Abstract
Simple SummaryDecision about treatment choice in early-stage colon cancer may be difficult for clinicians because of a lack of published data. Colon cancer is a very heterogeneous disease, but some previous efforts have helped us elucidate potential biomarkers for characterizing patients. Our goal is to create a panel of biomarkers capable of differentiating patients with a low, medium, and high risk of death or relapse. Our results suggest that, by combining PD-L1, GLUT-1, and mismatch repair proteins in a biomarker panel, patients could be significantly and evenly divided into one of these three groups. The resulting biomarker panel has the potential clinical value that, by being able to classify a patient with early colon cancer as being at high risk of death or tumor evolution, they could benefit from a more aggressive early treatment, while this approach might not be needed for low-risk patients.Molecular characterization of colorectal cancer has helped us understand better the biology of the disease. However, previous efforts have yet to provide significant clinical value in order to be integrated into clinical practice for patients with early-stage colon cancer (CC). The purpose of this study was to assess PD-L1, GLUT-1, e-cadherin, MUC2, CDX2, and microsatellite instability (dMMR) and to propose a risk-panel with prognostic capabilities. Biomarkers were immunohistochemically assessed through tissue microarrays in a cohort of 144 patients with stage II/III colon cancer. A biomarker panel consisting of PD-L1, GLUT-1, dMMR, and potentially CDX2 was constructed that divided patients into low, medium, and high risk of overall survival or disease-free survival (DFS) in equally sized groups. Compared with low-risk patients, medium-risk patients have almost twice the risk of death (HR = 2.10 (0.99–4.46), p = 0.054), while high-risk patients have almost four times the risk (HR = 3.79 (1.77–8.11), p = 0.001). The multivariate goodness of fit was 0.756 and was correlated with Kaplan–Meier curves (p = 0.002). Consistent results were found for DFS. This study provides a critical basis for the future development of an immunohistochemical assessment capable of discerning early-stage CC patients as a function of their prognosis. This tool may aid with treatment personalization in daily clinical practice and improve survival outcomes.
Highlights
Colorectal cancer (CRC) is the second most common cause of cancer deaths worldwide [1]
This is the case for microsatellite instability (MSI) or mismatch repair (MMR) protein deficiency for adjuvant therapy and KRAS, BRAF (V600E), and PIK3CA for anti-epidermal growth factor therapy in the metastatic setting [4,5,6,7,8]
For Overall survival (OS), expression of PD-L1—L and glucose transporter 1 (GLUT-1)—H was statistically significant and independent, conferring a 52% reduction in the risk of mortality (HR = 0.48, 95% confidence intervals (CIs) (0.27–0.87), p = 0.016) and almost twice the risk of mortality (HR = 1.94, 95% CI (1.04–3.61), p = 0.036) respectively; similar results were found for disease-free survival (DFS)
Summary
Colorectal cancer (CRC) is the second most common cause of cancer deaths worldwide [1]. CRC is a highly heterogeneous disease; earlier efforts have helped us understand the molecular events that play a crucial role in prognosis and treatment decisions This is the case for microsatellite instability (MSI) or mismatch repair (MMR) protein deficiency for adjuvant therapy and KRAS (exon2), BRAF (V600E), and PIK3CA for anti-epidermal growth factor (anti-EGFR) therapy in the metastatic setting [4,5,6,7,8]. The previously mentioned characterization efforts have not been able to provide results of sufficient clinical significance to merit inclusion in international guidance and to change daily clinical practice These efforts have helped elucidate the main molecular signaling pathway aberrations and interactions, gene expression profiles, and pathological characteristics contributing to the complex tumoral evolution process [14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
