A novel gene signature associated with poor response to chemoradiotherapy in patients with locally advanced cervical cancer

Kyung Hwan Kim, Jee Suk Chang, Hwa Kyung Byun, Yong Bae Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: We aimed to investigate the distinct transcriptional landscape in poor responders to concurrent chemoradiotherapy (CCRT) and to gain mechanistic insights into treatment resistance in cervical cancer. Methods: RNA sequencing was performed in patients with locally advanced cervical cancer treated with platinum-based CCRT. Transcriptome data of no durable benefit (NDB; progression-free period <3 years) and durable clinical benefit (DCB; progression-free period >5 years) patients were compared. The NDB score was estimated for each patient using differentially expressed genes between NDB and DCB patients. The potential response to programmed death-1 blockade was estimated using the tumor immune dysfunction and exclusion (TIDE) score and T-cell-inflamed gene expression profile (GEP). Results: NDB patients exhibited a distinct transcriptional profile compared to DCB patients, such as higher signatures of extracellular matrix organization and epithelial-to-mesenchymal transition. The fraction of cancer-associated fibroblasts (CAFs) within the tumor was significantly higher in NDB patients than in DCB patients. High NDB scores were significantly associated with poor survival in the Cancer Genome Atlas cervical cancer cohort (n=274; p=0.015) but only in patients who received curative aim radiotherapy (p=0.002). Patients with high NDB scores displayed significantly higher TIDE prediction scores and lower T-cell-inflamed GEP scores than those with low NDB scores. Conclusion: Patients with cervical cancer having poor CCRT or RT outcomes exhibited a distinct gene signature that could predict treatment outcomes. For poor responders, immune checkpoint inhibitors may be less effective whereas CAF-targeting treatments may be a promising approach.

Original languageEnglish
Article numbere7
JournalJournal of Gynecologic Oncology
Volume33
Issue number1
DOIs
Publication statusPublished - 2022 Jan

Bibliographical note

Funding Information:
This study was supported by a faculty research grant of Yonsei University College of Medicine (6-2021-0098).

Publisher Copyright:
© 2022, Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynaecology

Fingerprint

Dive into the research topics of 'A novel gene signature associated with poor response to chemoradiotherapy in patients with locally advanced cervical cancer'. Together they form a unique fingerprint.

Cite this