The differences in immune features and genomic profiling between squamous cell carcinoma and adenocarcinoma - A multi-center study in Chinese patients with uterine cervical cancer

Jin Li; Xiaohong Xue; Yan Zhang; Fengna Ding; Wenyan Wu; Cuicui Liu; Yang Xu; Hanlin Chen; Qiuxiang Ou; Yang Shao; Xinjun Li; Fei Wu; Xiaohua Wu

doi:10.1016/j.ygyno.2023.05.071

The differences in immune features and genomic profiling between squamous cell carcinoma and adenocarcinoma - A multi-center study in Chinese patients with uterine cervical cancer

Gynecol Oncol. 2023 Aug:175:133-141. doi: 10.1016/j.ygyno.2023.05.071. Epub 2023 Jun 23.

Authors

Jin Li¹, Xiaohong Xue², Yan Zhang³, Fengna Ding⁴, Wenyan Wu⁵, Cuicui Liu⁶, Yang Xu⁶, Hanlin Chen⁶, Qiuxiang Ou⁶, Yang Shao⁷, Xinjun Li⁸, Fei Wu⁹, Xiaohua Wu¹⁰

Affiliations

¹ Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² Department of Gynecology, Obstetrics & Gynecology, Hospital of Fudan University, Fudan University, Shanghai, China.
³ Department of Gynecology, Weifang People's Hospital, Shandong, China.
⁴ Department of Gynecologic Oncology, Shandong Linyi Tumor Hospital, Shandong, China.
⁵ Department of Obstetrics and Gynecology, Longyan First Affiliated Hospital of Fujian Medical University, Fujian, China.
⁶ Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
⁷ Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China; School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
⁸ Department of Gynecology, Hebei General Hospital, Hebei, China.
⁹ Department of Gynecology, Maternal and Child Health Hospital of Hunan Province, Hunan, China.
¹⁰ Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: wu.xh@fudan.edu.cn.

PMID: 37356314
DOI: 10.1016/j.ygyno.2023.05.071

Abstract

Background: Squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix have distinct biological behaviors and different treatment responses. Studies on immune features and genomic profiling of these two pathologic types were limited and mainly focused on small patient cohorts.

Methods: From 2014 to 2021, 336 (254 SCC vs. 82 AC) cervical cancer patients who were diagnosed/treated in 7 medical centers in China were enrolled in the study. Next-generation sequencing of 425 cancer-relevant genes was performed on tumor tissues and liquid biopsies. Somatic alterations and immune response-related biomarkers were analyzed. Patient prognosis and immune infiltration were analyzed using data from The Cancer Genome Atlas (TCGA).

Results: AC tended to have more immunotherapy resistance-related STK11 alterations (P = 0.039), a higher proportion of microsatellite instability (P = 0.21), and more actionable mutations (P = 0.161). In contrast, higher tumor mutational burdens (TMB; P = 0.01), a higher proportion of TMB-high patients (P = 0.016), and more PD-L1-high patients (P = 0.0013) were observed in SCC. Multiple genetic alterations and aberrant signaling pathways were specifically enriched in AC (e.g., TP53, KRAS, ERBB2, and ARID1A alterations) or SCC (e.g., PIK3CA, FBXW7, EP300, and BAP1 mutations). Notably, AC-enriched genetic changes were significantly associated with decreased infiltrations of various B cells, T cells, and dendritic cells, whereas SCC-associated molecular features tended to be associated with increased CD4+ T cell infiltrations.

Conclusions: This was the first multi-center study revealing the immunologic and genomic features between SCC and AC in Chinese patients with cervical cancer. Our findings have illustrated the difference in genetic profiles of those two cervical cancer subtypes, which may suggest the possibility of differential treatment regimens, with better immunotherapy efficacy in SCC and targeted therapy options more favorable in AC.

Keywords: Adenocarcinoma; Cervical cancer; Genomic profiles; Immune features; Squamous cell carcinoma.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / genetics
Adenocarcinoma* / immunology
Adenocarcinoma* / pathology
Biomarkers
Carcinoma, Squamous Cell* / genetics
Carcinoma, Squamous Cell* / immunology
Carcinoma, Squamous Cell* / pathology
East Asian People
Female
Genetic Profile
Humans
Mutation
Uterine Cervical Neoplasms* / genetics
Uterine Cervical Neoplasms* / immunology
Uterine Cervical Neoplasms* / pathology

Substances

Biomarkers