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PubMed1996

Cost of treating advanced colorectal cancer: a retrospective comparison of treatment regimens.

Introduction of new agents on to hospital drug formularies requires the demonstration of efficacy, safety and cost advantages. An audit of the total monthly costs of 'Tomudex' (raltitrexed; administered every 3 weeks), a drug recently introduced for the treatment of advanced colorectal cancer, and three 5-fluorouracil-based regimens [5-day daily bolus (Mayo); continuous ambulatory pump; 48-h continuous infusion (De Gramont)] was undertaken. Patient-specific costs associated with fluids, concomitant medication and consumables were largely negligible, but chemotherapy was the main cost driver in the raltitrexed and De Gramont groups. Fixed inpatient costs were highest for the patients receiving the De Gramont regimen which required more impatient stays each month. Total costs (patient-specific plus fixed costs) were lowest in patients on the Mayo regimen (mean 954.03 Pounds; median 659.68 Pounds), followed by patients in the ambulatory pump (mean 1207.61 Pounds; median 749.19 Pounds), raltitrexed [mean 1256.93 Pounds; median 1087.14 Pounds (mean 1117.85 Pounds; median 959.34 Pounds when costs of protocol-driven visits were excluded)], and De Gramont groups (mean 2028.52 Pounds; median 1775.66 Pounds). The pattern of costs varied considerably between regimens, such that high drug costs, for example those associated with raltitrexed therapy, were partially offset by reductions in hospital visits and stays.

Adult↗

PubMed2026

Comprehensive Multiplatform Tyrosine Kinase Profiling Reveals Novel Actionable FGFR Aberrations across Sarcomas Affecting the Young.

Limited targeted agents are approved for pediatric sarcomas. Tyrosine kinase (TK) inhibitors (TKi) have shown clinical efficacy in some, but not all, young patients with sarcoma. A major obstacle preventing further advances and clinical implementation is the lack of predictive response biomarkers to guide TK-targeted treatments. TK-activating fusions or mutations are rare in these patients. RNA overexpression of TKs is a frequent feature. The unresolved question is when upregulated TK expression is associated with kinase activation and signaling dependence. We explored the TK molecular landscape of 107 patients with sarcoma from the ZERO Childhood Cancer Precision Medicine Program (ZERO) using whole-genome and -transcriptome sequencing. Phosphoproteomic analyses of tyrosine phosphorylation (pY) and functional in vitro and in vivo assays were performed in cell lines and patient-derived xenografts (PDX). Our analysis shows that although novel genomic driver lesions are rare, when present they are therapeutically actionable as exemplified by a novel LSM1-FGFR1 fusion identified in a patient with osteosarcoma. We further show that in certain contexts, TK RNA expression can indicate TK pathway activity and predict TKi sensitivity. We highlight the utility of FGFR inhibitors in PAX3-FOXO1 fusion-positive rhabdomyosarcomas (FP-RMS) characterized by high FGFR4 and FGF8 RNA expression levels and FGFR4 activation (FGFR4_pY). We demonstrate marked tumor growth inhibition in all FP-RMS PDXs treated with single-agent FGF401 (FGFR4-specific inhibitor) and single-agent lenvatinib (multikinase FGFR inhibitor) and report a clinical response to lenvatinib in a patient with relapsed metastatic FP-RMS. Altogether, we identified new patients with sarcoma who may benefit from FGFR inhibitors, most notably FP-RMS via FGFR4/FGF8 coexpression.

Journal Article↗

PubMed2026

Genetic and clinical insights into the coexistence of multiple myeloma and diffuse large B cell lymphoma from a case report and systematic review with bioinformatics analysis.

BACKGROUND: Multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL) are B-cell malignancies that rarely coexist in a single patient, presenting significant diagnostic and therapeutic challenges. While MM primarily involves clonal plasma cells, DLBCL is an aggressive lymphoid neoplasm. Investigating shared genetic mutations and understanding their clinical relevance in both cancers could provide novel insights into their pathogenesis and underlying molecular mechanisms, thereby informing future translational research. MATERIALS AND METHODS: A case report was conducted on a 52-year-old male who presented with abdominal pain and anemia. Imaging revealed lymphadenopathy, and biopsy confirmed high-grade DLBCL with concurrent bone marrow involvement suggestive of MM. Laboratory tests identified monoclonal IgM gammopathy, and the patient was treated with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) chemotherapy for DLBCL followed by autologous stem cell transplantation (ASCT) for MM relapse. A systematic review of the literature was performed using PubMed, Scopus, and Web of Science databases to identify cases of patients diagnosed with both MM and DLBCL. Data on patient demographics, clinical features, treatment regimens, and outcomes were extracted. Additionally, bioinformatics analysis was conducted using publicly available genomic data from cBioPortal and IntOGen to identify driver gene mutations in MM and DLBCL. Functional and pathway enrichment analysis was performed with KEGG and Gene Ontology (GO) databases. RESULTS: The case report highlighted a complex clinical course where the patient initially responded well to R-CHOP chemotherapy for DLBCL, achieving remission, but later relapsed with MM, treated with ASCT and lenalidomide. The systematic review revealed 14 eligible studies in which MM and DLBCL often occur in older patients, either simultaneously or sequentially, with variable treatment responses, including complete remission, partial remission, or relapse. The bioinformatics analysis identified several shared function and cancer-related pathways between two cancers including interleukin and cytokine-mediated signaling pathways, regulation of cell cycle, neurotrophin signaling pathway, FOXO signaling pathway, Epstein Barr virus infection, and viral carcinogenesis. CONCLUSION: This study provides valuable insights into the dual occurrence of MM and DLBCL, emphasizing the importance of tailored treatment approaches. The driver mutations identified highlight overlapping oncogenic pathways rather than implying a shared clonal origin, and may inform future studies exploring their biological and clinical implications. Further research into these shared molecular mechanisms could lead to more effective treatments for patients with coexisting MM and DLBCL.

Bioinformatics analysis↗

PubMed2025

Genomic profiling of aggressive pathologic features in lung adenocarcinoma.

INTRODUCTION: Pathologic features involving LVI (lympho-vascular invasion), PNI (perineural invasion), STAS (spread through air spaces), and Grade 3 pattern (from the International Association for the Study of Lung Cancer grading system) are related to having an aggressive phenotype and linked to poor prognosis. However, few studies have conducted in-depth analyses of these features simultaneously with genomic profiling. METHODS: A total of 1559 sequencing of adenocarcinoma samples were included in the common driver mutations analysis, 1306 samples were brought into genomic mapping analysis. OncoSG's East Asian ancestry dataset was implemented for Tumor-Node-Metastasis-Biomarker (TNMB) classification and prognostic assessment. RESULTS: EGFR was more significantly prevalent in LVI negativity (P = 0.021), STAS negativity (P = 0.002), and moderate grade (P < 0.001). ALK was significantly interrelated with LVI (P = 0.028), STAS (P < 0.001), and poor grade (P < 0.001); ROS1 and STAS positivity (P = 0.031), poor grade (P = 0.016) were significantly related. KRAS (P = 0.003) and BRAF-V600E (P = 0.002) were only significantly intertwined with poor grade. Apart from common driver mutations, TP53, CHEK2, KEAP1, PTEN, RB1, NF1 were significantly enriched in LVI samples (P < 0.05). TP53, PTEN, CTNNB1, HGF, NF1 were more prominent in STAS (P < 0.01). TP53, LRP1B, NF1 were significantly more prevalent in Grade 3 pattern (P < 0.001). The mixture of STK11, PTEN, and TOP2A generated by exclusive mutations may be a potential predictor of TNMB categorization towards survival. The HR of stage II compared I of TNMB was 2.28 (95 % CI 1.36-3.86, P < 0.001), while stage III compared II was 1.95 (95 % CI 1.04-3.21, P = 0.031). CONCLUSIONS: This analysis demonstrated the correlation of pathologic features with common driver mutations, key mutations and canonical oncogenic signaling pathways. The data highlighted the similarities and differences among these features horizontally, and provide new insights in TNMB classification and prognostic assessment.

Humans↗

PubMedDate not supplied

Subject recruitment for cancer control studies in an adverse environment.

Subject recruitment in an adverse environment prompted researchers to identify a novel method to gain a different perspective on the problem. Lewin's Model of Change was used in a post hoc examination of recruitment strategies from 5 cancer control studies of breast or prostate cancer. Based on this evaluation, driving and restraining forces in recruitment were identified. Lessons learned and recommendations are discussed based on this evaluation. Five categories of restrainers were identified from this evaluation and include sociocultural, institutional, individuals, budget, and study design. Conversely, only 3 categories of drivers were elucidated by the examination: sociocultural, institutional, and individuals. Lessons and recommendations ranged from addressing institutional barriers to capitalizing on public relations. Researchers entering a new environment for recruitment would benefit from using Lewin's force field analysis before writing a proposal or implementing a project. This approach better directs energy and resources and enhances the ability of the investigator to maintain a broad, less biased perspective.

Breast Neoplasms↗

PubMed2026

Systems genetics approaches model the heritable architecture of polyendocrine metabolic ovarian syndrome.

Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is the most common endocrine disorder in women and is closely associated with complex diseases such as cardiovascular disease and type 2 diabetes. However, the mechanistic links between PMOS and its comorbidities remain poorly understood. Here, we present an integrative systems genetics platform that leverages genetic diversity in both mice and humans to dissect the drivers of PMOS and its associated complications. This framework uncovered conserved genetic and environmental factors underlying PMOS, identified susceptible cell types and organs, and elucidated mechanisms linking PMOS to subsequent pathologies. For instance, we showed that increased ovarian area contributes to both PMOS susceptibility and ovarian cancer progression, while specific ovary-heart signaling circuits modulate cardiac function with aging. We further identified ovarian SF3B1-mediated alternative splicing as a key mechanistic link between PMOS and metabolic traits. Pharmacologic inhibition of SF3B1 in mice reduced circulating testosterone, insulin, and glucose levels as well as fat mass expansion. Transcriptomics analysis of ovaries from mice and experiments using human cell lines localized these effects to exon skipping events in granulosa cells. Together, this study offers a mechanistic framework for modeling the diversity of PMOS pathologies and uncovers SF3B1-mediated splicing as a link between ovary function and systemic metabolism.

Female↗

PubMed2026

Small-Molecule Degradation of the MicroRNA-21 Precursor Rescues Pathogenic Pathways in Cellular Models of Fibrosis.

MicroRNAs (miRNAs) are short RNA molecules that bind to target mRNAs, resulting in translational repression and gene silencing. Overexpression of microRNA-21 (miR-21) is associated with various human diseases, including autosomal dominant polycystic kidney disease (ADPKD) and pulmonary fibrosis. In this study, a previously described heterobifunctional molecule, TGP-21-RiboTAC, that degrades the miR-21 precursor (pre-miR-21) in triple-negative breast cancer cells was investigated in polycystic kidney cell lines and a lung fibroblast cell line. In the former, TGP-21-RiboTAC degraded pre-miR-21 and derepressed miR-21's downstream targets, programmed cell death 4 (PDCD4) and peroxisome proliferator-activated receptor alpha (PPARα), known drivers of ADPKD. The heterobifunctional molecule also inhibited cyst growth and rescued the metabolic alterations that occur in ADPKD. In the lung fibroblast cell line, MRC-5, TGP-21-RiboTAC also reduced pre- and mature miR-21 levels, rescued transforming growth factor β (TGF-β)-induced repression of SMAD family member 7 (SMAD7), and inhibited cell invasion. Collectively, these studies demonstrate the potential of targeted RNA degradation as therapeutic agents that retard the development of organ fibrosis.

MicroRNAs↗

PubMed2022

Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S).

Drugs that directly impede the function of driver oncogenes offer exceptional efficacy and a therapeutic window. The recently approved mutant selective small-molecule cysteine-reactive covalent inhibitor of the G12C mutant of K-Ras, sotorasib, provides a case in point. KRAS is the most frequently mutated proto-oncogene in human cancer, yet despite success targeting the G12C allele, targeted therapy for other hotspot mutants of KRAS has not been described. Here we report the discovery of small molecules that covalently target a G12S somatic mutation in K-Ras and suppress its oncogenic signaling. We show that these molecules are active in cells expressing K-Ras(G12S) but spare the wild-type protein. Our results provide a path to targeting a second somatic mutation in the oncogene KRAS by overcoming the weak nucleophilicity of an acquired serine residue. The chemistry we describe may serve as a basis for the selective targeting of other unactivated serines.

Humans↗

PubMed1990

The management of inoperable gastrointestinal obstruction in terminal cancer patients.

The aim of the study was to assess vomit and pain control in terminal cancer patients with inoperable gastrointestinal obstruction, using a pharmacologic symptomatic treatment which prevents recourse to nasogastric tube placement and intravenous hydration, in hospital and home care settings. Twenty-two symptomatic patients, who were judged as inoperable, were treated with a pharmacologic association of morphine hydrochloride and scopolamine butylbromide as analgesics and haloperidol as an antiemetic. The drugs were administered by continuous subcutaneous infusion via a syringe driver or intravenously only when a central venous catheter had been inserted previously. Daily recordings included assessment of pain, number of vomiting episodes, dry mouth, drowsiness, and thirst sensation. Data were examined before starting the treatment (T0), 2 days after (T2) and 2 days before death (T-2). They showed that there was a significant decrease in the pain score (p less than 0.001) on T2 and a further decrease on T-2 (p less than 0.05). Vomiting was controlled in all patients, with the exception of three patients with upper abdomen obstruction who required nasogastric tube placement. Dry mouth showed an upward trend throughout the observation period (p less than 0.05) but was successfully treated by administering liquids by mouth or ice-cubes to suck. Drowsiness too presented an upward trend from T0 to T-2 (p less than 0.001). Only one patient out of 16 who reported to be thirsty required intravenous hydration. We believe that in terminal cancer patients, vomit and pain resulting from inoperable intestinal obstruction, with the exception of obstruction of the upper abdomen, can be controlled through administration of analgesic and antiemetic drugs, in the hospital and at home, without recourse to nasogastric tube placement or intravenous hydration.

Abdominal Neoplasms↗

PubMed2026

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans↗

PubMed1995

Current lifestyle of young adults treated for cancer in childhood.

The aim of this study was to look at the current lifestyle of young adult survivors of childhood cancer between the ages of 16 and 30 years to document their achievements and expose any psychosocial problems. Sixty six young adult survivors were contacted and asked if they and their siblings (16-30 years) would take part in a lifestyle study; 48 patients and 38 sibling controls were interviewed. This took the form of a structured lifestyle questionnaire, a self esteem questionnaire (Oxford Psychologists Press), and an unstructured interview. Fifty five per cent of patients achieved five or more A-C grades at 'O' level/GCSE compared with 62% of siblings and a national average of 30%. Despite that these patients were significantly less likely to go on to higher education than their siblings. The two groups were equally employable and earning similar salaries. There were three cases of known employer prejudice. A slightly higher percentage of patients than siblings had their driving licence. Seventeen patients felt their appearance had changed and eight felt that they had a residual physical mobility problem. Both groups were socially active and equally likely to partake in competitive sports. There was no overall difference in the self esteem of the two groups. In general the survivors of childhood cancer were coping well in their young adult life and achieving the same lifestyle goals as their siblings. However, significant problems have been identified.

Adolescent↗

PubMed2003

Prevention of cervical cancer.

Cervical screening in Australia is a successful public health initiative. Since the introduction of the National Cervical Screening Program in 1991, there has been a significant fall in incidence of and mortality from cervical cancer. Laboratory quality procedures are critical to ensuring optimal outcomes. Laboratory accreditation procedures are being reviewed in line with recent government recommendations. For a sustainable program, cost-containment issues need to be considered; screening interval, management of screen-detected abnormalities, and new technologies are the critical drivers of cost.

Accreditation↗

PubMed2002

Correctable visual impairment in an older population: the blue mountains eye study.

PURPOSE: To describe temporal changes in the characteristics of older persons with visual impairment in their better eye correctable by refraction. DESIGN: Study of two cross sections of a community 6 years apart. METHODS: The Blue Mountains Eye Study examined 3654 persons aged 49 to 97 during 1992 to 1994 (cross-section 1) and 3509 persons (2335 cohort survivors plus 1174 persons who moved to the area and age group) during 1997 to 2000 (cross-section 2). Logarithm of minimal angle of resolution visual acuity was measured before and after refraction. Correctable visual impairment was defined as visual impairment < 20/40 in the better eye before refraction that improved after refraction to no impairment (>/= 20/40). Factors associated with correctable visual impairment and persistent correctable impairment were determined. RESULTS: Cross-sections 1 and 2 had similar age-gender distributions. In cross-section 1, 7.5% of participants had correctable visual impairment, 3.6% had noncorrectable visual impairment, and 88.9% had no impairment. Corresponding rates in cross-section 2 were 5.6%, 2.7%, and 91.7%. In both cross sections, similar proportions (around 68%) of those visually impaired had correctable visual impairment and similar sociodemographic measures predicted correctable visual impairment. Cross-section 1 participants who were married, owned their home, had high job prestige, gained qualifications after high school, or were current drivers were less likely to have correctable visual impairment after controlling for age and gender. Adjusted odds for correctable visual impairment increased in those living alone, using community support services, dependent on others, with myopia, wearing distance glasses, or with low perceived health and heart disease. Histories of stroke, cancer, and diabetes were similar between groups with correctable and no visual impairment. CONCLUSION: Socioeconomic parameters, myopia, wearing distance glasses, reported health problems, and poor perceived health were associated with correctable visual impairment in this older population.

Aged↗

PubMed2003

[Screening the differentially methylated DNA sequences of colorectal cancer by methylated CpG islands amplification coupled with representational difference analysis].

OBJECTIVE: To screen the differentially methylated DNA sequences between mucosa adjacent to colorectal cancer (MACC) and normal colonic mucosa. METHODS: The methylated DNA sequences were enriched by methylation CpG islands amplification (MCA), and the differentially methylated DNA sequences between MACC and normal colonic mucosa were isolated by representational difference analysis (RDA). Similarities between the separated fragments and the human genomic DNA were analyzed with BLAST program system in GenBank. With the separated fragment 1A12 as probe, dot blot was used to study its distribution between RDA products (No. 1-4 rounds), MACC (tester) and normal colonic mucosa(driver). RESULTS: Twenty-five differentially methylated DNA sequences were obtained. Preliminary studies indicated that 1A01 fragment was concerned with two different genes (LOC256866 and CECR7), it was located in the first exon of CECR7. 1A12 fragment was located in 5 flanking region of GR6 gene. By dot blot with 1A12 probe, hybridized signals were detected in MCA product of MACC and RDA products of No. 1-4 rounds, respectively. No signal was detected in MCA product of normal colonic mucosa. CONCLUSION: The differentially methylated DNA sequences can be isolated effectively between two different tissues with MCA coupled with RDA. Different methylated DNA fragments exist between MACC and normal colonic mucosa and these fragments may be concerned with colorectal cancer.

Adult↗

PubMed2026

NOTCH1 acts as a tumor suppressor that induces early differentiation in head and neck cancer.

Inactivating NOTCH1 mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function - unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that NOTCH1 is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early differentiation, an altered tumor microenvironment, and better prognosis. Clarifying whether NOTCH1 occasionally functions as an oncogenic driver in HNSCC is crucial to prognosis and personalized therapy. The results presented unify the field, reconcile conflicting data, and provide critical insights into the biological and clinical significance of NOTCH1, with broader implications in other squamous carcinomas with NOTCH1 mutations.

Receptor, Notch1↗

PubMed2002

[Adolescents alcohol related traffic accidents and mortality in 1999-2000--problem and solutions].

There are a number of factors that give traffic accidents and injuries a prominent position among public health agenda. Injuries, major public health challenge throughout the world and which account for 10% of global mortality, are often ignored as a major cause of death and may require innovative strategies to reduce their toll. Traffic accidents prevention traditionally have been as the domain of law enforcement, societal responses have primarily been a repressive or containment nature. The role of the health sector has tended to be limited to one of treatment and disability prevention, or in other words, damage control. Global Status Report on alcohol use 2001 revealed that drinking has risen steadily among young people in Japan and children between the ages of 13 and 17 have drunk to intoxication or unconsciousness. It also appears that young people in Japan are beginning to drink at earlier ages, while research has found earlier initiation of alcohol use to be associated alcohol dependence and alcohol related injury in later in life. Motor vehicle traffic accidents are a leading cause of death among children, adolescents and young adults between 16 and 20 years of age even though high school students were prohibited from having drivers licenses by internal school rules, this age group was the primary responsible party for 30% of accidents and fatal accidents in 2000. This underlies the fact that how significant role they play as a contributors to the overall traffic problem in Japan. Unlike major causes of deaths such as cancer and heart diseases and despite the critical problem in public health, there are few epidemiological studies on youth involvement in traffic accidents, morbidity and mortality in Japan.

Accidents, Traffic↗

PubMed2005

Synthesis and pharmacology of new camptothecin drugs.

Camptothecin (CPT) drugs exhibit antineoplastic activity against colorectal, breast, lung and ovarian cancers. This review briefly summarizes the pharmacology of CPT drugs, examines four strategies and methods for the synthesis of camptothecins, and finally discusses homocamptothecins and silatecans, two new classes of CPT analog.

Animals↗

PubMed2026

Lipid Metabolism-related lncRNA Model Identifies AC026412.3 as a Driver of Fatty Acid β-oxidation in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Dysregulated lipid metabolism contributes to hepatocellular carcinoma (HCC) progression, but the prognostic value and mechanistic roles of lipid metabolism-related long noncoding RNAs (LRLs) remain insufficiently characterized. This study aimed to construct and validate an LRL-based prognostic model and to investigate the biological function and metabolic mechanism of AC026412.3 in HCC. METHODS: Transcriptomic and clinical data from the The Cancer Genome Atlas Liver Hepatocellular Carcinoma cohort were analyzed to identify LRLs based on their correlation with curated lipid metabolism genes. Differential expression, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were performed to construct a prognostic signature, which was evaluated using Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) analyses. Functional enrichment analyses Gene Ontology [GO], Kyoto Encyclopedia of Genes and Genomes [KEGG] and gene set enrichment analysis [GSEA], mutation profiling, tumor mutational burden, immune infiltration estimation, and consensus clustering were applied to characterize associated features. A key LRL was identified through integrated bioinformatic screening and prioritization. Its biological role was assessed by quantitative reverse transcription polymerase chain reactionq (RT-PCR), western blotting, BODIPY staining, colony formation, Transwell assays, and xenograft models. RNA sequencing followed by pathway enrichment analysis was conducted to explore underlying mechanisms. RESULTS: A three-LRL signature (AL031985.3, NRAV, and AC026412.3) stratified HCC patients into distinct risk groups with significantly different survival outcomes and demonstrated independent prognostic value. AC026412.3 was markedly upregulated in HCC and associated with poor prognosis. Functional assays demonstrated that AC026412.3 promoted proliferation, invasion, and tumor growth while reducing lipid accumulation. Mechanistically, AC026412.3 upregulated solute carrier family 22 member 5 (SLC22A5), enhanced fatty acid β-oxidation, and increased adenosine triphosphate (ATP) production, thereby driving metabolic reprogramming. CONCLUSIONS: This study establishes a robust LRL-based prognostic model and identifies AC026412.3 as a key regulator of lipid metabolic reprogramming via the SLC22A5-fatty acid β-oxidation axis, highlighting its potential as a biomarker and therapeutic target in HCC.

HCC↗