Prognostic Significance of Oxidative Stress Biomarkers and Novel Hematological Inflammatory Indices in Colorectal Cancer: A Prospective Observational Study
CRC was associated with increased circulating oxidative stress biomarkers, with MDA showing the most consistent relationships with systemic inflammatory parameters and survival outcomes, and MDA is identified as a promising candidate oxidative–inflammatory marker warranting external validation rather than an independently established prognostic biomarker.
Abstract
Background and Objectives: Oxidative stress and chronic inflammation are closely interconnected processes involved in colorectal cancer (CRC) development and progression. However, the relationships between oxidative stress biomarkers, emerging hematological inflammatory indices, clinicopathological characteristics, and survival outcomes remain insufficiently characterized. This study evaluated circulating levels of 8-epi-prostaglandin F2α (8-epi-PGF2α), malondialdehyde (MDA), and superoxide dismutase 1 (SOD1), together with conventional and novel inflammatory indices, including the mean corpuscular volume-to-lymphocyte ratio (MCVL) and cumulative inflammatory index (IIC), in patients with CRC. Materials and Methods: This prospective observational study included 140 patients with histologically confirmed CRC and 40 healthy controls. Serum concentrations of 8-epi-PGF2α, MDA, and SOD1 were measured by ELISA, and hematological inflammatory indices were calculated from complete blood counts. Associations with clinicopathological characteristics were evaluated using non-parametric analyses with correction for multiple testing where appropriate. Spearman correlations with false discovery rate correction were used to assess oxidative–inflammatory associations. Prognostic analyses included 24-month time-dependent receiver operating characteristic (ROC) analysis accounting for censoring, Kaplan–Meier analysis, and Cox proportional hazards regression for overall survival (OS) and progression-free survival (PFS). Results: CRC patients exhibited significantly higher serum levels of 8-epi-PGF2α (p = 0.016), MDA (p < 0.001), and SOD1 (p < 0.001) than controls. Oxidative stress biomarkers differed significantly across TNM stage, nodal status, and histological grade, although the observed patterns were not uniformly progressive with disease stage. After false discovery rate correction, MDA retained significant correlations with multiple hematological inflammatory parameters, whereas SOD1 showed a more restricted correlation profile and 8-epi-PGF2α showed no significant correlations. At 24 months, MDA demonstrated the highest time-dependent discrimination for OS (AUC = 0.920; bootstrap 95% CI: 0.834–0.978), whereas its discrimination for PFS was modest (AUC = 0.636; bootstrap 95% CI: 0.487–0.773). High MDA, defined by the internally derived 24-month threshold, was associated with shorter PFS after adjustment for age, sex, and TNM stage (HR = 2.49, 95% CI: 1.29–4.80; p = 0.006) and, separately, metastatic status (HR = 2.40, 95% CI: 1.22–4.72; p = 0.011). However, when modeled continuously, MDA was no longer significantly associated with PFS after multivariable adjustment. Conclusions: CRC was associated with increased circulating oxidative stress biomarkers, with MDA showing the most consistent relationships with systemic inflammatory parameters and survival outcomes. Its prognostic association with PFS was dependent on the modeling approach, while its high discrimination for 24-month OS should be interpreted cautiously because of the limited number and metastatic restriction of death events. These findings identify MDA as a promising candidate oxidative–inflammatory marker warranting external validation rather than an independently established prognostic biomarker.
Findings emphasise the vital function of inflammatory and oxidative stress pathways in GI pathologies and suggest these biomarkers hold promise for diagnostic and prognostic applications.
I. Sharba, S. Mohammed, Jinan Mohammed Zahid· Al-Kufa University Journal f...· 0 citations
Ulcerative colitis is a colonic inflammatory disease that is long-term. Inflammatory, oxidative stress, and molecular activation biomarkers could enhance the evaluation of the disease. The circulation of the miR-21 is also relevant in mucosal inflammation and its clinical significance in ulcerative colitis is yet to be determined. This study tries to measure circulating miR-21, oxidative stress biomarkers and inflammatory indices in patients with ulcerative colitis and to test associations between them and disease activity, fecal calprotectin and composite inflammatory oxidative stress indices. This case–control study included 121 adults recruited at the Teaching Hospital for Digestive and Liver Diseases, Medical City, Baghdad, from 9 February 2025 to 23 October 2025. A total of 88 patients who had confirmed ulcerative colitis and 33 healthy controls were included in the sample. There were active disease and remission. Standard immunochemical and colorimetric measures were taken of serum CRP, IL-6, MDA, TAC and SOD. qRT-PCR was used to determine the levels of circulating miR-21. Fecal calprotectin and Mayo endoscopic subscore also were noted. Correlations, group comparisons, effect sizes, ROC analysis and exploratory regression models were carried out. Compared with controls, patients with ulcerative colitis had higher CRP, IL-6, MDA, miR-21, fecal calprotectin, IOSI, and Advanced IOSI, and lower TAC and SOD (all p < 0.001). CRP, IL-6, MDA, fecal calprotectin, IOSI, Advanced IOSI, TAC and SOD were significantly higher in active disease than remission (all p < 0.001). The level of circulating miR-21 was higher in comparison to controls but lower in active disease than in remission (p = 0.026). There was a strong correlation between IOSI and Advanced IOSI and fecal calprotectin. There was very high discrimination of a number of markers in these results set using ROC including CRP, IL-6, fecal calprotectin, IOSI and Advanced IOSI. The results indicate that there is a strong association between ulcerative colitis, systemic inflammation and oxidative imbalance. It seems that circulating miR-21 can be relevant, yet its activity can vary in response to activity states, and be altered by treatment. Composite inflammatory-oxidative stress indexes were well-performing and potentially provide a convenient summary of multi-marker perturbation. Clinical adoption still needs to be externally validated.
Ahmed Abd Temur, N. F. Razooqi, Ibrahim Abdulkareem Sabri· Stallion Journal for Multidi...· 0 citations
Background/Objectives: Inflammatory and hematologic indices derived from routine blood tests have been increasingly investigated as prognostic biomarkers in multiple myeloma (MM). However, their clinical utility remains inconsistent, and data on novel composite indices, such as the mean corpuscular volume-to-lymphocyte ratio (MCVL) and the cumulative inflammatory index (IIC), are lacking in MM. Methods: We conducted a retrospective study including 122 patients with newly diagnosed MM. Hematologic and inflammatory indices were evaluated at baseline and after four cycles of induction therapy. Associations with progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier analysis, Cox regression models, and receiver operating characteristic (ROC) curve analysis. Results: Baseline inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune–inflammation index (SII), MCVL, and IIC, were not significantly associated with PFS or OS. ROC analysis demonstrated poor discriminative ability for all evaluated markers at both baseline and post-induction timepoints (AUC values close to or below 0.50). In contrast, post-induction inflammatory indices, particularly PLR, MLR, AISI, and SIRI, were significantly associated with PFS in both univariable and multivariable Cox regression analyses. Neither baseline nor post-induction MCVL and IIC showed independent prognostic value. Conclusions: Baseline inflammatory and erythrocyte-derived indices, including the novel composite markers MCVL and IIC, have limited prognostic utility in MM. In contrast, dynamic changes in inflammatory biomarkers during treatment may provide more clinically relevant information regarding disease progression. These findings support integrating longitudinal biomarker assessment into future risk stratification models for MM.
Alexandra-Ștefania Stroe-Ionescu, L. Boldeanu, A. Pǎtraşcu et al.· Biomedicines· 0 citations
Canine mast cell tumors (MCTs) exhibit heterogeneous biological behavior and provide a clinically relevant setting in which relationships between tumor phenotype and systemic redox homeostasis can be investigated. This exploratory prospective cohort study evaluated complementary circulating redox-related biomarkers representing hydroperoxide-derived oxidant products, antioxidant capacity, lipid peroxidation-related products, and oxidative DNA damage, and examined their associations with clinicopathological features of canine MCTs. Sixty-seven dogs with cytologically and histologically confirmed cutaneous or subcutaneous MCTs were included. Clinical staging was performed using cytological evaluation of lymph nodes, liver and spleen, and excised tumors were classified according to the Patnaik and Kiupel systems. Proliferative activity was assessed using Ki-67, and surgically excised lymph nodes were classified according to the Weishaar HN system. Serum reactive oxygen metabolites (d-ROMs), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG) and antioxidant capacity using the OXY-adsorbent test were measured before therapeutic intervention. In the unadjusted analysis, serum MDA concentrations were higher in dogs with Ki-67 >23 than in dogs with Ki-67 ≤23 (median 10.8 vs. 7.0 μmol/L; raw p = 0.0254); however, this comparison did not remain statistically significant after Bonferroni correction for the 12 formal inferential biomarker × clinicopathological comparisons (adjusted p = 0.3052). The estimated Hodges–Lehmann location shift was +3.00 μmol/L (unadjusted bootstrap 95% CI, 0.58–6.00). No evaluated biomarker–clinicopathological association remained statistically significant after multiplicity adjustment. The observed MDA–Ki-67 pattern should therefore be regarded as exploratory and hypothesis-generating rather than as evidence of established prognostic or clinical utility. Long-term data on recurrence, progression, and survival were not available; therefore, prognostic utility could not be evaluated. Larger prospective studies incorporating longitudinal outcomes are warranted.
Argyrios Ginoudis, D. Pardali, M. Mylonakis et al.· Antioxidants· 0 citations
Background: Acute myeloid leukemia (AML) is biologically heterogeneous and associated with poor outcomes. Although oxidative stress contributes to AML pathogenesis, the prognostic value of related biomarkers remains uncertain. Objective: This study aimed to evaluate associations between oxidative stress-related biomarkers and prognosis in adults with AML, focusing on overall survival (OS), complete remission (CR), relapse, relapse-free survival (RFS), event-free survival (EFS), and early mortality. Methods: This PRISMA-compliant systematic review was registered in PROSPERO (CRD420261364956). MEDLINE/PubMed, Scopus, Cochrane Library, Science Citation Index, ClinicalTrials.gov, and WHO ICTRP were searched from January 2015 through 31 July 2026. Eligible studies included adults with AML, oxidative stress-related biomarkers measured in biological samples, and extractable prognostic data. Risk of bias was assessed using QUIPS and certainty of evidence using GRADE. Results: Thirteen of 537 records met the inclusion criteria; 203 supplementary reports yielded no additional studies. Investigated biomarkers included ROS-related phenotypes, antioxidant and redox-regulatory genes, glutathione metabolism, iron/inflammation-related markers, and oxidative DNA damage indicators. Adverse outcomes were associated with ROS-related phenotypes, combined ROS/aldehyde dehydrogenase activity, GPX3, GSTP1, ferritin, gamma-glutamyl transpeptidase-to-albumin ratio, SOD1, and glutathione-related metabolic profiles. Conclusions: These biomarkers may have prognostic value, particularly for OS, but heterogeneity limits clinical application. Standardized validation and integration into applicable risk models are required.
Efthymia Papaioannou, Foteini-Maria Manouka, Marios-Lampros Theodorou Anagnostou et al.· The Scientist· 0 citations
Oxidative stress and systemic inflammation are considered key mechanisms linking obstructive sleep apnea (OSA) to cardiovascular disease. This study aimed to investigate the relationships among oxidative stress, nitrosative stress, inflammatory biomarkers, and echocardiographic alterations in OSA. This cross-sectional observational study included 72 adults with OSA, classified according to disease severity as mild, moderate, or severe. Clinical characteristics and echocardiographic parameters were assessed. Oxidative stress biomarkers—malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), nitric oxide (NO), oxidative stress index (OSI), and paraoxonase-1 (PON1); the nitrosative stress marker 3-nitrotyrosine (3-NT), inflammatory biomarkers—interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α); and N-terminal pro-B-type natriuretic peptide (NT-proBNP)—were determined using spectrophotometric and ELISA methods. Correlation and regression analyses were performed to evaluate associations between oxidative stress and inflammation. No significant differences in echocardiographic parameters, oxidative stress biomarkers, inflammatory markers, or NT-proBNP concentrations were observed across OSA severity categories (all p > 0.05). Patients with diabetes mellitus exhibited larger left and right atrial diameters and higher pulmonary artery systolic pressure values compared with non-diabetic patients (all p < 0.05). Significant positive correlations were identified between IL-6 and MDA (ρ = 0.364, p = 0.002), TOS (ρ = 0.259, p = 0.029), and OSI (ρ = 0.257, p = 0.030). The nitrosative stress marker 3-NT was also positively correlated with MDA, TOS, and OSI (all p < 0.05). In multivariable regression analyses adjusted for age, body mass index, and diabetes mellitus, MDA remained independently associated with IL-6 concentrations (B = 1.776, 95% CI 0.110–3.442, standardized β = 0.271, p = 0.037). Similarly, OSI remained independently associated with IL-6 (B = 0.043, 95% CI 0.003–0.083, standardized β = 0.277, p = 0.034). OSA severity was not associated with significant differences in oxidative stress, inflammatory, or echocardiographic parameters. However, oxidative stress biomarkers were strongly interrelated and remained significantly associated with IL-6 concentrations, suggesting a potential link between oxidative stress and systemic inflammation in patients with OSA. These findings support further investigation of oxidative stress pathways as biomarkers of disease-related biological activity in OSA.
Crina Veronica Zinveliu Bercian, D. Măgureanu, R. Pop et al.· International Journal of Mol...· 0 citations
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