# Molecular classification and prognosis study of pancreatic ductal adenocarcinoma through multi-omics integrated clustering analysis

## TL;DR

This study identifies two distinct subtypes of pancreatic cancer using multi-omics data and finds that one subtype is more aggressive and less responsive to immune activity.

## Contribution

A novel multi-omics clustering approach identifies two PDAC subtypes with distinct prognostic and therapeutic implications.

## Key findings

- Two PDAC subtypes (CS1 and CS2) were identified with differing survival rates and immune characteristics.
- CS1 subtype is high-risk, immunosilent, and more chemotherapy-sensitive compared to CS2.
- The IL20RB gene shows strong predictive power and potential as a therapeutic target.

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by significant heterogeneity. We conducted a multi-omics integrated clustering analysis to categorize PDAC molecular subtypes.

Multi-omics data from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) were integrated using ten clustering algorithms. Comparisons across PDAC subtypes were performed regarding prognosis, gene mutations, pathways, tumor microenvironment (TME), and chemotherapy sensitivity. A prognostic model was constructed utilizing Cox and Lasso regression based on subtype-related genes.

Samples from the TCGA-PAAD cohort were classified into two subtypes. The CS1 subtype was identified as a high-risk, immunosilent subtype, while the CS2 subtype was characterized as a low-risk, immunoactive subtype. Compared to CS2 subtype, CS1 subtype exhibited shorter survival, higher frequency of genetic mutations, more aggressive tumor-promoting nature, lower TME immune score, and increased sensitivity to chemotherapy. The prognostic model related to PDAC subtypes displayed robust predictive efficiency; IL20RB gene emerged having superior predictive capability.

We successfully identified two distinct PDAC subtypes. The developed prognostic model exhibited strong predictive efficacy; and the upregulation of IL20RB was identified as a promising therapeutic target for PDAC.