The role of protein biomarkers in cancer treatment has long fascinated the medical research community, offering a potential pathway toward more personalized and effective therapies. In a groundbreaking new study published in BMC Cancer, researchers from China have uncovered compelling evidence linking the expression of protein arginine methyltransferase 5 (PRMT5) with chemotherapeutic outcomes in colon cancer patients following surgery. Their findings suggest that PRMT5 could serve as a critical prognostic marker, shaping future adjuvant chemotherapy decisions.
Colon cancer remains one of the most prevalent malignancies worldwide, and although surgery is often curative for many patients, the risk of recurrence necessitates the use of postoperative adjuvant chemotherapy. Yet, not all patients derive equal benefit from chemotherapy, underscoring a growing need for reliable biomarkers to guide treatment strategies accurately. This study addresses this gap by focusing on PRMT5, an enzyme involved in arginine methylation, a critical post-translational modification that influences gene expression and cellular functions.
The investigatory team, led by Lu et al., employed immunohistochemistry (IHC) to assess PRMT5 protein levels in tumor tissues and corresponding paratumor samples taken from 199 colon cancer patients who had undergone radical surgery. This method allowed precise localization and quantification of PRMT5 within the tissue microenvironment, providing a direct window into its biological activity in cancer versus adjacent normal tissue.
The data revealed a significant overexpression of PRMT5 in tumor tissues compared to paratumoral counterparts. Such upregulation aligns with previous research highlighting the oncogenic potential of dysregulated arginine methyltransferases in various cancers. Remarkably, this elevated PRMT5 expression was consistent regardless of several clinicopathological parameters, including patients’ age, sex, tumor location, differentiation grade, TNM staging, vascular invasion, and microsatellite instability status.
However, the distinguishing element of this investigation was the linkage of PRMT5 levels to the clinical outcomes specifically in the cohort receiving adjuvant chemotherapy. Patients classified as having high PRMT5 expression displayed a notably lower 5-year disease-free survival (DFS) rate—50% compared to 67.2% in patients with lower PRMT5 levels. This statistically significant difference (p = 0.039) suggests PRMT5 expression not only serves as a marker of tumor biology but also directly impacts chemotherapy efficacy.
Intriguingly, the non-chemotherapy subgroup did not exhibit any correlation between PRMT5 levels and survival outcomes, emphasizing the marker’s predictive rather than purely prognostic role. This nuance is critical, indicating PRMT5 may interact mechanistically with chemotherapeutic pathways, potentially influencing drug resistance or sensitivity.
Moreover, advanced multivariate analyses further solidified PRMT5’s role alongside established risk factors such as nodal involvement (N stage) and microsatellite status, collectively defining an independent set of predictors for poorer DFS in treated patients. These insights unveil an additional biochemical axis warranting consideration during postoperative management, with implications extending toward treatment customization.
At the molecular level, PRMT5 functions primarily as a methyltransferase that modifies arginine residues on histones and other proteins, thereby regulating chromatin structure and gene transcription. Aberrant PRMT5 activity has been implicated in sustaining proliferative signaling, evading growth suppressors, and promoting genomic instability—all hallmarks of cancer. Its elevated presence in colon cancer, therefore, may reflect an aggressive tumor phenotype characterized by altered epigenetic landscapes.
Since adjuvant chemotherapy typically employs agents such as fluoropyrimidines and oxaliplatin targeting rapidly dividing cells, PRMT5’s modulation of gene expression might interfere with chemotherapy-induced cytotoxicity. One plausible hypothesis is that high PRMT5 expression confers enhanced repair mechanisms or anti-apoptotic signaling, thereby diminishing drug efficacy.
The study’s results advocate for integrating PRMT5 testing into routine pathological assessment post-surgery, enabling oncologists to identify patients at heightened risk of chemoresistance. This stratification could foster more tailored approaches, potentially guiding the use of alternative regimens or incorporating PRMT5 inhibitors—an emerging class of targeted therapeutics under preclinical evaluation.
Furthermore, the absence of PRMT5’s impact on patients who did not receive chemotherapy underscores its specific relevance in the therapeutic context rather than as a universal prognostic factor. This distinction enriches our understanding of tumor biology, delineating the boundary between markers of disease aggression and those predicting treatment response.
While the current study’s retrospective design and reliance on immunohistochemical scoring warrant validation through larger prospective trials, the findings open promising avenues for translational research. Future investigations may focus on deciphering the molecular interplay between PRMT5 activity and chemotherapeutic agents, possibly unearthing novel synergistic drug targets.
In addition, the exploration of PRMT5 as a therapeutic target itself could revolutionize treatment paradigms. Early-phase inhibitors targeting PRMT5 have demonstrated anti-tumor activity in preclinical models, suggesting a dual benefit: direct tumor suppression and the potential restoration of chemosensitivity in patients harboring high PRMT5-expressing tumors.
Clinically, incorporating PRMT5 expression status could accelerate the move toward precision oncology in colon cancer, optimizing benefit-risk ratios for adjuvant chemotherapy and sparing patients from unnecessary toxicity when likely inefficacious. This personalized approach aligns with current trends aiming to harness molecular insights to improve survival and quality of life.
Beyond colon cancer, the broader implications resonate across oncology, as PRMT5 dysregulation is implicated in several malignancies, including lymphoma, lung cancer, and glioblastoma. Elucidating its universal or cancer-specific roles may provide a scaffold for multi-tumor biomarker panels or combination treatment strategies.
In summary, Lu and colleagues’ study represents a significant contribution to cancer biomarker research, identifying PRMT5 expression as a pivotal predictor of chemotherapy outcomes in colon cancer. The elucidation of this relationship not only advances biological understanding but also paves the way for enhanced clinical decision-making, offering hope for improved long-term patient survival through more intelligent therapy selection.
Subject of Research: Protein arginine methyltransferase 5 (PRMT5) expression as a biomarker for predicting postoperative chemotherapeutic outcomes in colon cancer patients.
Article Title: The expression of PRMT5 is associated with postoperative chemotherapeutic outcome in colon cancer.
Article References:
Lu, L., Li, H., Yin, H. et al. The expression of PRMT5 is associated with postoperative chemotherapeutic outcome in colon cancer. BMC Cancer 25, 760 (2025). https://doi.org/10.1186/s12885-025-14161-5
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14161-5
Keywords: PRMT5, colon cancer, adjuvant chemotherapy, biomarker, disease-free survival, immunohistochemistry, personalized medicine, epigenetics, chemoresistance
