Li Ren

Background and Purpose: Investigating the assessment of innovative serum indicators with elevated sensitivity and specificity is crucial for enhancing the early diagnosis and prognosis of HCC (Hepatocellular carcinoma). This study aimed to evaluate the efficacy of COPA (Coatomer Subunit Alpha) in diagnosing hepatocellular carcinoma and assessing the effectiveness of immunotherapy. Methods: This study included two cohorts: a diagnostic cohort comprising 81 healthy controls, 118 patients with benign liver diseases, and 81 patients with pathologically confirmed HCC, and an immunotherapy cohort comprising 131 HCC patients treated with PD-1/PD-L1 inhibitors. Serum COPA was measured by ELISA, while AFP and PIVKA-II were measured by electrochemiluminescence. Diagnostic performance and immunotherapy monitoring efficacy were then evaluated. Results: COPA is upregulated in serum and HCC tumor samples. The ROC analysis indicated that the diagnostic efficacy of COPA (AUC = 0.911) surpassed that of traditional biomarkers. Importantly, COPA retained favorable diagnostic performance in both AFP-negative and PIVKA-II-negative HCC patients. Dynamic monitoring revealed that when comparing PIVKAII and AFP with imaging-based efficacy assessments, serum COPA changes demonstrated superior consistency pre- and post-immunotherapy (Kappa of COPA = 0.73, P < 0.01). COPA expression was significantly elevated in HCC tissues compared with adjacent non-tumor tissues. Conclusion: This study established that COPA outperforms AFP and PIVKAII in diagnostic and immunotherapeutic monitoring reliability, offering a novel technique for the precise diagnosis and treatment of hepatocellular carcinoma.

Background: The immunoregulatory cytokine interleukin (IL)-35 has been implicated in the pathogenesis of hepatocellular carcinoma (HCC). Here, we explored the association between single-nucleotide polymorphisms (SNPs) in the IL-35 gene and the occurrence of HCC in patients with chronic hepatitis B virus (HBV). Methods: We selected 39 patients with chronic hepatitis B (HBV) and 52 patients with HBV-related hepatocellular carcinoma (HCC) as the case groups, along with 42 healthy individuals as the control group. We genotyped five IL-35-related single-nucleotide polymorphisms (SNPs) and analyzed their association with HCC risk. In addition, serum IL-35 levels, lymphocyte counts, and regulatory T cell (Treg) frequencies were measured in peripheral blood across all groups. Results: The frequency of the rs583911 AA genotype tended to increase from healthy controls (4.8%) to patients with chronic HBV (10.3%) to patients with HCC (21.2%) (P for trend = 0.03). When patients with HCC were compared to non-HCC controls (healthy controls + chronic HBV carriers), the rs583911 AA genotype was associated with HCC risk (OR = 3.35; 95% CI: 1.17–9.61, P = 0.020). After adjusting for age, sex, cirrhosis status, and antiviral therapy, the association was no longer statistically significant (adjusted P = 0.085). Serum IL-35 levels were significantly elevated in both the HBV and the HCC groups compared with those in the control group ( P < 0.001), with no significant difference between the HBV and the HCC groups ( P = 0.434). Within the HCC subgroup, patients with the AA genotype tended to have higher IL-35 levels ( P = 0.047). Flow cytometry analysis of a subset of samples (6 controls, 6 patients with HBV, and 28 patients with HCC) revealed that the number of Treg cells was greater in patients with HCC than in those with HBV ( P = 0.038). Conclusion: Our findings suggest a potential association between the rs583911 AA genotype and HBV-related HCC risk. However, these exploratory findings did not remain statistically significant after rigorous adjustment for multiple comparisons and potential confounders; therefore, validation in larger, independent cohorts is needed.

Esophageal squamous cell carcinoma (ESCC) remains a lethal malignancy with a poor 5-year survival rate of approximately 20%, necessitating the identification of novel therapeutic targets. Here, we show that KDM4A is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and its high expression correlates with poor prognosis. Functional assays demonstrated that KDM4A promotes ESCC cell proliferation, migration, invasion, and tumor growth in vitro and in vivo. Mechanistically, KDM4A demethylates H3K9me3 at the LRG1 promoter, thereby enhancing LRG1 transcription and activating the TGF-β pathway to drive epithelial-mesenchymal transition (EMT) and cancer stemness. Knockdown of KDM4A or LRG1 suppresses these oncogenic phenotypes, while LRG1 overexpression rescues KDM4A deficiency–induced impairments. Clinically, KDM4A and LRG1 are co-overexpressed in ESCC tissues and associated with advanced tumor stage and shorter overall survival. These findings identify the KDM4A–LRG1–TGF-β axis as a critical driver of ESCC progression and a potential therapeutic target.

Objective: The main objective of this study is to investigate the prognostic value of serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) in predicting postoperative outcomes for hepatocellular carcinoma (HCC) patients after surgical resection. Methods: Serum PIVKA‑II levels were compared between early‑stage (stage I+II) and advanced‑stage (stage III+IV) HCC patients. Correlations between PIVKA‑II and clinicopathological features were examined. Kaplan‑Meier curves were plotted to assess overall survival (OS) and recurrence‑free survival (RFS) by PIVKA‑II levels. Receiver operating characteristic (ROC) analysis compared the predictive performance of PIVKA‑II and α ‑fetoprotein (AFP), with DeLong ’s test evaluating differences in area under the curve. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors for postoperative survival and recurrence. Results: Serum PIVKA‑II levels were significantly elevated in HCC patients compared with controls ( P < 0.01), and were higher in advanced‑stage than early‑stage HCC ( P < 0.01). PIVKA‑II correlated significantly with tumor diameter, tumor node metastasis classification, lymph node infiltration, distant metastasis, differentiation, and complication incidence (all P < 0.05). Patients with high PIVKA‑II (≥100 mAU/ml) had shorter median OS and RFS than those with low levels (P < 0.01). PIVKA‑II outperformed AFP in predicting 5‑year survival and recurrence ( P < 0.05), and combined use improved predictive accuracy ( P < 0.05). Multivariate Cox regression identified PIVKA‑II ≥100 mAU/ml as an independent prognostic factor for both OS and RFS ( P < 0.05). Conclusion: Our study confirms that serum PIVKA-II can serve as a prognostic predictor for HCC patients after surgical treatment.

Human epidermal growth factor receptor 2 (HER2) is a critical biomarker for targeted therapy of gastric cancer. Tissue‐based HER2 testing via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) remains the clinical gold standard, while serum HER2 represents a potential complementary circulating biomarker for disease monitoring. However, conventional serum HER2 assays often suffer from limited sensitivity. Herein, we develop a highly sensitive fluorescence assay for serum HER2 detection using nonlinear hybridization chain reaction (NHCR) coupled with a HER2‐specific aptamer (HB5). Unlike linear hybridization chain reaction (HCR), NHCR enables branching‐mediated exponential amplification, in which each trigger initiates multiple independent HCR cascades, leading to nonlinear signal growth. The method exhibited a good linear relationship ( R ² = 0.993) in the HER2 concentration range of 0.5–90 ng·mL ⁻¹ , with a detection limit as low as 38 pg·mL ⁻¹ . The sensor demonstrated excellent specificity for HER2, good reproducibility, and reliable stability. Clinical serum sample detection results indicated that the method was highly correlated with the clinically commonly used chemiluminescence immunoassay (CLIA), with spiked recoveries ranging from 95.4% to 109.6%. The NHCR‐based fluorescent detection strategy established in this study provides a new tool for accurate and noninvasive detection of serum HER2, featuring simple operation and controllable cost.

Background/Aims: Hepatocellular carcinoma (HCC) constitutes approximately 85% of liver cancers. This study aimed to investigate the role of immune escape-related genes (IEGs) in HCC patients and analyze their relationship with prognosis and immunotherapy, thereby providing a reference for further clinical treatment. Materials and Methods: Datasets were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Differential expression analysis was conducted to identify differentially expressed IEGs between normal and HCC tissues. Expression, survival, mutational, and immune profiles of a hub gene nuclear transport factor 2 like export factor 1 (NXT1) were evaluated. Validation of NXT1 expression in adjacent normal and HCC tissues was carried out using RT-qPCR and western blot assays. Next, CCK-8, wound healing, and transwell assays were conducted to evaluate the biological function of NXT1 in HCC cell lines. Results: Analysis of the TCGA-LIHC and GSE164359 datasets revealed that NXT1 was notably elevated in HCC tissues compared to adjacent normal tissues, a finding validated through RT-qPCR and western blot assays. Meanwhile, high levels of NXT1 were associ ated with an unfavorable prognosis of HCC patients. Mutational analysis indicated a higher incidence of TP53 mutations in the NXT1 high-expression group relative to the NXT1 low-expression group. HCC patients with high NXT1 expression demonstrated an increased proportion of M0 macrophages and regulatory T cells (Tregs) and a decreased proportion of M1 macrophages. Furthermore, deficiency of NXT1 significantly suppressed HCC cell viability, migration, and invasion. Conclusion: Collectively, NXT1 may serve as a valuable prognostic marker and a potential therapeutic target for HCC. Cite this article as: Guo J, Tong X, Liu S, et al. Immune escape-related gene NXT1 as a potential prognostic and therapeutic target in hepatocellular carcinoma. Turk J Gastroenterol. Published online August 25, 2025. doi 10.5152/tjg.2025.24193.

β-Hydroxybutyrylation (Kbhb) modification regulates protein molecular fates in either physiology or pathology, including cancer. However, the function and regulatory mechanism of Kbhb remain completely unknown in cancer metastasis. Here, we report that β-hydroxybutyrate (BHB) is clinically associated with the progression of pancreatic cancer and functionally promotes pancreatic cancer cell metastasis. Mechanistically, BHB induces Kbhb modification of Snail at lysine 152 to enhance Snail stabilization, which is regulated by Kbhb modification enzyme CREB-binding protein (CBP), and subsequently prevents Snail degradation by blocking recognition of E3 ubiquitin ligases FBXL14. Furthermore, either targeting Snail Kbhb modification or CBP inhibitor decreases cancer metastasis and enhances the therapeutic efficacy of gemcitabine in pancreatic cancer cells. Collectively, our study reveals that Kbhb of Snail is critical to promote metastasis and provides a potential therapeutic strategy.

Background: An elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been reported to be a negative prognostic marker in many types of cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether NLR is associated with the tumor-immune microenvironment (TIME) in PDAC is unclear. Understanding the interplay between systemic inflammation as reflected by NLR and TIME in PDAC is crucial for identifying prognostic biomarkers and potential therapeutic targets. The aim of this study was to examine the relationship between the NLR and clinical outcomes in patients with early-stage PDAC and the impact of the TIME in PDAC. Methods: We conducted a retrospective analysis including two cohorts: PDAC patients versus healthy controls and untreated stage I–II PDAC cases. We collected clinical data, including NLR values and followed PDAC patients for overall survival (OS) and relapse-free survival (RFS), and the TIME was evaluated through immunohistochemical staining for CD8⁺ T cells and CD33⁺ myeloid-derived suppressor cells (MDSCs). Statistical analyses were performed to assess the relationship between NLR, clinical outcomes, and TIME components to further determine the value of NLR in reflecting the status of the TIME and predicting outcomes of patients with PDAC. Results: NLR was negatively associated with OS and RFS in patients with PDAC. Moreover, NLR was found to be a prognostic factor for PDAC and early-stage PDAC. The NLR was inversely correlated with the abundance of tumoral CD8⁺ T cells (r=−0.345, P=0.004) and positively correlated with that of CD33⁺ MDSCs (r=0.407, P=0.001). Conclusions: Our findings indicate that a high NLR value is closely correlated with poor outcomes in patients with PDAC. In addition, it was significantly associated with the presence of tumoral CD8⁺ tumor-infiltrating lymphocytes and CD33⁺ cells in the TIME of patients with PDAC. NLR may be a biomarker that can inform treat-related decision-making.

Original Article Fructose-diphosphate aldolase C as a novel diagnostic biomarker for early-stage non-small cell lung cancer: a low-abundance proteomics study Changsen Bai, Qianhui Hao, Yunxiang Chen, Jiayi Wang, Jiawei Xiao, Da Hyun Kang, Li Ren