BACKGROUND:This prospective Phase 2 trial assessed a novel de-escalation strategy for upfront neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (NAC-TPF) to avoid postoperative radiotherapy (PORT) and chemoradiotherapy (POCRT) for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS:Patients with HPV-associated resectable OPSCC were enrolled. Invasive surgery or PORT/POCRT was an inclusion criterion if upfront surgery was performed. Treatment started with three cycles of NAC-TPF, followed by surgery. The primary endpoint was the centrally reviewed pathological complete response (pCR) rate after NAC-TPF. Levels of high-risk HPV RNA in tumor specimens and plasma circulating tumor (ct) HPV DNA, and quality of life (QOL) scores were assessed. RESULTS:Of 32 eligible patients, 30 patients underwent transoral surgery after NAC-TPF. R0 resection was confirmed in 31 patients. pCR and virological complete response rate at both the primary site and lymph nodes were 65.6% and 64.5%, respectively. No PORT/POCRT was performed in 91%. All QOL scores recovered to baseline values or improved within 1 year. Twenty-three patients showed undetectable ctHPV DNA levels after NAC-TPF. CONCLUSION:Although the primary endpoint was not met, NAC-TPF in HPV-associated resectable OPSCC achieved clinically meaningful pCR, enabling avoidance of PORT/POCRT in the majority of patients. (Clinical trial registration numbers: jRCT1041220029).
BACKGROUND:Optimal dosing of the programmed death-1 (PD-1) inhibitor pembrolizumab remains poorly defined. Dosing has been guided by achieving complete peripheral receptor occupancy, which may not reflect immune activation. We investigated relationships between dose, systemic and intratumoural pharmacokinetics, receptor occupancy, and immune activation in non-small cell lung cancer. METHODS:A physiological pharmacokinetic model describing plasma and intratumoural kinetics was extended with receptor occupancy and interleukin-2 (IL-2) induction parameters derived from ex vivo experiments. Simulations compared three approved regimens-2 mg/kg Q3W, 200 mg Q3W, and 400 mg Q6W. RESULTS:All regimens produced near-complete PD-1 receptor occupancy in both compartments. Despite this, IL-2 concentrations were predicted to change throughout the dosing interval, tracking pembrolizumab concentration rather than receptor occupancy. The 400 mg Q6W regimen yielded the highest IL-2 levels. Changes in intratumoural IL-2 concentration were less pronounced than in plasma. CONCLUSION:Receptor occupancy did not predict immune activation, suggesting it's an inadequate pharmacodynamic surrogate for pembrolizumab. These findings challenge current PD-1 inhibitor dose selection strategies and highlight the need for robust pharmacodynamic markers and clearer definition of the immune activation required for optimal efficacy.
BACKGROUND:The prognostic significance of PD-L1 expression in unresectable/recurrent gastric cancer treated by first-line chemotherapy without an immune checkpoint inhibitor (ICI) remains unclear. The phase III trial JCOG1013 demonstrated no overall survival (OS) or progression-free survival (PFS) benefit of docetaxel/cisplatin/S-1 over cisplatin/S-1. This ancillary analysis of JCOG 1013 evaluated the prognostic value of PD-L1 expression. METHODS:PD-L1 expression was assessed in pretreatment tumor specimens using the Dako 28-8 pharmDx assay. Combined positive score (CPS) and tumor proportion score (TPS) were calculated. PD-L1 positivity was defined as CPS ≥ 5 or TPS ≥ 1%. Univariable and multivariable analyses were performed for OS and PFS. RESULTS:Among 741 patients enrolled in JCOG1013, 540 patients were included. In univariable analyses, neither CPS ≥ 5 nor TPS ≥ 1% was significantly associated with OS or PFS. In multivariable analyses, CPS ≥ 5 was not significantly associated with OS (HR 0.86, 95% CI 0.71-1.04; p = 0.127) or PFS (HR 0.92, 95% CI 0.77-1.11; p = 0.392); however, TPS ≥ 1% was significantly associated with longer OS (HR 0.78, 95% CI 0.62-0.97; p = 0.028) and PFS (HR 0.76, 95% CI 0.62-0.94; p = 0.012). CONCLUSIONS:TPS ≥ 1% is an independent favorable prognostic factor for survival in patients with unresectable/recurrent gastric cancer receiving chemotherapy alone. CLINICAL TRIAL REGISTRATION:UMIN000007652.
Radiomics has been widely explored as a non-invasive biomarker in head and neck squamous cell carcinoma (HNSCC), yet its clinical role remains unclear. Tissue-based biomarkers differ in their susceptibility to spatial sampling. Biomarkers such as PD-L1 expression, immune-cell infiltration, necrosis, and immune exclusion may exhibit substantial spatial heterogeneity, whereas HPV/p16 status and some genomic alterations are generally more stable across the tumor. Nevertheless, localized sampling may incompletely capture heterogeneity in selected clinical contexts. This mismatch becomes clinically relevant when treatment decisions, particularly for chemoradiotherapy, immunotherapy, or de-escalation, are based on potentially non-representative biopsy findings. In this narrative review, we argue that the role of radiomics is not to outperform established biomarkers, but to contextualize them by capturing spatial heterogeneity related to hypoxia, necrosis, stromal architecture, and immune exclusion. We synthesize current evidence linking radiomic features to these biological processes and map them to specific clinical decision points, including larynx preservation, immunotherapy stratification, and recurrence assessment. Rather than serving as a standalone predictor, radiomics may provide complementary spatial information that helps identify situations in which biopsy-derived biomarkers should be interpreted with caution. Although current evidence is largely retrospective, radiomics offers a pragmatic framework for integrating spatial information into biomarker-guided clinical workflows.
BACKGROUND:Elevated serum triglycerides (TG) are associated with poor prognosis in non-small cell lung cancer (NSCLC), but the mechanisms underlying this association remain unclear. Elucidating the role of TG in NSCLC metastasis may reveal novel therapeutic targets. METHODS:A retrospective analysis was performed in 77 NSCLC patients stratified by serum TG levels. Survival was assessed using Kaplan-Meier analysis, and metastasis rates were compared using chi-square tests. Hypertriglyceridemia was modelled in mice. Extracellular matrix (ECM)-constrained invasion assays were conducted in NSCLC cell lines. Lipid β-oxidation and RhoA signalling were interrogated using pharmacological inhibition and genetic silencing of CPT1A and RhoA. RESULTS:Patients with hypertriglyceridemia (TG > 2.3 mmol/L) had significantly shorter overall survival (log-rank p = 0.009) and higher rates of lymph node metastasis (84.4% vs. 37.9%) and distant metastasis (31.3% vs. 3.4%) than normotriglyceridemic patients (TG < 1.7 mmol/L). Mechanistically, TG enhanced lipid β-oxidation, activating RhoA-driven cytoskeletal remodelling that enabled tumour cells to overcome ECM confinement and acquire metastatic competence. Pharmacological inhibition or genetic silencing of CPT1A or RhoA significantly suppressed TG-induced invasion and metastasis. CONCLUSIONS:Elevated serum TG promotes NSCLC metastasis through a lipid β-oxidation-RhoA-cytoskeletal axis. Targeting lipid catabolism and cytoskeletal dynamics may represent a therapeutic strategy for hypertriglyceridemia-associated NSCLC.
Pathology is central to many biologically driven cancer clinical trials. Biomarker-led and translational studies depend on robust tissue pathways, cellular and molecular assays, pathology-derived endpoints, and clinically meaningful interpretation of discovery science. Where trials depend on tumour material, biomarker-defined eligibility or mechanism-focused endpoints, pathology expertise should be embedded early, before protocols, budgets, and assays are fixed. Early pathology input strengthens feasibility, specimen governance, assay selection, quality assurance, and the long-term value of collected samples. In the UK, the Clinical Trials Pathology Advisory Group, now within the new Pathological Society of Great Britain and Ireland Clinical Trials Pathology subcommittee, provides a practical route for pre-submission specialist review. This Perspective argues that pathology is core infrastructure for biologically rich trials, linking discovery science to clinical translation.
BACKGROUND:The PD-L1 combined positive score (CPS) is a biomarker predicting responses in gastric cancer (GC) immunotherapy. OBJECTIVES:We aimed to develop a deep learning-based model to predict responses to nivolumab in GC using PD-L1 28-8 immunohistochemistry. METHODS:A cell-detection network was trained on 1927 patches from 88 whole-slide images to generate a computational positive cell ratio (cPCR). The predictive performance of cPCR was evaluated in an independent cohort of 147 patients treated with nivolumab plus chemotherapy. RESULTS:The overall objective response rate (ORR) was 49.66%. ORR was 56.12% in patients with PD-L1 CPS ≥ 5 and 36.73% in those with CPS < 5. Using cPCR, ORR was 56.03% for cPCR ≥5 and 25.81% for cPCR <5. The AUCs of CPS (0.586) and cPCR (0.601) did not differ significantly, but net reclassification analysis showed superior predictive performance for cPCR (p = 0.0269). Incorporating cPCR with tumour-stroma ratio through stepwise variable selection enabled construction of a risk-score model that improved prediction of immunotherapy benefit. CONCLUSIONS:In conclusion, we developed a cPCR-based model and risk-score system that more accurately forecasts nivolumab response in GC, offering a promising tool for optimising immunotherapy selection.
BACKGROUND:G protein-coupled receptors (GPCRs) are the largest class of membrane-bound receptors and are emerging as targets for the effective treatment of cancer. The role of orphan GPCR GPR52 in cancer has not been characterized. Low mRNA expression of GPR52 in breast tumours correlates with reduced overall survival, leading to the hypothesis that loss of GPR52 supports breast cancer progression. METHODS:CRISPR-Cas9 was used to knock out GPR52 in the human triple-negative breast cancer cell lines MDA-MB-468 and MDA-MB-231. 2D and 3D in vitro studies, electron microscopy, and a zebrafish xenograft model were used to assess the morphology and behaviour of GPR52 KO cells. RESULTS:Loss of GPR52 was associated with elevated levels of cAMP, increased cell-cell interaction in 2D cultures, more spindle-like morphology on collagen, altered 3D spheroid morphology, and increased propensity to organize and invade collectively. Zebrafish injected with GPR52 KO cells developed a greater total cancer area than control. RNA sequencing and proteomic analyses of GPR52-null cells revealed an increased cAMP signalling signature. Re-expression of GPR52 and inhibition of cAMP production rescued some GPR52 KO phenotypes. CONCLUSIONS:GPR52 loss is a potential mechanism by which breast cancer progression may occur and supports the investigation of GPR52 agonism as a therapeutic option for breast cancer. STATEMENT OF SIGNIFICANCE:Loss of the orphan GPCR GPR52 in human breast cell lines leads to increased cell clustering, hybrid/partial EMT, and increased tumour burden in zebrafish, further expanding our understanding of mechanisms driving cancer progression and opening the door to novel therapeutic approaches.
BACKGROUND:Neoadjuvant chemoimmunotherapy (NACI) has revolutionized head and neck squamous cell carcinoma (HNSCC) treatment. However, some patients still do not respond significantly, partly attributed to insufficient anti-tumor specific T-cells. Thus, identifying the underlying causes of impaired antitumor immunity has become an urgent priority to improve efficacy. METHODS:To investigate the link between anti-tumor specific T cells and NACI efficacy in treating HNSCC, we employed multicolor immunohistochemistry (mIHC) and single-cell RNA sequencing (scRNA-seq). To gain deeper insights into the regulatory mechanisms of these T cell populations, we performed cell-cell interaction analysis and spatial analysis. Furthermore, co-culture experiments were carried out to explore the interactions between the cells. RESULTS:Our scRNA-seq results indicated that the population of CD39+CD103+ (double-positive, DP) CD8+ T cells was dramatically increased in the responders of NACI-treated HNSCC patients, while mIHC analysis confirmed the correlation between DP CD8+ T cells density and NACI response. Functional assays demonstrated that DP CD8+ T cells constitute a distinct T cell subset exhibiting enhanced cytotoxic activity. The cell-cell interaction analysis revealed that DP CD8+ T cells were regulated by the CD90+CD138+ cancer-associated fibroblasts (CAFs) subset, which has been characterized as desmoplastic CAFs (dCAFs). In vitro mechanistic experiments suggested that CD90+CD138+ CAF-derived LAMA-4 may reduce the antitumor capacity of DP CD8+ T cells. CONCLUSIONS:Our study highlights the critical role of DP CD8+ T cells in enhancing NACI efficacy. Meanwhile, further research is warranted to explore the effects of targeting CD90+CD138+ CAFs,a thus regulating the function of DP CD8+ T cells.
BACKGROUND:Liver cancer remains a major global challenge, with limited benefit from immune checkpoint inhibitors due to strong immune evasion. Emerging evidence indicates that chromatin modifiers shape tumor immunogenicity, but their roles in liver cancer immunity are not fully understood. METHODS:We investigated the role of the histone demethylase KDM2A in liver cancer using genetic silencing in vitro and in vivo. We evaluated mitochondrial function, redox balance, genomic stability, and performed transcriptomic and epigenomic analyses to assess immune pathway changes and H3K36me2 distribution. Immune infiltration was analyzed in human liver tumors and syngeneic mouse models. RESULTS:KDM2A silencing caused mitochondrial dysfunction, redox imbalance, and DNA damage, leading to activation of innate and adaptive immune pathways. It also reshaped H3K36me2 deposition at loci regulating chemokine signaling, metabolism, and T-cell recruitment. In human liver tumors, high KDM2A expression correlated with poor differentiation, macrophage enrichment, and exclusion of CD8⁺ T cells, consistent with an immune-excluded phenotype. In syngeneic models, KDM2A loss increased intratumoral CD8⁺ T-cell infiltration. CONCLUSIONS:KDM2A acts as a key epigenetic regulator of mitochondrial function, genomic stability, and the tumor immune microenvironment in liver cancer. Targeting KDM2A may enhance tumor immunogenicity and improve responses to immunotherapy, representing a promising therapeutic strategy.
B7 homologue 3 (B7-H3) is a promising therapeutic target in oncology. While its expression on tumour cells is well established, its distribution and role within the tumour microenvironment (TME) remain less clearly defined. This review systematically evaluates B7-H3 protein expression across human TME compartments and explores reported associations with tumour progression and clinical outcomes. A comprehensive literature search was conducted up to June 2025, identifying studies that assessed and quantified B7-H3 expression in the TME of solid human tumours. Thirty-one studies met the inclusion criteria. B7-H3 expression was frequently reported in tumour-associated vasculature, where higher levels have been reported to associate with aggressive histopathological features and reduced survival. Stromal expression, predominantly in cancer-associated fibroblasts, was identified in over half of the tumour types studied and was associated with immune evasion and stromal remodelling gene signatures, although findings varied across studies. Within the immune compartment, B7-H3 was most abundantly expressed in myeloid-derived suppressor cells, macrophages, and dendritic cells, and has been reported to associate to immunosuppressive phenotypes, advanced disease stage and poorer clinical outcomes. These findings identify tumour vasculature and myeloid-derived cells as B7-H3-positive compartments within the TME, although their clinical and therapeutic relevance requires further validation. PROSPERO registration number: CRD420251129792
BACKGROUND:Recurrent infections in the urinary tract may promote urologic cancer through chronic inflammation. However, evidence linking infections and the subsequent risk of urologic cancer has been conflicting, and long-term risk remains uncertain. METHODS:In this population-based descriptive cohort study, we included all Danish adults with a first-time hospital discharge diagnosis of recurrent cystitis during 2006-2022 in the Danish National Patient Registry, excluding patients with prior cancer. Urologic cancer diagnoses were ascertained through the Danish Cancer Registry. We calculated cumulative incidences and standardised incidence ratios (SIRs) using incidence rates from the general population. RESULTS:Among 42,377 patients (68% women, median age 62 years), 1047 were diagnosed with urologic cancer (median follow-up 5.7 years). The 1-year risk of any urologic cancer was 1.2% (95% confidence interval [CI], 1.1-1.3%). The corresponding 1-year SIR was 4.99 (95% CI, 4.56-5.44). Beyond 2 years of follow-up, the SIR remained elevated among women only at 1.47 (95% CI, 1.20-1.78). CONCLUSIONS:The elevated short-term risk suggests that recurrent cystitis is a clinical marker of urologic cancer. Yet, with low absolute risks, our results do not suggest additional diagnostic cancer work-up in these patients. In women, long-term risks for urologic cancer remained elevated.
BACKGROUND:Response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC) is heterogeneous. The Neoadjuvant Rectal (NAR) score quantifies treatment response via tumour downstaging and nodal status and correlates with survival outcomes. This work set out to explore whether low NAR and high NAR tumours represent biologically distinct groups pre-treatment. METHODS:Transcriptome microarrays quantified RNA expression within pre-treatment biopsies from LARC patients in GSE87211 and S:CORT consortium Grampian datasets. A validation cohort from the Beatson West of Scotland Cancer Centre was analysed using multiplex immunofluorescence and H&E-derived tumour-stromal ratios. RESULTS:Seventeen MSigDB Hallmarks were enriched in high NAR tumours; 'Epithelial-Mesenchymal Transition' was notably enriched (padj < 0.001). Immune-related signatures were enriched in low NAR tumours (p < 0.25). Both cohorts showed higher Microenvironment Cell Population counter 'Cytotoxic Lymphocytes' in low NAR (p < 0.05) and more stromal cells ('Endothelial Cells', 'Fibroblasts'; p < 0.05) in high NAR tumours. CD8 densities confirmed higher immune infiltration in low NAR tumours. DISCUSSION:Pre-treatment biopsies show consistent microenvironmental differences between high and low NAR tumours. While immune and stromal features are associated with response, the observed differences are insufficient to serve as standalone predictive biomarkers.
BACKGROUND:Cytidine triphosphate synthase 1 (CTPS1), a rate-limiting enzyme in nucleotide biosynthesis, is frequently upregulated in cancers. However, its functional role and therapeutic potential in lung adenocarcinoma (LUAD) remain poorly defined. METHODS:We integrated proteomic analyses, tissue microarrays, and functional assays to evaluate CTPS1 expression and clinical significance in LUAD. Genetic knockdown and pharmacological inhibition with the selective inhibitor STP938 assessed malignant phenotypes. The therapeutic efficacy of STP938, alone or combined with osimertinib, was evaluated in xenograft models. Integrated proteomic and transcriptomic analyses explored underlying mechanisms. RESULTS:CTPS1 was significantly upregulated in LUAD and associated with lymph node metastasis and poor overall survival (OS), serving as an independent prognostic factor. CTPS1 promoted proliferation, migration, and invasion while suppressing apoptosis. STP938 inhibited tumour growth in vitro and in vivo, and enhanced the efficacy of osimertinib in EGFR-mutant models. Multi-omics analyses identified MX1-associated interferon signalling as a downstream pathway, with MX1 expression positively correlating with CTPS1 and poor prognosis. CONCLUSIONS:CTPS1 drives LUAD progression and is linked to MX1-associated interferon signalling. Targeting CTPS1 with STP938, alone or in combination with osimertinib, represents a promising therapeutic strategy and supports CTPS1 as a targetable vulnerability in LUAD.
The incidence of endometrial cancer is rising globally, placing significant burden on diagnostic pathways for women with abnormal uterine bleeding. Current evaluation relies primarily on transvaginal ultrasound followed by invasive endometrial visualisation and sampling, although most symptomatic women have no sinister underlying pathology. Urine offers a promising non-invasive and easily repeatable biofluid capable of capturing tumour-associated signals through both systemic renal filtration and locally shed uterine material. This review summarises emerging evidence on urinary biomarkers for endometrial cancer detection, including somatic mutations, DNA methylation markers, proteins and peptides, vibrational spectroscopy signatures, microRNAs, metabolites and urine cytology. These biomarkers collectively reflect key biological processes driving endometrial carcinogenesis, including hormonal and metabolic dysregulation, immune activation, epithelial-stromal disruption, cellular proliferation and genomic instability. Among current candidates, DNA methylation panels and mutation-based assays have demonstrated encouraging diagnostic performance, with studies reporting sensitivities and specificities exceeding 80-90% in symptomatic populations. Urine cytology also shows strong diagnostic potential in selected cohorts, while metabolomic, proteomic and spectroscopy-based approaches remain promising but require further standardisation and prospective validation. Although not yet suitable for population screening, urinary biomarkers show considerable potential for risk stratification and triage of symptomatic women, potentially reducing unnecessary invasive investigations. Clinical translation will require standardised protocols, multi-centre validation and integration into existing diagnostic pathways.
BACKGROUND:While PDZ-LIM domain-containing protein (PDLIM2) suppresses lung cancer, its clinical significance and therapeutic potential remain to be fully explored. METHODS:Next-generation sequencing and immunohistochemistry of programmed death ligand 1 (PD-L1) were performed on lung adenocarcinoma (LUAD) tissues from 15,765 patients. PDLIM2 gene therapy was tested in syngeneic LUAD mouse models using intravenous nano-complexed plasmid DNA, alone or with chemoimmunotherapy. RESULTS:PDLIM2-high tumors were more common in primary/local biopsies versus metastatic samples (73.1% vs 53.0%; p < 0.001). High PDLIM2 expression was linked to lower mutation rates in RB1, TP53, SMARCA4, STK11, and KEAP1, but increased EGFR mutations (all p < 0.01). PDLIM2-high tumors also showed increased immune cell infiltration, T cell-inflamed scores, and PD-L1 positivity (all p < 0.008). High PDLIM2 was associated with improved survival (24.1 vs 18.1 months; p < 0.001, HR = 0.84) and remained prognostic in multivariate analysis (HR = 0.88, 95% CI 0.83-0.93), as well as with longer pembrolizumab time, especially with platinum-based therapy (p = 0.012, HR = 0.867). In two LUAD mouse models, nanoPDLIM2 improved median overall survival versus chemoimmunotherapy alone (10-12.5 vs 8-9 days; N = 8; p = 0.0001, 0.0003). CONCLUSION:PDLIM2 is a promising prognostic biomarker in LUAD linked to immune-receptive tumors. Preclinically, PDLIM2-based therapy enhances chemoimmunotherapy efficacy, though its predictive role warrants further evaluation.
Neuroblastoma is characterised by extensive genomic instability despite a marked paucity of recurrent somatic mutations. Instead, the disease is predominantly driven by chromosomal alterations, including segmental chromosomal imbalances, small structural variants, and oncogene amplification. A major unmet challenge is identifying key oncogenic drivers, beyond MYCN amplification, hidden within these recurrent DNA copy number alterations. Extra wild-type gene copies can alter expression levels and thus contribute to tumour development and affect survival. Increasing evidence suggests that these copy number-affected genes confer resistance to replication stress, a hallmark of high-risk neuroblastoma tumours. Among the most frequent and prognostically significant alterations is the gain of chromosome 17q. In this review, we discuss selected top-ranked candidate genes on 17q implicated in replication fork dynamics and DNA damage repair that we previously identified through an integrative functional genomics study. Improved understanding of the mechanisms by which 17q copy number-driven genes regulate replication stress responses and DNA damage repair may expose fundamental vulnerabilities in aggressive neuroblastoma and guide the development of novel targeted therapeutic strategies.
BACKGROUND:Smokers are eligible for lung cancer screening using low dose CT (LDCT) if they have a sufficiently high risk of lung cancer. In England, for example, people are eligible if their estimated risk using either of two validated models (PLCOm2012 and Liverpool Lung Project) exceeds a certain threshold. Risk is often estimated using only cigarette consumption (duration and number per day), yet many smokers also use other cancer-causing tobacco products. METHODS:SUMMIT is a prospective cohort study of a LDCT screening service. We evaluated the impact of cigars, pipes, and cigarillos on lung cancer risk. RESULTS:Among 13,000 participants who were current/former cigarette smokers, 511 (1 in 25) were also regular users of cigars, pipes, or cigarillos. The 5-year cumulative lung cancer incidence in people who currently smoked both types of tobacco products was 8.85%, versus 5.74% for cigarette only current smokers. Among these 511 participants, the percentage whose risk was below the screening eligibility threshold ignoring other tobacco products which then exceeded the threshold including these products was 0.6% using LLPv2, and 8.2% using PLCOm2012. CONCLUSIONS:All tobacco consumption should be considered when determining screening eligibility to avoid missing those who can benefit from LDCT. CLINICAL TRIAL REGISTRATION:Clinicaltrials.gov no: NCT03934866.
OBJECTIVE:Aldo-keto reductase 1B10 (AKR1B10) is a novel serum marker for hepatocellular carcinoma (HCC). This study was aimed to evaluate its clinical value in the diagnosis and immediate postoperative monitoring for HCC. METHODS:A total of 1197 subjects were recruited from two study centers, including 185 patients with HCC who underwent radical resection and followed up for 3 months. Serum samples were collected from all participants for AKR1B10 and alpha-fetoprotein (AFP) tests, and imaging and clinical data were collected. RESULTS:Serum AKR1B10 in HCC patients markedly increased to 1384.31 ± 107.91 pg/ml. Receiver operating characteristic (ROC) curve analysis showed an area under curve (AUC) of 0.877, sensitivity of 71.2%, and specificity of 97.2% for AKR1B10 in HCC compared to 0.792, 62.7%, and 88.7% for AFP. For early HCC, serum AKR1B10 had an AUC of 0.855, sensitivity of 70.6%, and specificity of 94.4% compared to 0.744, 56.7%, and 86.7% for AFP. After radical resection of HCC, serum AKR1B10 rapidly decreased to the normal range within 3-5 days whereas AFP remained high. At 1-3 months after surgery, serum AKR1B10 was consistent with imaging data in 89.11% of patients with HCC, whereas AFP had only 70.41%. CONCLUSION:AKR1B10 is an effective serum marker for diagnosis of HCC and postoperative monitoring of HCC, with better clinical performance than AFP.
