Feature Selection and Network-Driven Analyses to Unveil Common RNA Signatures in Colon and Pancreatic KRAS-Mutant Cancers

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-02-27 DOI:10.1002/cam4.70468

Katia Pane, Mario Zanfardino, Anna Maria Grimaldi, Ilaria Leone, Silvia Nuzzo, Marco Salvatore, Monica Franzese

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引用次数: 0

Abstract

Background

Colon cancer and pancreatic ductal adenocarcinoma are among the most aggressive tumors for which therapeutic options are limited. Both cancers share common features, such as some KRAS pathogenic variants and common epidemiology. The integration of multidimensional datasets by combining machine learning and bioinformatics approaches could provide deeper insights into the intricate KRAS-related networks underlying cancer progression and unveil novel biomarkers and potential therapeutic targets. This study aimed to uncover colon and pancreatic cancers that shared transcriptional changes closely related to KRAS missense mutations.

Methods

Feature Selection (FS) technique and Qiagen's Ingenuity Pathway Analysis (IPA) were used to combine DNA-Seq and RNA-Seq data from mutant and wild-type (WT) KRAS colon and pancreatic tumor samples.

Results

From the FS, we prioritized 70 genes (54 protein-coding genes and 16 ncRNA-coding genes) that were able to discriminate between WT and mutated KRAS patients. These genes were involved in KRAS signaling and other related processes, such as EMT signaling, glycolysis, apical junction, Wnt/beta-catenin signaling, and IL-2/STAT5 signaling. Using IPA, we identified a top-scoring network of 19 upregulated genes in both tumor types stratified into mutant KRAS and WT KRAS samples. For a set of genes, qRT–PCR performed on colon and pancreatic representative cancer cell lines showed concordant expression trends when comparing colon-dominant KRAS mutants versus WT KRAS and dominant pancreatic KRAS mutants versus WT KRAS, as expected according to in silico analyses.

Conclusions

Our findings may provide insight into the common transcriptional signatures potentially underlying colon and pancreatic KRAS-mutant cancers. However, further studies are needed to elucidate the diagnostic and prognostic value of targets identified as common features in our study.

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.