Tumor Molecular Features Predict Endometrial Cancer Patients' Survival After Open or Minimally Invasive Surgeries

Abstract

Background: The Cancer Genome Atlas (TCGA) project shed light on the vital role of tumor molecular features in predicting endometrial cancer patients' prognosis. This study aims to investigate the survival impact of surgical approaches on patients with different genetic alterations.

Methods: 473 endometrial cancer patients from TCGA database were selected. To analyze the prognostic impact of surgical approach, survival analyses were conducted in patients with different molecular features. Finally, a simplified molecular stratification model was established to select patients suitable for open or minimally invasive surgery (MIS).

Results: In our cohort, 291 patients received open surgery and 182 received MIS. Molecular features influenced patients' survival after different surgical approaches. Based on survival analyses, three molecular subtypes were generated, with subtype 1 harboring POLE mutation (POLE^mt ), microsatellite-instability high (MSI-H), homologous recombination repair (HRR) pathway mutation or MUC16 mutation (MUC16^mt ); subtype 3 carrying TP53 mutation; and subtype 2 without specific molecular feature. The survival influence of molecular subtypes depended on surgical approaches. In the open surgery cohort, three subtypes showed similar survival outcome, while in the MIS cohort, prognosis varied significantly among three subtypes, with subtype 1 the best and subtype 3 the worst. In stepwise Cox regression, molecular subtype was an independent predictor of recurrence-free survival in patients receiving MIS (p < 0.001).

Conclusion: The molecular features of endometrial cancer are associated with patients' prognosis after different surgical approaches. MIS should be recommended in patients with POLE^mt , MSI-H, HRR pathway mutation or MUC16^mt , while for patients with TP53 mutation, open surgery is better concerning oncological safety.

Keywords: endometrial neoplasms; minimally invasive surgical procedures; molecular features; recurrence; survival.

Figure 1

Kaplan-Meier survival curves of patients with different genetic features by surgical approach. (A) Recurrence-free survival of patients with POLE^wt. (B) Recurrence-free survival of non MSI-H patients. (C) Recurrence-free survival of HRR with wild type patients. (D) Recurrence-free survival of patients with MUC16^wt. (E) Recurrence-free survival of patients with CTNBB1^wt. (F) Recurrence-free survival of patients with TP53^wt. MIS, minimally invasive surgery; POLE^wt, POLE wild type; MSI-H, microsatellite-instability high; HRR, homologous recombination repair; MUC16^wt, MUC16 wild type; CTNNB1^wt, CTNNB1 wild type; TP53^mt, TP53 mutation.

Figure 2

The survival influence of surgical approach in different TCGA molecular subgroups. (A) The distribution of 4 TCGA molecular subtypes in the cohort. (B) Genetic alterations in each molecular subtype. (C–F) Kaplan-Meier survival curves of patients with different molecular features by surgical approach. TCGA, the Cancer Genome Atlas; POLE^mt, POLE mutation; MSI-H, microsatellite-instability high; HRR, homologous recombination repair; MUC16^mt, MUC16 mutation; CTNNB1^mt, CTNNB1 mutation; CTNNB1^wt, CTNNB1 wild type; TP53^mt, TP53 mutation; TP53^wt, TP53 wild type; MIS, minimally invasive surgery.

Figure 3

Survival of patients by simplified molecular subtypes. (A, B) Kaplan-Meier survival curves of all patients by three molecular subtypes. (C, D) Kaplan-Meier survival curves of the open surgery cohort by three molecular subtypes. (E, F) Kaplan-Meier survival curves of the MIS cohort by three molecular subtypes. MIS, minimally invasive surgery.

Figure 4

Hypothetical schemas for choosing surgical approaches based on patients’ molecular features. (A) A TCGA-based model for deciding proper surgical approach. (B) A simplified model for deciding proper surgical approach. TCGA, the Cancer Genome Atlas; MSI, microsatellite-instability; CTNNB1^mt, CTNNB1 mutation; CTNNB1^wt, CTNNB1 wild type; TP53^mt, TP53 mutation; TP53^wt, TP53 wild type; MIS, minimally invasive surgery; POLE^mt, POLE mutation; MSI-H, microsatellite-instability high; HRR, homologous recombination repair; MUC16^mt, MUC16 mutation; TMB, tumor mutation burden. ^a Patients with concurrent TP53^mt and CTNNB1^mt are excluded and should be separately discussed.