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

Authors
 Kyung Hwan Kim  ;  Jee Suk Chang  ;  Hwa Kyung Byun  ;  Yong Bae Kim 
Citation
 JOURNAL OF GYNECOLOGIC ONCOLOGY, Vol.33(1) : e7, 2022-01 
Journal Title
JOURNAL OF GYNECOLOGIC ONCOLOGY
ISSN
 2005-0380 
Issue Date
2022-01
MeSH
Chemoradiotherapy ; Female ; Humans ; Treatment Outcome ; Uterine Cervical Neoplasms* / drug therapy ; Uterine Cervical Neoplasms* / therapy
Keywords
Cancer-associated Fibroblasts ; Cervical Cancer ; Chemoradiotherapy ; Gene Signature
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.
Files in This Item:
T202200252.pdf Download
DOI
10.3802/jgo.2022.33.e7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Kim, Yong Bae(김용배) ORCID logo https://orcid.org/0000-0001-7573-6862
Byun, Hwa Kyung(변화경) ORCID logo https://orcid.org/0000-0002-8964-6275
Chang, Jee Suk(장지석) ORCID logo https://orcid.org/0000-0001-7685-3382
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187909
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