Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Unraveling the role of molecular profiling in predicting treatment response in stage III colorectal cancer patients: Insights from the IDEA International Study

Ippokratis Messaritakis
* ORCID logo ,
Eleni Psaroudaki
,
Konstantinos Vogiatzoglou
,
Maria Sfakianaki
,
Pantelis Topalis
ORCID logo ,
Ioannis Iliopoulos
,
Dimitrios Mavroudis
,
John Tsiaoussis
ORCID logo ,
Nikolaos Gouvas
,
Maria Tzardi
,
Ioannis Souglakos
Version 1 : Received: 17 August 2023 / Approved: 18 August 2023 / Online: 18 August 2023 (10:51:10 CEST)

A peer-reviewed article of this Preprint also exists.

Messaritakis, I.; Psaroudaki, E.; Vogiatzoglou, K.; Sfakianaki, M.; Topalis, P.; Iliopoulos, I.; Mavroudis, D.; Tsiaoussis, J.; Gouvas, N.; Tzardi, M.; Souglakos, J. Unraveling the Role of Molecular Profiling in Predicting Treatment Response in Stage III Colorectal Cancer Patients: Insights from the IDEA International Study. Cancers 2023, 15, 4819. Messaritakis, I.; Psaroudaki, E.; Vogiatzoglou, K.; Sfakianaki, M.; Topalis, P.; Iliopoulos, I.; Mavroudis, D.; Tsiaoussis, J.; Gouvas, N.; Tzardi, M.; Souglakos, J. Unraveling the Role of Molecular Profiling in Predicting Treatment Response in Stage III Colorectal Cancer Patients: Insights from the IDEA International Study. Cancers 2023, 15, 4819.

Abstract

Background: This study aimed to investigate the molecular profiles of stage III CRC patients from the international IDEA study. It also sought to correlate these profiles with Toll-like and vitamin D receptor polymorphisms, clinicopathological and epidemiological characteristics, and patient outcomes. Methods: Whole Exome Sequencing and PCR-RFLP on surgical specimens and blood samples, respectively, were performed to identify molecular profiling and the presence of Toll-like and vitamin D polymorphisms. Bioinformatic analysis revealed mutational status. Results: Among the enrolled patients, 63.7% were male, 66.7% had left-sided tumors, and 55.7% received CAPOX as adjuvant chemotherapy. Whole exome sequencing identified 59 mutated genes in 11 different signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) CRC panel. On average, patients had 8 mutated genes (range, 2-21 genes). Mutations in ARAF and MAPK10 emerged as independent prognostic factors for reduced DFS (p=0.027 and p<0.001, respectively), while RAC3 and RHOA genes emerged as independent prognostic factors for reduced OS (p=0.029 and p=0.006, respectively). Right-sided tumors were also identified as independent prognostic factors for reduced DFS (p=0.019) and OS (p=0.043). Additionally, patients with tumors in the transverse colon had mutations in genes related to apoptosis, PIK3-Akt, Wnt, and MAPK signaling pathways. Conclusions: Molecular characterization of tumor cells can enhance our understanding of the disease course. Mutations may serve as promising prognostic biomarkers, offering improved treatment options. Confirming these findings with require larger patient cohorts and international collaborations to establish correlations between molecular profiling, clinicopathological and epidemiological characteristics and clinical outcomes.

Keywords

colorectal cancer; stage III; molecular profiling; IDEA study; whole exome sequencing; bioinfor-matics

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.