Alteration of tumor suppressor gene p16 and Rb in gastric cancinogesis

IM To study the alterations of tumor suppressor gene p16 and Rb in the carcinogenesis of the stomach. METHODS Different mucosal biopsies were endoscopically obtained, all samples were immediately fixed with 10% buffered formalin, embedded with paraffin and sectioned serielly. Alterations of p16 and Rb protein in 12 cases of superficial gastritis, 15 atrophic gastritis, 20 atypical hyperplasia and 40 cancerous tissues were detected by the immunohistochemical method (ABC). RESULTS Different degrees of nuclear immunostaining of p16 and Rb occurred on gastric epithelium in different stages of lesions. With the lesions progressing, the positive immunostaining rate of p16 protein had a decreasing tendency (833%→733%→300%→275%), and on the other hand, that of Rb protein had an increasing tendency (250%→467%→600%→675%). A negative correlationship was found between these two parameters in the gastric cancer. Of 40 cases of gastric cancer, a negative relationship was observed in 20 cases. In comparison with both positive (9 cases) and both negative tissues (11 cases), there was a significant difference (500%,225%,275%) (P<005).CONCLUSION Abnormal expression of p16 and Rb plays an important role in gastric carcinogenesis.

In situ detection of tumor infiltrating lymphocytes expressing perforin and fas-ligand genes in human HCC

AIM To investigate the expression of perforin and fas ligand (fas L) of tumor infiltrating lymphocytes (TILs) in human hepatocellular carcinoma (HCC). METHODS By in situ hybridization and immunohistochemistry, the perforin and fas L gene expression of TILs was studied in 20 HCC cases. RESULTS Positive expression of perforin and fas L genes was detected in 16 HCC cases. One patient had expression of perforin and fas L genes in the majority of TILs and survived 1 5 years after tumor resection without HCC relapse. This seems that the presence of a large number of activated T cells might be beneficial for the antitumor immunity. In other cases, less than 10% of TILs were able to express perforin and fas L genes. CONCLUSION Although there were a number of T cells in HCC, only few of them were immunoactive and able to kill tumor cells. It seems important to promote further proliferation of these activated T cells in vitro or in vivo .

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

THE THERAPEUTIC EFFECT OF INTRATUMORAL INJECTION OF GM-CSF GENE-MODIFIED ALLOGENIC MACROPHAGES ON TUMOR-BEARING MICE

Both the antigen presenting ability and the cytotoxicity of macrophages can be enhanced by GMCSF gene transfer. In the present study, the therapeutic effect of intratumoral injection with GMCSF genemodified allogenic macrophages on tumorbearing mice observed. The peritoneal macrophages of C57BL/6 mice were transfected with GMCSF gene mediated by recombinant adenovirus and the subcutaneous CT26 colon adenocarcinomabearing BALB/c mice were treated by intratumoral injection of the above macrophages. The survival time of the tumorbearing mice were prolonged significantly and some tumor mass disappeared completely. The necroses of the tumor cells and massive infiltration of inflammatory cells were observed 6 days after treatment. 30 days after treatment, only the leftover of tumor cells and the inflammatory cells remained. The data indicated that introtumoral injection of GMCSF genemodified allogenic macrophages displayed more potent therapeutic effect on the preestablished tumorbearing mice.

ANTITUMOR EFFECT OF INTRATUMORAL INJECTION OF LIPOSOME-ENCAPSULATED G-CSF GENE AND IN SITU BIOLOGICAL CHARACTERISTICS OF THE TREATED TUMOR CELLS

This word was supported by grant from Military Medical Research Foundation of china (96z032). ** To whom correspondence and requests for reprints should be addressed. This is one of papers of the special issue on gene therapy research (Chin J Cancer Res Vol. 9 No. 4 December, 1997). In order to investigate the antitumor effects of the in vivo G CSF gene therapy mediated by liposome and its mechanisms, human G CSF gene was encapsulated into liposome and was directly injected into tumor mass of C 26 colon adenocarcinoma bearing mice. After direct intratumoral injection of liposome encapsulated G CSF DNA, the subcutaneous tumor growth was dramatically inhibited and the survival time was prolonged signifi cantly. Tumor regression could be observed in about 30% of C 26 bearing mice. By the analysis of the antitumor mechanisms, we found that anti G 418 (600ug/ml) clone could be selected from the tumor cells freshly separated from the treated C 26 tumor mass, and secretion of G CSF in the supernatant could be detected. Northern blot also confirmed the expression of hG CSF by the tumor cells. Higher expressions of MHC class I(H 2k d) molecule and ICAM 1 on the tumor cells could be observed. The results demonstrated that liposome can effectively transfect G CSF gene into tumor cells in situ , and then increase the immunogenicity of the tumor cells which may contribute to the activation of the local antitumor immune responses effectively.

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

RFLP Analysis of Nov Gene in Tumor and Normal Cells

Using human nov (nephroblastoma overexpressed,nov) DNA as probe,hybridization to total cellular DNAs of tumor and normal cells digested by restriction enzymes BamHI or EcoRI respectively was carried out through Southern blot. It was observed that nov gene in these cells is not only highly conserved, but also certains RFLP characteristic . The correlation between RFLP characteristic of nov gene and its function was analyzed .

N6-methyladenosine methyltransferase Wilms tumor 1-associated protein impedes diabetic wound healing through epigenetically activating DNA methyltransferase 1

BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes.N6-methyladenosine(m6A)-related epigenetic regulation is widely involved in the pathogenesis of diabetes complications.However,the function of m6A methyltransferase Wilms tumor 1-associated protein(WTAP)in diabetic wound healing remains elusive.AIM To investigate the potential epigenetic regulatory mechanism of WTAP during diabetic wound healing.METHODS Human umbilical vein endothelial cells(HUVECs)were induced with high glucose(HG)to establish in vitro cell model.Male BALB/c mice were intraperitoneally injected with streptozotocin to mimic diabetes,and full-thickness excision was made to mimic diabetic wound healing.HG-induced HUVECs and mouse models were treated with WTAP siRNAs and DNA methyltransferase 1(DNMT1)overexpression vectors.Cell viability and migration ability were detected by cell counting kit-8 and Transwell assays.In vitro angiogenesis was measured using a tube formation experiment.The images of wounds were captured,and re-epithelialization and collagen deposition of skin tissues were analyzed using hematoxylin and eosin staining and Masson’s trichrome staining.RESULTS The expression of several m6A methyltransferases,including METTL3,METTL14,METTL16,KIAA1429,WTAP,and RBM15,were measured.WTAP exhibited the most significant elevation in HG-induced HUVECs compared with the normal control.WTAP depletion notably restored cell viability and enhanced tube formation ability and migration of HUVECs suppressed by HG.The unclosed wound area of mice was smaller in WTAP knockdowntreated mice than in control mice at nine days post-wounding,along with enhanced re-epithelialization rate and collagen deposition.The m6A levels on DNMT1 mRNA in HUVECs were repressed by WTAP knockdown in HUVECs.The mRNA levels and expression of DNMT1 were inhibited by WTAP depletion in HUVECs.Overexpression of DNMT1 in HUVECs notably reversed the effects of WTAP depletion on HG-induced HUVECs.CONCLUSION WTAP expression is elevated in HG-induced HUVECs and epigenetically regulates the m6A modification of DNMT1 to impair diabetic wound healing.

Genetic insights in infectious diseases:Insights from a case report and implications for personalized medicine

The relationship between genetics and infectious diseases is important in shaping our understanding of disease susceptibility,progression,and treatment.Recent research shows the impact of genetic variations,such as heme-oxygenase promoter length,on diseases like malaria and sepsis,revealing both protective and inconclusive effects.Studies on vaccine responses highlight genetic markers like human leukocyte antigens,emphasizing the potential for personalized immunization strategies.The ongoing battle against drug-resistant tuberculosis(TB)illustrates the complexity of genomic variants in predicting resistance,highlighting the need for integrated diagnostic tools.Additionally,genome-wide association studies reveal antibiotic resistance mechanisms in bacterial genomes,while host genetic polymorphisms,such as those in solute carrier family 11 member 1 and vitamin D receptor,demonstrate their role in TB susceptibility.Advanced techniques like metagenomic next-generation sequencing promise detailed pathogen detection but face challenges in cost and accessibility.A case report involving a highly virulent Mycobacterium TB strain with the pks1 gene further highlights the need for genetic insights in understanding disease severity and developing targeted interventions.This evolving landscape emphasizes the role of genetics in infectious diseases,while also addressing the need for standardized studies and accessible technologies.

Dystrophic epidermolysis bullosa caused by novel frameshift mutation in the COL7A1 gene: A case report

BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。

Resolving tumor evolution:a phylogenetic approach

The evolutionary dynamics of cancer,characterized by its profound heterogeneity,demand sophisticated tools for a holistic understanding.This review delves into tumor phylogenetics,an essential approach bridging evolu-tionary biology with oncology,offering unparalleled insights into cancer’s evolutionary trajectory.We provide an overview of the workflow,encompassing study design,data acquisition,and phylogeny reconstruction.No-tably,the integration of diverse data sets emerges as a transformative step,enhancing the depth and breadth of evolutionary insights.With this integrated perspective,tumor phylogenetics stands poised to redefine our understanding of cancer evolution and influence therapeutic strategies.

Bidirectional regulation of the cyclic guanosine monophosphateadenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are limited.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)activates the stimulator of interferon gene(STING)signaling pathway as a crucial immune response pathway in the cytoplasm,which detects cytoplasmic DNA to regulate innate and adaptive immune responses.As a potential therapeutic target,cGASSTING pathway markedly inhibits tumor cell proliferation and metastasis,with its activation being particularly relevant in HCC.However,prolonged pathway activation may lead to an immunosuppressive tumor microenvironment,which fostering the invasion or metastasis of liver tumor cells.AIM To investigate the dual-regulation mechanism of cGAS-STING in HCC.METHODS This review was conducted according to the PRISMA guidelines.The study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science databases.Through rigorous screening and meticulous analysis of the retrieved literature,the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC tumors.RESULTS All authors collaboratively selected studies for inclusion,extracted data,and the initial search of online databases yielded 1445 studies.After removing duplicates,remaining 964 records were screened.Ultimately,55 articles met the inclusion criteria and were included in this review.CONCLUSION Acute inflammation can have a few inhibitory effects on cancer,while chronic inflammation generally promotes its progression.Extended cGAS-STING pathway activation will result in a suppressive tumor microenvironment.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Pan-TRK positive uterine sarcoma in immunohistochemistry without neurotrophic tyrosine receptor kinase gene fusions:A case report

BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.

Reduction of tumorigenicity of SMMC-7721 hepatoma cells by vascular endothelial growth factor antisense gene therapy

AIM: To test the hypothesis to block VEGF expression of SMMC-7721 hepatoma cells may inhibit tumor growth using the rat hepatoma model. METHODS: Amplify the 200 VEGF cDNA fragment and insert it into human U6 gene cassette in the reverse orientation transcribing small antisense RNA which could specifically interact with VEGF165, and VEGF121 mRNA. Construct the retroviral vector containing this antisense VEGF U6 cassette and package the replication-deficient recombinant retrovirus. SMMC-7721 cells were transduced with these virus and positive clones were selected with G418. PCR and Southern blot analysis were performed to determine if U6 cassette integrated into the genomic DNA of positive clone. Transfected tumor cells were evaluated for RNA expression by ribonuclease protection assays. The VEGF protein in the supernatant of parental tumor cells and genetically modified tumor cells was determined with ELISA. In vitro and in vivo growth properties of antisense VEGF cell clone in nude mice were analyzed. RESULTS: Restriction enzyme digestion and PCR sequencing verified that the antisense VEGF RNA retroviral vector was successfully constructed.After G418 selection, resistant SMMC-7721 cell clone was picked up. PCR and Southern blot analysis suggested that U6 cassette was integrated into the cell genomic DNA. Stable SMMC-7721 cell clone transduced with U6 antisense RNA cassette could express 200 bp small antisense VEGF RNA and secrete reduced levels of VEGF in culture condition. Production of VEGF by antisense transgene-expressing cells was 65+/-10 ng/L per 10(6) cells, 42045 ng/L per 10(6) cells in sense group and 485+/-30 ng/L per 10(6) cells in the negative control group, (P【 0.05). The antisense-VEGF cell clone appeared phenotypically indistinguishable from SMMC-7721 cells and SMMC-7721 cells transfected sense VEGF. The growth rate of the antisense-VEGF cell clone was the same as the control cells. When S.C. was implanted into nude mice, growth of antisense-VEGF cell lines was greatly inhibited compared with control cells. CONCLUSION: Expression of antisense VEGF RNA in SMMC-7721 cells could decrease the tumorigenicity, and antisense-VEGF gene therapy may be an adjuvant treatment for hepatoma.

Genetic and epigenetic alterations associated with gestational diabetes mellitus and adverse neonatal outcomes

Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.

Autophagy-targeting modulation to promote peripheral nerve regeneration

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.