Genomic Profiling in Colorectal Cancer Reveals Prognostic Markers

Comprehensive genomic profiling (CGP) in colorectal cancer (CRC) is shedding light on the impact of specific mutations on patient outcomes, according to one study.¹ Although CGP-guided therapies did not produce a significant survival advantage, alterations in TP53 and SMAD4 were linked to worse prognosis, and PTEN mutations correlated with improved survival.

This prospective observational study is published in the Journal of Cancer Research and Clinical Oncology.

Next-generation sequencing shows limited survival benefit but identifies key mutations that may inform future treatment strategies. | Image credit: angellodeco-stock.adobe.com

“Performing CGP before the standard-of-care treatment in patients with advanced solid tumors may provide a clinical beneficial strategy for guiding precision therapy,” wrote the researchers of the study. “These single-arm prospective trials have collectively supported the efficacy of CGP in informing genotype-based therapeutic decisions.”

CGP uses next-generation sequencing to analyze hundreds of cancer-related genes and key biomarkers such as tumor mutational burden, microsatellite instability, and homologous recombination deficiency in a single test.² By requiring less tissue and reducing turnaround time compared with multiple conventional assays, CGP supports personalized medicine by guiding diagnosis, treatment selection, and prognosis. Advances such as RNA fusion assays, liquid biopsy, lower sequencing costs, improved bioinformatics tools, and broader reimbursement have expanded access to CGP, enabling more patients to benefit from precision oncology and clinical trial opportunities.

The study was conducted at a single hospital between September 2019 and March 2024. A total of 100 patients with CRC underwent CGP using 4 different next-generation sequencing (NGS) platforms.¹ Clinical data, including age, performance status, and treatment history, were collected. Patients were categorized based on whether they received CGP-guided therapy or standard care. Overall survival (OS) was compared between these groups, and associations between specific genomic alterations and OS were analyzed to identify potential prognostic markers.

Among the patients with CRC who underwent CGP, most had a good performance status. The most frequent alterations identified were TP53 (82%), APC (82%), and KRAS (55%). Actionable mutations, including ERBB2 amplification and BRAF V600E, were detected in a subset of patients, with 9% ultimately receiving CGP-guided therapy. These patients achieved a longer overall survival from expert panel discussion compared with those who did not (16.0 vs. 10.8 months), although the difference did not reach statistical significance.

Genomic analysis also revealed that alterations in TP53, SMAD4, and NF1 were associated with worse outcomes, whereas PTEN mutations correlated with improved survival. TP53 mutations were more frequently observed in left-sided CRCs.

However, the researchers acknowledged some limitations. First, the study was conducted at a single institution and had a small sample size. Additionally, only a few patients received CGP-guided therapy, most of whom had microsatellite-stable/tumor mutational burden-high disease with poor response to immunotherapy. Furthermore, the outcomes may have also been influenced by the evolving definition of actionable alterations. Therefore, the researchers noted that larger, multicenter trials are needed to confirm the clinical utility of CGP in CRC.

Despite these limitations, the researchers believe these findings point to potential targets for future treatment development and more personalized approaches to CRC care.

“In conclusion, 9% of CRC patients in our study received CGP-based therapy, however, a statistically significant survival benefit was not observed,” wrote the researchers. “However, TP53 and SMAD4 mutations were identified as negative prognostic markers, indicating their potential as targets for future drug development and clinical trials.”

References

1. Tanabe H, Ando K, Takahashi K, et al. Clinical utility of comprehensive genomic profiling test for colorectal cancer: a single institution prospective observational study. J Cancer Res Clin Oncol. 2025;151(9):253. doi:10.1007/s00432-025-06295-7

2. Tjota MY, Segal JP, Wang P. Clinical utility and benefits of comprehensive genomic profiling in cancer. J Appl Lab Med. 2024;9(1):76-91. doi:10.1093/jalm/jfad091