Increased Prognostic Value of Clinical-reproductive Model in Chinese Female Patients with Esophageal Squamous Cell Carcinoma

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 ( = 175). The results were recognized using the internal ( = 111) and independent external ( = 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.