Preoperative Serum CA125, CEA, and AFP as Prognostic Biomarkers for Endometrial Cancer Patients

Core Concepts

Elevated preoperative serum levels of CA125, CEA, and AFP are independent prognostic factors for poor progression-free survival and overall survival in endometrial cancer patients.

Abstract

This retrospective study analyzed data from 2,081 endometrial cancer patients to investigate the prognostic significance of preoperative serum levels of CA125, CA19-9, CA72-4, CEA, and AFP.
Key highlights:

Elevated preoperative serum levels of CA125, CEA, and AFP were identified as independent prognostic factors for poor progression-free survival (PFS) and overall survival (OS) in endometrial cancer patients.
Patients with high levels of CA125 (>35 U/mL), CEA (>5 ng/mL), and AFP (>9 ng/mL) had significantly worse PFS and OS compared to those with normal levels.
A risk score combining the levels of CA125, CEA, and AFP was developed and validated, which was an independent predictor of PFS and OS.
Nomograms incorporating the risk score, FIGO stage, age, and tumor grade showed good discriminative ability and calibration for predicting 3- and 5-year PFS and OS.
The study suggests that preoperative serum CA125, CEA, and AFP levels can be used as prognostic biomarkers to identify high-risk endometrial cancer patients and guide personalized treatment strategies.

Stats

Patients with elevated preoperative serum CA125 (P<0.0001), CEA (P<0.0001), and AFP (P<0.0001) levels had significantly worse progression-free survival compared to those with normal levels.
Patients with elevated preoperative serum CA125 (P=0.003), CEA (P=0.014), and AFP (P<0.0001) levels had significantly worse overall survival compared to those with normal levels.

Quotes

"Elevated serum CA125 (P < 0.001) and AFP (P < 0.001), CEA (P = 0.037), age (P = 0.023), menopausal status (P = 0.034), pathological type (P = 0.004), degree of differentiation (P = 0.001), FIGO stage (P < 0.001), and lymphovascular infiltrates (P < 0.001) were independent factors for PFS prognosis in EC patients."
"Increased serum CA125 (P = 0.003), AFP (P < 0.001), CEA (P = 0.014), age (P = 0.004), pathological type (P = 0.005), degree of differentiation (P = 0.015), FIGO stage (P < 0.001), and lymphovascular infiltrates (P = 0.003) were independent factors for prognosis of OS in EC patients."

Key Insights Distilled From

Prognostic Significance of preoperative serum CA125, CA19-9, CA72-4, CEA, and AFP in Patients with Endometrial cancer

by Wang,Z.-h., ... at www.biorxiv.org 01-26-2024

https://www.biorxiv.org/content/10.1101/2024.01.23.576857v1

Deeper Inquiries

What are the potential mechanisms by which elevated serum CA125, CEA, and AFP levels contribute to poor prognosis in endometrial cancer patients

Elevated serum levels of CA125, CEA, and AFP in endometrial cancer patients can contribute to a poor prognosis through various potential mechanisms:

CA125:

CA125 is a glycoprotein that is overexpressed in many cancers, including endometrial cancer. Elevated CA125 levels can indicate a larger tumor burden, increased tumor invasiveness, and a higher likelihood of metastasis.
CA125 is associated with tumor growth, angiogenesis, and immune evasion, all of which can contribute to disease progression and poor prognosis in endometrial cancer patients.

CEA:

Carcinoembryonic antigen (CEA) is a glycoprotein that is often elevated in various cancers, including endometrial cancer. High CEA levels can indicate more aggressive tumor behavior and a higher risk of metastasis.
CEA is involved in cell adhesion, invasion, and metastasis, promoting tumor progression and potentially leading to a poorer prognosis in endometrial cancer patients.

AFP:

Alpha-fetoprotein (AFP) is a fetal protein that is typically produced by the liver and yolk sac during fetal development. Elevated AFP levels in endometrial cancer patients can indicate a more aggressive subtype of the disease.
AFP-producing endometrial carcinomas are associated with TP53 abnormalities, vascular invasion, and aggressive behavior, leading to a poorer prognosis compared to other endometrial cancer subtypes.

In summary, the elevated levels of CA125, CEA, and AFP in endometrial cancer patients may reflect increased tumor burden, invasiveness, aggressiveness, and metastatic potential, all of which contribute to a poor prognosis.

How can the risk score incorporating these biomarkers be further optimized and validated in larger, more diverse patient populations

To further optimize and validate the risk score incorporating CA125, CEA, and AFP in endometrial cancer patients, the following steps can be taken:

Optimization:

Include additional relevant biomarkers or clinical parameters that may enhance the predictive power of the risk score.
Refine the weighting of each biomarker in the risk score based on larger datasets and more diverse patient populations.
Consider incorporating dynamic changes in biomarker levels over time to improve the accuracy of the risk score.

Validation:

Validate the risk score in larger, multicenter cohorts to ensure its generalizability and reliability across different patient populations.
Conduct external validation studies to confirm the predictive performance of the risk score in independent cohorts.
Perform sensitivity analyses to assess the robustness of the risk score across different subgroups of endometrial cancer patients.

By optimizing and validating the risk score incorporating CA125, CEA, and AFP in larger and more diverse patient populations, clinicians can have a more accurate and reliable tool for predicting the prognosis of endometrial cancer patients.

Could the combination of these serum biomarkers with other emerging molecular or imaging biomarkers provide even more accurate prognostic prediction for endometrial cancer

Combining serum biomarkers such as CA125, CEA, and AFP with other emerging molecular or imaging biomarkers has the potential to provide even more accurate prognostic prediction for endometrial cancer. Some strategies to enhance prognostic prediction include:

Incorporating Molecular Biomarkers:

Include molecular biomarkers such as genetic mutations, gene expression profiles, or epigenetic alterations that can provide additional insights into tumor biology and behavior.
Molecular biomarkers related to specific pathways or molecular subtypes of endometrial cancer can offer personalized prognostic information and guide targeted treatment strategies.

Integrating Imaging Biomarkers:

Combine serum biomarkers with imaging techniques such as MRI, PET-CT, or ultrasound to assess tumor characteristics, staging, and response to treatment.
Radiomics, which involves extracting quantitative features from medical images, can be integrated with serum biomarkers to improve prognostic accuracy and treatment planning.

Machine Learning Approaches:

Utilize machine learning algorithms to integrate multiple biomarkers and clinical data for more sophisticated prognostic models.
Ensemble methods, deep learning, and other advanced machine learning techniques can optimize the predictive power of combined biomarkers for endometrial cancer prognosis.

By combining serum biomarkers with other emerging molecular or imaging biomarkers and leveraging advanced analytical approaches, clinicians can enhance the accuracy and precision of prognostic prediction for endometrial cancer patients, leading to more personalized and effective treatment strategies.