Colorectal cancer (CRC) ranks among the most prevalent and lethal malignancies worldwide, with its complex pathogenesis involving a convergence of genetic, epigenetic, immunological, and environmental factors. As populations age globally, the incidence of CRC continues to rise, underscoring the urgent need to deepen our understanding of its molecular underpinnings. Recent research sheds new light on the interplay between tumor suppressor proteins, oncogenic mutations, and systemic inflammatory responses, offering promising avenues for prognostication and therapeutic intervention in CRC.
A groundbreaking study, soon to be published in BMC Cancer, delves into the plasma levels of three pivotal proteins—APC, KRAS, and TP53—and their relationship with inflammatory indices in colorectal cancer patients. This investigation harnessed cutting-edge molecular techniques, including real-time PCR for precise KRAS mutation detection and ELISA assays to quantify circulating protein levels, to unravel the complex biological crosstalk that shapes tumor progression.
At the core of this study lies the scrutiny of KRAS mutations, especially the G12V variant, which has long been implicated in aberrant signaling pathways that fuel oncogenesis. KRAS mutations are notorious for mediating resistance to targeted therapies in colorectal cancer, thus representing both a clinical challenge and a molecular hallmark with profound prognostic implications. The researchers’ focus on KRAS, alongside the tumor suppressors APC and TP53, exemplifies a comprehensive approach to elucidating cancer biology beyond the tumor microenvironment by probing systemic biomarkers.
Intriguingly, the data uncovered that inflammatory indices, specifically the monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR), were markedly elevated in CRC patients compared to healthy baselines. These indices, calculated from routine blood counts, function as surrogate markers reflecting the host’s inflammatory and immune status. Their increase correlates with tumor advancement and prognosis, mirroring the dynamic interaction between neoplastic cells and the host immune response.
A particularly compelling finding was the elevation of plasma TP53 protein levels in patients exhibiting progressive colorectal cancer, highlighting TP53’s dual role not only as an intracellular tumor suppressor regulating cell cycle and apoptosis but also as a potential circulating biomarker indicative of disease burden. Conversely, APC and KRAS protein levels in plasma did not exhibit significant variance between stages, suggesting that their tumor-suppressive or oncogenic roles may be primarily exerted within the intracellular milieu rather than reflected systemically.
The association of the G12V KRAS mutation with higher PLR values and poor prognosis adds a vital layer to our understanding of genotype-phenotype correlations in colorectal cancer. Since platelets actively participate in tumor metastasis, angiogenesis, and immune evasion, the increased PLR may indicate a pro-tumoral systemic environment fostered by oncogenic KRAS signaling. This link opens up potential clinical applications where PLR might serve as an accessible biomarker for KRAS mutation-driven aggressiveness.
Moreover, the study elucidates a significant relationship between inflammatory indices and the plasma levels of tumor suppressor proteins, particularly TP53 and APC. This finding implicates a sophisticated network in which systemic inflammation might influence or be influenced by tumor suppressor dynamics, potentially modulating tumor progression. Such insights underscore the necessity of viewing colorectal cancer as an integrative systemic disease rather than an isolated tissue pathology.
The clinical implications of these findings are manifold. Elevated inflammatory indices could assist clinicians in stratifying patients according to disease severity and progression risk. Monitoring circulating TP53 protein levels might offer a minimally invasive strategy to track tumor dynamics, especially in patients with advanced disease. Additionally, the detection of KRAS mutation subtypes through plasma analysis could refine personalized treatment regimens, steering therapeutic decisions toward targeted approaches or immunomodulatory interventions.
Technically, the utilization of real-time polymerase chain reaction (PCR) for KRAS mutation detection marks a significant enhancement in diagnostic precision. This method amplifies specific DNA sequences in real-time, offering quantifiable mutation detection that surpasses conventional sequencing in speed and sensitivity. Coupled with enzyme-linked immunosorbent assay (ELISA) for protein quantification, this dual molecular approach establishes a robust platform for correlating genetic alterations with functional protein expression.
The interplay between inflammation and cancer development, long acknowledged in oncological research, gains new granularity through this work. Chronic inflammation is acknowledged as a driving force in colorectal carcinogenesis, promoting DNA damage, cellular proliferation, and angiogenesis. The enhanced MLR, PLR, and NLR represent pivotal indicators of systemic inflammation, which may not only reflect tumor presence but actively participate in shaping the tumor microenvironment and metastatic potential.
This study also challenges the simplistic notion of tumor suppressor proteins functioning solely within cellular compartments by demonstrating their detectable plasma levels and associations with systemic changes. This posits that these proteins, or their fragments, may be secreted or released due to tumor cell turnover, necrosis, or other mechanisms, suggesting new dimensions in biomarker research and potential targets for liquid biopsy development.
Furthermore, the gender composition of the study population, encompassing both male and female patients, may provide preliminary insights into sex-specific variations in inflammatory responses and molecular profiles in CRC, although further focused studies are warranted to elucidate these differences conclusively.
Given the relatively modest sample size of 40 patients, the study’s findings evoke critical interest in the need for larger, multicenter trials to validate these biomarkers’ prognostic and diagnostic utility. Simultaneously, integrating these systemic biomarkers with imaging and histopathological data could yield multimodal prognostic models that enhance clinical decision-making.
In conclusion, these compelling revelations about suppressor protein plasma levels and inflammatory indices in colorectal cancer patients propel forward our comprehension of tumor biology. They foreground the potential of systemic biomarkers in complementing traditional diagnostics, offering non-invasive windows into malignancy dynamics, and paving the way for more personalized, precise oncology care. As colorectal cancer continues to challenge clinicians and researchers, studies like this illuminate paths toward improving patient outcomes through molecular and immunological lenses.
Subject of Research: Colorectal cancer; suppressor protein plasma levels; inflammatory indices; KRAS mutations; tumor progression
Article Title: Suppressor protein plasma levels and inflammatory indices in colorectal cancer patients
Article References:
Chigvinadze, N., Pantsulaia, I., Lejava, T. et al. Suppressor protein plasma levels and inflammatory indices in colorectal cancer patients. BMC Cancer 25, 774 (2025). https://doi.org/10.1186/s12885-025-14200-1
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14200-1
Keywords: colorectal cancer, TP53, APC, KRAS, inflammatory indices, MLR, PLR, NLR, plasma biomarkers, real-time PCR, ELISA, G12V mutation, tumor progression
