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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Identification and Characterization of Metabolic Subtypes of Endometrial Cancer Using a Systems-Level Approach.

Akansha Srivastava¹, Palakkad Krishnanunni Vinod¹

¹Centre for Computational Natural Sciences and Bioinformatics, IIIT, Hyderabad 500032, India.

|March 29, 2023

Summary

Endometrial cancer (EC) exhibits metabolic heterogeneity. Two distinct metabolic subtypes were identified, correlating with patient survival, tumor stage, and genomic alterations, offering new diagnostic and therapeutic insights.

Keywords:

endometrial cancer metabolic reprogramming reporter metabolites systems biology transcriptome

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Area of Science:

Oncology
Metabolomics
Genomics

Background:

Endometrial cancer (EC) is the most prevalent gynecological malignancy globally.
Understanding tumor metabolic adaptation and heterogeneity is crucial for advancing EC diagnosis, prognosis, and treatment strategies.

Purpose of the Study:

To investigate metabolic alterations and identify distinct metabolic subtypes within endometrial cancer tissues.
To uncover dysregulated metabolic pathways and reporter metabolites associated with these subtypes.
To explore the relationship between metabolic subtypes, clinical variables, and genomic alterations.

Main Methods:

Integration of endometrial cancer transcriptomics (RNA-Seq) data with a human genome-scale metabolic network.
Identification of metabolic subtypes based on metabolic profiles.
Correlation analysis between metabolic subtypes and clinical data (survival, tumor stage).
Analysis of genomic alterations (mutations, copy number variations) in relation to metabolic subtypes.

Main Results:

Endometrial cancer patients were stratified into two metabolic subtypes (subtype-1 and subtype-2).
Metabolic subtypes showed significant correlations with patient survival, tumor stages, and genomic variations.
Metabolic subtype-2 exhibited co-activation of the pentose phosphate pathway, one-carbon metabolism, and estrogen-regulating genes, linked to poorer survival.
Upregulation of PNMT and ERBB2, along with amplification at chromosome locus 17q12, was observed in subtype-2.
Mutually exclusive PTEN and TP53 mutations were associated with differential survival between subtypes.

Conclusions:

This study successfully identified distinct metabolic subtypes in endometrial cancer based on transcriptomic and genomic profiles.
Metabolic heterogeneity within EC is characterized by distinct molecular features and clinical outcomes.
The identified metabolic subtypes provide potential targets for novel diagnostic and therapeutic approaches in endometrial cancer management.