs correlated with patients’ prognosis and immunocytes infiltration were identified. The CSCC patients had a higher ImmuneScore and more abundant immunocytes infiltration compared to ADC patients, as validated by immunohistochemistry (IHC) and multicolor immunofluorescence (mIF) analyses of collected samples. Furthermore, CSCC displayed higher inhibitory immune checkpoints expression, tumor mutation burden (TMB), and microsatellite instability (MSI) compared to ADC, which indicated CSCC patients were more likely to benefit from immunotherapy. In summary, our results revealed the huge immune heterogeneity between CSCC and ADC, and provided guidance for immunotherapy selection for different pathological types of cervical cancer.
Abbreviations
GSVA: Gene Set Variation Analysis; CSCC: squamous cell carcinoma; ADC: adenocarcinoma; HPV: human papillomavirus; DEGs: differentially expressed genes; IRGs: immune related genes; HR: hazard ratio; MSI: microsatellite instability; TMB: tumor mutation burden; IHC: immunohistochemistry; mIF: multicolor immunofluorescence; TCGA: The Cancer Genome Atlas; FDR: false discovery rate; PCA: principal component analysis; IRGs: immune related genes; MHC: major histocompatibility complex; OS: overall survival; ROC: receiver operating characteristic.