International Journal of Biological Markers最新文献

ObjectivesWe investigated the interactions among DHX9, phosphorylated DHX9, R-loops, and DNA damage to clarify the mechanism by which phosphorylated DHX9 inhibited lung adenocarcinoma progression.MethodsUsed PC-9 and 2BS cells divided into control, siDHX9, OE-DHX9, siDHX9 + OE-RNase H1, OE-PKA, DHX9-S279A, 6-22 Amide, and DHX9-S279A + OE-RNase H1 groups. Assays included quantitative real-time polymerase chain reaction (qRT-PCR), WB (DHX9, γH2AX, Rad51, pCtIP), EdU/CCK-8 (proliferation), TUNEL/flow cytometry (apoptosis), comet assay (DNA damage), CldU/IdU (replication), DRIP-qPCR (R-loops). Nude mice xenografts (control, siDHX9, DHX9-S279E, DHX9-S279A) assessed tumor growth, Ki67, R-loops, DNA damage, and replication.ResultsDHX9 was highly expressed in multiple cancer tissues and lung cancer cell lines, with higher messenger RNA levels in PC-9 than in 2BS cells. Compared with PC-9, siDHX9 reduced proliferation and increased apoptosis, while OE-DHX9 exerted opposite effects. siDHX9 increased DNA damage (with corresponding changes in γH2AX, Rad51, and pCtIP levels), reduced replication (rescued by OE-RNase H1), and elevated R-loops; OE-DHX9 showed opposite effects on damage and R-loops. OE-PKA increased R-loops and damage, and reduced replication, while DHX9-S279A or 6-22 Amide decreased these and 6-22 Amide also increased replication versus PC-9/OE-PKA. DHX9-S279A increased proliferation, with DHX9-S279A + OE-RNase H1 further enhancing this and reducing apoptosis. In vivo, siDHX9 and DHX9-S279E reduced tumor volume/mass and Ki67, increased R-loops, damage, and γH2AX/Rad51/pCtIP, and inhibited replication; DHX9-S279A showed opposite effects versus these groups, with no significant tumor difference versus PC-9 and higher replication versus both.ConclusionsPhosphorylated DHX9 might enhance DNA damage by suppressing R-loop resolution, ultimately inhibiting the proliferation of lung adenocarcinoma cells.

The global incidence of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) has increased markedly over recent decades, leading to a fundamental shift in the epidemiology and clinical management of head and neck malignancies. HPV-positive HNSCC represents a biologically and clinically distinct disease entity, characterized by unique molecular features, improved treatment responsiveness, and a more favorable prognosis compared with HPV-negative tumors. However, the optimal integration of molecular insights with evolving therapeutic strategies remains an ongoing clinical and translational challenge. In this review, we summarize the etiological role of HPV in the pathogenesis of HNSCC and delineate key differences in epidemiology, molecular biology, and clinical presentation between HPV-positive and HPV-negative disease. We further examine current standard-of-care treatments, including surgery, radiotherapy, and chemotherapy, with particular emphasis on de-escalation strategies aimed at reducing long-term toxicity while maintaining oncologic efficacy in HPV-positive patients. Emerging immunotherapeutic approaches have demonstrated encouraging activity in recurrent or metastatic disease. Moreover, therapeutic vaccine development, including DNA-, mRNA-, peptide-, and viral vector-based platforms targeting HPV E6/E7 oncoproteins, represents a rapidly evolving area with the potential to enhance antitumor immunity. This review also highlights ongoing clinical trials that may reshape the future landscape of treatment for HPV-positive HNSCC. Collectively, these advances emphasize the importance of HPV status in guiding personalized management strategies and improving patient outcomes.

IntroductionCervical cancer represents a significant global health problem, ranking as the fourth most prevalent malignant cancer in women, particularly in low- and middle-income countries. Epigenetic silencing via aberrant methylation of tumor suppressor genes' promoters represent a second hit of cancer initializing, as well as progressing. The aim of current meta-analysis was to systematically evaluate the potential of DNA methylation-based biomarkers in non-invasive or minimal invasive samples using molecular-based approaches for cervical cancer screening and diagnosis.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was applied to perform our meta-analysis. The frequency, odds ratios, sensitivity as well as specificity with the corresponding 95% confidence intervals were used to assess the effect sizes.ResultsThere were 20 eligible articles ultimately included in the current meta-analysis. In this meta-analysis, multiple tumor suppressor genes, such as, especially, PAX1, SOX1, CDO1, GHSR, were shown to undergo hypermethylation in cervical cancer samples compared with controls. Urine samples, when combined with MSP- and qMSP-based approaches, emerged as a particularly effective non-invasive strategy.ConclusionThe current meta-analysis highlighted the important steps toward establishing DNA-methylation-based biomarkers as accessible and reliable tools for CC screening and diagnosis.

ObjectivesTo explore the causal associations between oxidative stress markers and the occurrence of various types of lymphomas.MethodsThis two-sample Mendelian randomization (MR) study employed summary data from genome-wide association studies of oxidative stress markers and various lymphoma types. Analysis was conducted using the inverse variance weighted, with confirmation using the weighted median, weighted mode, and MR-Egger regression methods. Heterogeneity, horizontal pleiotropy, outliers, and robustness were tested using the Cochran Q, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods.ResultsGenetically predicted myeloperoxidase (MPO) was causally associated with follicular lymphoma (odds ratio (OR) = 1.33, P = 0.0173). Uric acid showed a causal link to diffuse large B-cell lymphoma (DLBCL) (OR = 1.003, P = 0.043). Glutathione peroxidase (GPX) was associated with follicular lymphoma (OR = 1.16, P = 0.033). Catalase (CAT) was inversely associated with non-Hodgkin lymphoma (NHL) (OR = 0.8921), non-follicular lymphoma (OR = 0.8755), and follicular lymphoma (OR = 0.8364) (all P < 0.05). Glutathione-S transferase (GST) was inversely associated with NHL (OR = 0.9248) and follicular lymphoma (OR = 0.8313) (all P < 0.05). Heterogeneity was noted for uric acid and DLBCL, but no pleiotropy was detected; after outlier removal, the association with uric acid was non-significant.ConclusionsThe findings suggest causal relationships between oxidative stress markers and lymphoma risk, notably MPO and GPX with follicular lymphoma, and inverse associations for GST and CAT with different lymphoma types. Limitations include heterogeneity for some markers, requiring further validation.

BackgroundLung adenocarcinoma (LUAD) remains one of the leading causes of cancer-related deaths worldwide, with limited therapeutic efficacy despite advances in treatment. Our study investigated the role of LINC00578 and its regulatory interaction with miR-153-5p in LUAD progression.MethodsThe expression levels of LINC00578 and miR-153-5p were assessed in LUAD tissues and adjacent normal tissues using quantitative real-time polymerase chain reaction. Associations between LINC00578 expression and clinicopathological features and patient prognosis were analyzed. Luciferase reporter assays, proliferation, migration, invasion, and apoptosis analyses, were conducted in LUAD cell lines (PC-9 and H1299) following modulation of LINC00578 and miR-153-5p expression.ResultsLINC00578 was significantly upregulated in LUAD tissues compared to adjacent normal tissues, whereas miR-153-5p was markedly downregulated. High LINC00578 expression was associated with lymph node metastasis, tumor-node-metastasis stage, and poor overall survival. Functional studies revealed that silencing LINC00578 inhibited LUAD cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, LINC00578 exerted its oncogenic effects by negatively regulating miR-153-5p expression. Inhibition of miR-153-5p reversed the tumor-suppressive effects induced by LINC00578 knockdown.ConclusionLINC00578 functions as an oncogenic long non-coding RNA in LUAD by promoting proliferation and metastasis through suppression of miR-153-5p. LINC00578 may serve as a novel prognostic biomarker for LUAD.

Progress in precision oncology depends on effective and well-coordinated collaboration between pre-clinical researchers and clinical investigators. In this setting, the European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology group (PBG) plays a key role in reinforcing the link between biological research and clinical investigation, facilitating the translation of biological and medical findings into clinical application, supporting the rigorous testing of molecular hypotheses in clinical trials, and providing multidisciplinary expertise for biomarker development and validation across different tumor types. A defining characteristic of the EORTC PBG is its pan-tumor perspective, which is consistent with the evolving molecular taxonomy of cancer and, through specialized expertise in molecular biology, pathology, biomarker development, and quality assurance, contributes to the activities of both the EORTC Translational Research Division and the Disease-Oriented Groups. This editorial outlines the scientific mission and achievements of the EORTC PBG, highlights the increasing contribution of Young and Early Career Investigators within the group, and emphasizes the importance of pathobiology-driven research in rare cancers, where unmet clinical needs remain considerable.

PurposeThis study aimed to investigate KRAB-associated protein 1 (KAP1) expression in pleural mesothelioma (PM) and its impact on the biological behavior of the human pleural mesothelioma cell line MSTO-211H, providing a specific biomarker for the early clinical diagnosis of PM.Patients and methodsKAP1 expression levels in PM tissues were detected using immunohistochemistry. Lentivirus infection was used to construct MSTO-211H mesothelioma cell lines with stable KAP1 overexpression or knockdown, and the efficiency of KAP1 overexpression or knockdown was detected using qRT-PCR(quantitative Reverse Transcription PCR) and Western blotting. The effects of KAP1 overexpression and knockdown on MSTO-211H mesothelioma cell proliferation, migration, and invasion were detected using cell counting kit-8, plate colony formation, cell scratch, and transwell invasion assays, respectively. The effects of KAP1 overexpression and knockdown on the cell cycle, related cyclins, and apoptosis were detected using flow cytometry. Gene enrichment and correlation analysis of mesothelioma were performed using bioinformatics analysis.ResultsKAP1 was significantly overexpressed in PM tissues compared with normal pleural tissues (P < 0.05). Compared to the control group, KAP1 overexpression in mesothelioma MSTO-211H cells significantly enhanced proliferation, migration, and invasion (P < 0.05), without causing cell cycle arrest, and significantly increased the mRNA and protein levels of cyclin D1 and cyclin E (P < 0.05), whereas the apoptosis rate did not significantly change (P > 0.05). Conversely, KAP1 knockdown in mesothelioma MSTO-211H cells significantly inhibited their proliferation, migration, and invasion abilities (P < 0.05), induced G0/G1 phase arrest in the cell cycle, and significantly increased the apoptosis rate (P < 0.05). Spearman correlation analysis revealed significant positive associations between KAP1 mRNA expression and TP53 and SHOX2. Conversely, KAP1 expression was significantly negatively correlated with MTAP and MSLN. GSEA reveals KAP1-associated enrichment of DNA repair, cell cycle, and proteostasis pathways in TCGA-MESO.ConclusionKAP1 is highly expressed in PM and functions as an oncogene-like regulator, enhancing tumor cell growth and aggressiveness.Clinical trial registration2023-28.

BackgroundEsophageal cancer is an aggressive malignant tumor, and its incidence rate is constantly increasing. Searching for a new biomarker is essential for the study of esophageal cancer.MethodsThe microRNA and messengerRNA expression levels were measured by employing RT-qPCR. The diagnostic value of miR-1303 in esophageal cancer was measured by the receiver operating characteristic curve. In TE-1 cells and KYSE520 cells, miR-1303 and CLDN18 were overexpressed or inhibited by transfection. The target of miR-1303 was forecasted by the TargetScan online database, which was identified by the dual-luciferase reporter system. The correlation between miR-1303 and CLDN18 in esophageal cancer was analyzed.ResultsMiR-1303 in esophageal cancer tissues increased and had a high diagnostic value in esophageal cancer. In TE-1 cells and KYSE520 cells, the overexpression of miR-1303 increased the proliferation and decreased the apoptosis, and the inhibition of miR-1303 decreased the proliferation and increased the apoptosis. The overexpression of miR-1303 significantly increased MMP2 and MMP9 and decreased E-cadherin in TE-1 cells and KYSE520 cells, and the inhibition of miR-1303 decreased MMP2 and MMP9 and elevated E-cadherin in TE-1 cells and KYSE520 cells. In esophageal cancer tissues, the expression of CLDN18 was significantly reduced, and CLDN18 was negatively correlated with miR-1303. In TE-1 cells and KYSE520 cells, the up-regulation of CLDN18 alleviated the progression of esophageal cancer caused by miR-1303.ConclusionMiR-1303 was increased in esophageal cancer tissue and had a high diagnostic value in esophageal cancer. MiR-1303 promoted the invasion and metastasis of esophageal cancer. In esophageal cancer, the inhibition of miR-1303 suppressed the development by targeting CLDN18.

Increasing evidence showed that altered histone deacetylases (HDACs) are involved in, and exert cell type specific roles in sarcomagenesis. Here we reviewed expression and roles of HDACs in several types of human sarcomas, providing a basic guideline for personalized therapy. In sarcomas, overexpression of HDACs was common, including a prevalence in uterine sarcomas. Class I HDAC1-3, especially HDAC1-2, were upregulated in most sarcomas and were often associated with poor prognosis. Class I HDACs inhibit tumor suppressor expression and lineage differentiation, but maintain chromatin integrity and oncofusion protein stability. Class II HDACs have specific functions in cellular transformation, long telomeres maintenance, drug resistance, and cytoskeletal organization, and act as negative predictors in some sarcomas; for example, HDAC4 for leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS), HDAC5 for uterine LMS, HDAC6 for ESS, chondrosarcoma (CHS) and undifferentiated endometrial sarcoma. Moreover, some HDACs play dual, cell-context or cellular localization-dependent roles. HDAC2 and HDAC5 could promote or suppress osteosarcoma growth. HDAC4 acts as a tumor suppressor in CHS but as an oncogene in other sarcomas. Moreover, HDAC4 is the targets of several microRNAs in osteosarcoma. Cytoplasmic HDAC6 increases self-renewal and cell migration, compared with nuclear HDAC6 enhancing EWSR1-FLI1 transcription. Thus, the diverse expression and roles of HDACs in sarcoma pathogenesis will be a solid foundation to guide personalized therapeutic application of HDAC modulators in sarcomas.

BackgroundThe Cancer Genome Atlas (TCGA) molecular classification has advanced risk stratification for endometrial carcinoma but has demonstrated comparable survival outcomes between the microsatellite instability (MSI) and copy-number low (CN-L) subtypes. In this study, we aimed to identify potential autophagy-related molecular signatures to increase the precision of TCGA-based prognostic stratification in early-stage endometrial carcinoma.MethodsUnivariate Cox regression analysis of the TCGA-Uterine Corpus Endometrial Carcinoma cohort was used to identify autophagy-related genes associated with survival outcomes in patients with endometrial carcinoma. The candidates were analyzed by the Kaplan-Meier method. Multivariate Cox regression was used to assess whether PEA15 served as an independent prognostic factor, especially for the MSI and CN-L subtypes. We examined the correlation between PEA15 protein expression and patient survival through immunohistochemical analysis of tissue microarrays from our institutional cohort of stage I endometrial cancer patients.ResultsUnivariate analysis revealed that NRG3, PEA15, DNAJB1, BAK1, DRAM1, KLHL24, ATF6, CDKN2A, MBTPS2, and UVRAG were significantly associated with survival outcomes in early-stage endometrial carcinoma patients. Multivariate analysis established PEA15 as an independent prognostic factor. Immunohistochemical analysis of tissue microarrays revealed that elevated PEA15 expression was significantly correlated with poorer overall survival and disease-free survival. Both univariate and multivariate Cox regression confirmed high PEA15 expression as an independent prognostic factor for recurrence in patients with stage I endometrioid adenocarcinoma.ConclusionsThe autophagy-related gene PEA15 is an independent prognostic biomarker in early-stage endometrial carcinoma, improving risk stratification between the MSI and CN-L subtypes. Immunohistochemical detection has clinical potential for molecular classification, offering opportunities for personalized postoperative management strategies.