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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Increased prognostic value of clinical–reproductive model in Chinese female patients with esophageal squamous cell carcinoma
Dong-Yun Zhang, Jian-Wei Ku, Xue-Ke Zhao, Hai-Yan Zhang, Xin Song, Hong-Fang Wu, Zong-Min Fan, Rui-Hua Xu, Duo You, Ran Wang, Ruo-Xi Zhou, Li-Dong Wang
Dong-Yun Zhang, Xue-Ke Zhao, Xin Song, Zong-Min Fan, Rui-Hua Xu, Duo You, Ran Wang, Li-Dong Wang, State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
Dong-Yun Zhang, Hong-Fang Wu, Department of Pathology, Nanyang Medical College, Nanyang 473061, Henan Province, China
Jian-Wei Ku, Department of Endoscopy, The Third Affiliated Hospital, Nanyang Medical College, Nanyang 473061, Henan Province, China
Hai-Yan Zhang, Department of Pathology, The First Affiliated Hospital, Nanyang Medical College, Nanyang 473061, Henan Province, China
Duo You, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450052, Henan Province, China
Ruo-Xi Zhou, Department of Biology, University of Richmond, Richmond, VA 23173, United States
Author contributions: Wang LD and Zhang DY designed and wrote the paper; Ku JW, Xu RH, Wang R, Wu HF, and Fan ZM performed the data collection, interpretation and follow-up; Zhang DY, Zhao XK, Zhou RX, and Song X contributed to the data analysis; all authors performed the final approvlement.
Supported by National Natural Science Foundation of China, No. 81872032 and No. U1804262; National Key R&D Program of China, No. 2016YFC0901403; High-Tech Key Projects of High School of Henan Province, No. 20B320011; and High-Tech Key Projects of Science and Technology of Henan Province Government, No. 202102310366.
Institutional review board statement: This research content and process of the project followed the international and national ethical requirements for biomedical research and agreed to publish. The study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University and Institutional Review Board of the First Affiliated Hospital of Nanyang Medical College.
Conflict-of-interest statement: We have no potential conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Li-Dong Wang, MD, PhD, Professor, State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, No. 40 Daxue Road, Zhengzhou 450052, Henan Province, China. ldwangpaper2018@126.com
Received: October 25, 2021
Peer-review started: October 25, 2021
First decision: January 9, 2022
Revised: January 21, 2022
Accepted: February 27, 2022
Article in press: February 27, 2022
Published online: April 7, 2022
BACKGROUND
In China, it has been well recognized that some female patients with esophageal squamous cell carcinoma (ESCC) have different overall survival (OS) time, even with the same tumor-node-metastasis (TNM) stage, challenging the prognostic value of the TNM system alone. An effective predictive model is needed to accurately evaluate the prognosis of female ESCC patients.
AIM
To construct a novel prognostic model with clinical and reproductive data for Chinese female patients with ESCC, and to assess the incremental prognostic value of the full model compared with the clinical model and TNM stage.
METHODS
A new prognostic nomogram incorporating clinical and reproductive features was constructed based on univariatie and Cox proportional hazards survival analysis from a training cohort (n = 175). The results were recognized using the internal (n = 111) and independent external (n = 85) validation cohorts. The capability of the clinical–reproductive model was evaluated by Harrell’s concordance index (C-index), Kaplan–Meier curve, time-dependent receiver operating characteristic (ROC), calibration curve and decision curve analysis. The correlations between estrogen response and immune-related pathways and some gene markers of immune cells were analyzed using the TIMER 2.0 database.
RESULTS
A clinical–reproductive model including incidence area, age, tumor differentiation, lymph node metastasis (N) stage, estrogen receptor alpha (ESR1) and beta (ESR2) expression, menopausal age, and pregnancy number was constructed to predict OS in female ESCC patients. Compared to the clinical model and TNM stage, the time-dependent ROC and C-index of the clinical–reproductive model showed a good discriminative ability for predicting 1-, 3-, and 5-years OS in the primary training, internal and external validation sets. Based on the optimal cut-off value of total prognostic scores, patients were classified into high- and low-risk groups with significantly different OS. The estrogen response was significantly associated with p53 and apoptosis pathways in esophageal cancer.
CONCLUSION
The clinical–reproductive prognostic nomogram has an incremental prognostic value compared with the clinical model and TNM stage in predicting OS in Chinese female ESCC patients.
Core Tip: In China, some female patients with esophageal squamous cell carcinoma (ESCC), even with the same tumor-node-metastasis (TNM) stage, have significantly different overall survival (OS) time. The prognostic value of the TNM system has been challenged due to its unsatisfactory discriminative ability. A new prognostic nomogram that combines clinical and reproductive features was developed and validated in this study. Compared with the clinical model and TNM stage, clinical–reproductive model has incremental prognostic value in predicting OS in Chinese female patients with ESCC, which can help clinicians to make individual treatment and medical decisions.
