Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy

• Main Authors: Ying-Chun Lin, Yu-Chia Chen, Rui-Yun Chen, Yi-Xuan Huang, Siang-Jyun Tu, Ji-An Liang, Yao-Ching Hung, Lian-Shung Yeh, Wei-Chun Chang, Wu-Chou Lin, Yin-Yi Chang, Shang-Wen Chen, Jan-Gowth Chang
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: International Journal of Molecular Sciences
• Subjects: cervical adenocarcinoma; chemoradiotherapy; genomic alteration; next-generation sequencing; myeloid cell leukemia-1
• Online Access: https://www.mdpi.com/1422-0067/21/11/4117

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (<i>MCL1</i>) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (<i>p</i> = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by <i>MCL1</i> amplification, the TMN, and the TNF-α H score.