The immunosuppressive tumor microenvironment contributes to the poor prognosis of hepatocellular carcinoma (HCC). The transcriptional profiles of senescence-associated genes (SAGs) in peripheral blood mononuclear cells (PBMCs) are enriched with pathways linked to immune dysfunction and may serve as noninvasive proxies of systemic immune status. This study aimed to identify and validate a PBMC-derived transcriptional signature enriched with SAGs as a noninvasive prognostic tool for HCC. We performed RNA sequencing on PBMCs from an orthotopic HCC mouse model treated with Qizhu anti-cancer prescription (QZACP). Senescence-associated differentially expressed genes (SAG-DEGs) were identified. Core candidates were screened by intersecting QZACP-modulated SAG-DEGs with predicted targets of blood-absorbed components through network pharmacology. The expression, prognostic value, and immune correlations of the core genes were validated using human HCC cohorts and public databases. We identified 587 SAG-DEGs enriched for immune pathways (e.g., interleukin-17 and tumor necrosis factor). Integration of transcriptomic and network pharmacology data identified five core genes. HSPA1A and ENPP2 were consistently upregulated in PBMCs and HCC tumor tissues. High ENPP2 expression was significantly associated with shorter overall survival, immunosuppressive tumor microenvironment features, and remained an independent prognostic factor in multivariate analysis. HSPA1A was consistently upregulated and correlated with immunosuppressive features. This study identified a PBMC-derived senescence-associated transcriptional signature associated with immunosuppression and poor HCC outcomes. ENPP2 emerged as a noninvasive independent prognostic biomarker, whereas HSPA1A was identified as a candidate biomarker associated with immunosuppression.
Tumor-associated macrophages (TAMs) play a pivotal role in breast cancer progression and therapeutic resistance. This study provides a comprehensive bibliometric analysis to delineate the global research trends, collaborative networks, and emerging hotspots in the field of TAMs and breast cancer over the past two decades. Publications related to TAMs and breast cancer were retrieved from the Web of Science Core Collection (2004–2026). Bibliometric analysis was conducted using VOSviewer (v1.6.20), CiteSpace (v6.4.R1), and the R package “Bibliometrix” (v4.5.3). A total of 2,253 articles were included, revealing a steady and significant increase in annual publications. While China emerged as the most productive country in terms of publication volume (909 articles), the United States led in citation impact (40,581 citations). Sun Yat-sen University was the most prolific institution. Keyword co-occurrence analysis identified four primary research clusters: immunotherapy, TAM biology, molecular mechanisms, and prognostic significance. Temporal analysis demonstrated a clear thematic evolution, with early research focusing on foundational concepts like “angiogenesis” and “growth factor”. More recently, keyword burst analysis highlighted the current research frontier, with “triple negative breast cancer” (TNBC), “cancer immunotherapy”, “delivery”, “blockade”, “macrophage polarization”, “protein” and “metabolism” showing the strongest and most sustained activity since 2021. Our analysis reveals a clear research trajectory toward TAM-targeted nanomedicine and ICD, particularly for TNBC, identifying these as the dominant frontiers for future investigation.
Gastric cancer (GC) is one of the primary contributors to cancer-associated deaths worldwide due to its aggressive progression and limited effective therapeutic strategies. Increasing evidence suggests that N6-methyladenosine (m6A) RNA methylation contributes to GC development, although its downstream targets are not fully understood. This study explores the biological role of prolyl 4-hydroxylase subunit alpha 3 (P4HA3) and regulation by m6A methylation. Bioinformatic analyses of public datasets identified prognosis-related genes in GC. P4HA3 silencing experiments in GC cell lines and mouse xenograft models evaluated its influence on proliferation, migration, invasion, and tumor growth in vivo. Interactions among P4HA3, ZC3H13, and IGF2BP1 were examined using qRT-PCR, western blotting, MeRIP, mRNA stability, RIP, and dual-luciferase reporter assays. Rescue experiments were performed to assess whether GC malignancy depended on the ZC3H13–P4HA3 regulatory axis. Bioinformatic analyses identified P4HA3 as an upregulated gene in GC associated with poor overall survival. P4HA3 silencing suppressed GC cell malignant properties, and tumor growth in vivo. Mechanistically, ZC3H13 overexpression increased P4HA3 mRNA and protein levels by promoting m6A-dependent mRNA stability. ZC3H13-mediated m6A methylation facilitated IGF2BP1 binding to P4HA3 transcripts, sustaining its expression. Rescue assays showed that ZC3H13 restoration partly reversed the effects of P4HA3 silencing via PI3K/AKT signaling pathway. In addition, GEPIA analysis revealed that ZC3H13–IGF2BP1–P4HA3 axis exhibited clinical prognostic relevance in GC. This work identifies P4HA3 as an m6A-regulated oncogene in GC and reveals a ZC3H13–IGF2BP1–P4HA3 axis that promotes tumor progression, providing a probable therapeutic target.
Pancreatic cancer (PC) is characterized by marked intratumor heterogeneity and an immunosuppressive microenvironment, resulting in poor therapeutic responses. This study aimed to identify core cell subsets and critical regulatory targets driving PC malignant progression through a multi-omics integration approach. Public datasets from TCGA, GEO, and IEU-Open-GWAS were analyzed using scRNA-seq, scPagwas, BayesPrism, and WGCNA tools to screen for core cells and genes in PC. The expression of core genes was validated by Western blot and qPCR, while PC cell functions were assessed via EdU, colony formation, and Transwell assays. Integration of scRNA-seq and scPagwas identified PI3 + Epithelial cells as a core PC subpopulation, with strong prognostic relevance—patients with high abundance of this subset exhibited shorter survival. The infiltration of PI3 + Epithelial cells correlated with PC’s immunosuppressive microenvironment and somatic mutation profiles. Among candidate core genes, the Myeloma overexpressed (MYEOV) gene was upregulated in PC. Functional experiments demonstrated that MYEOV accelerates PC progression in association with FGFR3-related MAPK signaling. This study confirms PI3 + Epithelial cells as a core cell subset driving PC progression and MYEOV as a key gene associated with this subset. MYEOV promotes PC progression partly through regulating FGFR3-associated MAPK signaling.
The p53 tumor suppressor is among the most valid oncogenes targets. Although translation of p53-based therapies has had inconsistent results regardless of strong preclinical validation, it remains evident that a clear gap exists between the biological rationale and therapeutic durability. This review is a critical assessment of p53-directed strategies, like mutant p53 reactivation, activation of suppressed wild-type p53 via MDM2/MDMX inhibition, gene replacement strategies, and targeting the loss of p53. This review is not to enlist therapeutic agents or pathways, but instead to evaluate the constraints for translation, i.e. pathway dependency, and limitations on the therapeutic window, and trial design mismatch, that have chosen clinical outcomes. Experiences of failures of late-stage clinical trials show that p53 targeting/restoration is often not sufficient to produce a lasting tumor remission. The future directions are in allele-specific mutant targeting, patient stratification based on biomarkers, adaptive trial design, and rational combination strategies that increase the level of stress beyond tolerable levels. The structurally druggable alleles are only a small minority of TP53-mutant disease, with the Y220C hotspot accounting for approximately 1.8
Homoharringtonine (HHT), a natural alkaloid approved for treating hematological malignancies, has shown potential activity against solid tumors, but its role in cervical cancer remains unexplored. This study investigates the anti-cervical cancer effects of HHT and its impact on the EGFR/PI3K/AKT/mTOR signaling pathway. The anti-proliferative, anti-migratory, cell cycle, and pro-apoptotic effects of HHT were evaluated in HeLa and SiHa cervical cancer cells using CCK-8, colony formation, wound healing, Transwell migration, and flow cytometry assays. Protein expression levels of EGFR/PI3K/AKT/mTOR pathway components and their phosphorylated forms were assessed by Western blotting, while network pharmacology, molecular docking, and RNA sequencing were employed to identify potential targets. An in vivo xenograft mouse model was used to evaluate tumor growth inhibition and systemic toxicity. HHT dose-dependently suppressed proliferation, colony formation, and migration of HeLa and SiHa cells, with calculated IC₅₀ values of 62.96 nM and 56.09 nM, respectively, while inducing S-phase arrest and apoptosis. Network pharmacology and transcriptomic analysis pointed to the EGFR/PI3K/AKT/mTOR axis as a key pathway involved, and molecular docking predicted stable binding of HHT to EGFR (-8.8 kcal/mol). Western blotting confirmed that HHT dose-dependently reduced phosphorylation of EGFR (Y1068), PI3K (Tyr458), AKT (Ser473), and mTOR (Ser2448). In the HeLa xenograft model, HHT (0.5 mg/kg/day) significantly inhibited tumor growth without causing body weight loss or major organ toxicity. Collectively, HHT exerts potent anti-cervical cancer activity, with the EGFR/PI3K/AKT/mTOR signaling pathway pointed to as a key mediator of its effects, leading to cell cycle arrest and apoptosis. These findings establish HHT as a promising therapeutic candidate for cervical cancer with a favorable safety profile.
Lymph node ratio (LNR), defined as the ratio of positive lymph nodes to the total nodes harvested, has emerged as a potential prognostic marker in oral tongue squamous cell carcinoma (OTSCC). This study aimed to evaluate the prognostic significance of LNR in patients with OTSCC and its association with overall survival (OS), disease-free survival (DFS), and pathological features. A retrospective cohort study was conducted, including 127 patients with biopsy-proven OTSCC treated between 2008 and 2023. LNR was calculated and stratified into two groups using a cutoff value of 0.01 determined by receiver operating characteristic (ROC) analysis. Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. The median LNR was 0.01 (n = 59 for LNR < 0.01; n = 68 for LNR ≥ 0.01), and ROC analysis identified 0.01 as the optimal cutoff (AUC = 0.748). Patients with LNR ≥ 0.01 demonstrated significantly worse 5-year OS (43.3
Tumor metastasis is the process by which tumor cells spread from the primary tumor to distant organs. This process is not random. Different tumor types often tend to spread to specific organs. This phenomenon is known as tumor metastatic organotropism. This study aimed to systematically analyze global research trends and insights into tumor metastatic organotropism, focusing on key mechanisms and treatment strategies to support future advances. The Web of Science Core Collection was searched for documents from its inception in 1974 to 28 September, 2025. Bibliometric analyses and visualizations were conducted using VOSviewer, CiteSpace, Bibliometrix, R, Scimago Graphica, and Pajek. The analysis mainly covered publication trends, countries, institutions, journals, authors, cited references, and keywords. These elements were used to uncover internal structures and interconnections within the field. A total of 7,206 authors from 1,566 institutions across 75 countries contributed 1088 papers on tumor metastatic organotropism published in 486 journals. Global research on tumor metastatic organotropism has shown steady and significant growth. Most publications originated from the United States, China, and Germany. Notably, the United States had the highest number of publications, citation counts, and contributing institutions. Memorial Sloan Kettering Cancer Center had the highest institutional publication output in this field. Cancer published the highest number of articles, whereas Cancer Research received the most citations (2,811). Yibin Kang had the highest publication output among the identified authors, contributing fifteen publications. Among the types of cancer metastasis, research on trends in breast, lung, and colorectal cancers is relatively prevalent. Keyword co-occurrence and citation burst analyses identified the pre-metastatic niche, exosomes, and immunotherapy as prominent topics in the analyzed study. This bibliometric study offers a comprehensive overview of the current landscape of tumor metastatic organotropism research. By summarizing the current situation in this field and identifying research trends, this study may provide useful insights and references for researchers aiming to effectively prevent and treat tumor metastatic organotropism in the future.
Cancer stem cells (CSCs) are a small but highly plastic subpopulation of tumor cells that play essential roles in tumor initiation, heterogeneity, metastasis, therapeutic resistance, and recurrence. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of CSC biology through diverse molecular mechanisms. They can modulate chromatin architecture, epigenetic modifications, transcriptional activity, RNA stability, alternative splicing, protein function, signaling pathway activation, intercellular communication, and even micropeptide production. Through these regulatory modes, lncRNAs influence key CSC properties, including self-renewal, proliferation, survival, differentiation, metabolic plasticity, epithelial–mesenchymal transition, immune evasion, and drug resistance. Increasing evidence indicates that lncRNAs regulate major stemness-associated pathways, such as Wnt/β-catenin, Notch, Hedgehog, Hippo/YAP, TGF-β, and PI3K/AKT signaling, thereby sustaining CSC phenotypes and promoting tumor progression. In addition, CSC-associated lncRNAs may serve as promising biomarkers for diagnosis, prognosis prediction, recurrence monitoring, and therapeutic response evaluation. Therapeutic strategies targeting lncRNAs, including antisense oligonucleotides, small interfering RNAs, CRISPR/Cas-based approaches, and nanoparticle-mediated delivery systems, offer potential opportunities to eliminate CSCs and overcome treatment resistance. However, the clinical translation of lncRNA-targeted therapies remains limited by tumor heterogeneity, context-dependent lncRNA functions, delivery efficiency, off-target effects, and safety concerns. In this review, we summarize the molecular mechanisms of lncRNA action, discuss the functional roles of lncRNAs in CSC regulation, and highlight their clinical implications as biomarkers and therapeutic targets. A deeper understanding of lncRNA-mediated CSC regulation may provide new insights into cancer progression and support the development of more precise strategies to prevent tumor relapse and improve therapeutic outcomes .
This study aimed to investigate the potential anti-colorectal cancer (CRC) effects and molecular mechanisms of organic acids from Lonicera japonica Thunb. Active organic acid constituents were collected through literature review and database screening, followed by pharmacokinetic evaluation. Network pharmacology was applied to predict potential targets, which were intersected with CRC differentially expressed genes from the GEPIA database. GO and KEGG enrichment analyses explored the biological functions and signaling pathways. Core targets were identified through network topology analysis and random forest algorithms, with their prognostic and diagnostic relevance evaluated using TCGA and GEO datasets. Molecular docking was used to predict possible binding modes and binding energies between compounds and candidate targets. Furthermore, the anti-cancer effects of caffeic acid methyl ester (CAME) were preliminarily evaluated in HCT116 cells through CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays. Western blot was performed to detect the expression of ERK and p-ERK. Four representative organic acid compounds and 117 potential targets were identified. Enrichment analysis suggested involvement in inflammatory responses, immune regulation, and cancer-related signaling pathways. DPP4 and MAPK1 were prioritized as candidate core targets with altered expression patterns and potential clinical relevance in CRC. Molecular docking suggested potentially favorable interactions between selected compounds and predicted core targets. Experimental results showed that CAME significantly inhibited HCT116 cell proliferation, colony formation, and migration in a dose- and time-dependent manner (IC50 = 16.06 µM at 48 h). CAME also induced cell apoptosis and significantly downregulated p-ERK protein levels. Under the tested conditions, the combination of CAME and SCH772984 further reduced cell viability and p-ERK levels compared with either single treatment; however, the nature of this interaction remains unknown. Organic acids from Lonicera japonica Thunb., particularly CAME, may exert anti-CRC effects, at least in part, in association with reduced ERK phosphorylation. Bioinformatics analyses also suggested that predicted targets may be related to immune- and tumor microenvironment-associated pathways, which require further experimental validation. This study provides preliminary computational and in vitro evidence supporting further investigation of Lonicera japonica Thunb. organic acids as candidate natural compounds for CRC-related research.
Traditional ex vivo engineered immune cell therapies, such as CAR-T and TCR-engineered T cells, have revolutionized cancer treatment but face hurdles in solid tumors. These centralized, systemically deployed approaches are biologically detached from tumor ecosystems, resulting in high manufacturing costs, systemic toxicity, and poor persistence. To overcome these limitations, an emerging paradigm shifts focus toward Tissue-Localized Immunoengineering. This strategy programs, activates, regulates, and renews immune cells directly within their native tissue microenvironments. By operating in vivo, it transforms engineered immunity from a lab-derived cellular product into a spatially precise, evolution-aware, and environment-aware biological system. This approach preserves tissue-resident identity, epigenetic fidelity, and ecological balance, offering enhanced timeliness, quantitative control, and long-term oncological resilience. This review summarizes the biological justification, mechanisms, delivery success vectors, design principles, and translational barriers that are relevant to in vivo tissue-localised immunoengineering for cancer, both from a biological and molecular standpoint. Specific focus on tumor-responsive sensing systems, synthetic genetic circuits, delivery efficiency in solid tumors, programmable safety mechanisms, and new ideas for clinical translation.
CLDN18.2-directed therapy has expanded biomarker-selected treatment options for gastric and gastroesophageal junction adenocarcinoma, whereas FGFR2b-directed therapy has shown clinical activity but remains investigational. Clinical interpretation depends on treatment-specific assays, thresholds, sampling quality, and the strength of evidence supporting each intervention. This review distinguishes evidence-supported clinical practice from exploratory biomarker strategies and author-proposed conceptual frameworks. We synthesized clinical and translational evidence across immunotherapy-era standards of care, emphasizing trial design, diagnostic variability, intratumoral heterogeneity, treatment deliverability, and implementation barriers. Evidence was organized into three levels: prospective evidence supporting current practice, emerging clinical or translational evidence, and author-proposed hypotheses requiring prospective validation. SPOTLIGHT and GLOW provide randomized phase III evidence for zolbetuximab plus chemotherapy in patients selected with a treatment-specific CLDN18.2 assay and threshold. FAST and FIGHT provide supportive phase II evidence, while FORTITUDE-101 supplies phase III evidence for FGFR2b enrichment but with attenuation of the overall-survival effect at longer follow-up; FGFR2b-directed therapy therefore remains investigational. Genomic profiling, transcriptomics, multiplex immunofluorescence, digital pathology, and artificial intelligence-assisted pathology may complement IHC, but none currently replaces a validated protein-based companion diagnostic. Re-testing, dependency-first selection, cutoff engineering beyond validated criteria, and the deliverability gate remain hypothesis-generating or selectively applicable strategies rather than established standards. Current clinical implementation should remain anchored to treatment-specific companion diagnostics, regulatory criteria, and prospective trial evidence. Complementary biomarkers and adaptive re-testing strategies are promising but require prospective validation. The dependency-first, cutoff-engineering, and deliverability frameworks are presented as research hypotheses and not as clinical recommendations.
To develop and validate a prognostic model based on palmitoylation‑related genes for risk stratification in acute myeloid leukemia (AML), and to explore its associations with the immune microenvironment, drug sensitivity, and single‑cell expression patterns. A five‑gene prognostic signature was constructed using univariate Cox regression and LASSO‑Cox analyses in the TCGA‑LAML training cohort (n = 131) and validated in an independent GEO cohort (GSE71014, n = 104). Risk scores were calculated, and patients were divided into high‑ and low‑risk groups. Overall survival (OS) was compared by Kaplan‑Meier curves, and model performance was evaluated by time‑dependent ROC. Immune cell infiltration, immune checkpoint expression, and drug sensitivity (predicted IC50) were analyzed. Single‑cell RNA‑seq data (GSE116256) were used to examine cell‑type specific expression of the model genes. The five‑gene model (LYPLA2, ZDHHC11, ZDHHC7, ABHD6, ABHD17C) significantly distinguished high‑risk patients with poorer OS in both training (P < 0.001) and validation (P < 0.001) sets, with AUCs of 0.72, 0.73, 0.75 (training) and 0.67, 0.70, 0.60 (validation) for 1‑, 3‑, and 5‑year survival. Multivariate Cox regression confirmed independent prognostic value (HR = 2.78, P < 0.001). High‑risk patients showed increased regulatory T cells, activated dendritic cells, and follicular helper T cells, along with positive correlations with PD‑1, TIM‑3, LAG3, and VISTA expression. Ninety‑eight compounds with differential predicted IC50 values were identified. Single‑cell analysis revealed LYPLA2 and ZDHHC7 enrichment in monocytes/macrophages and dendritic cells. The five‑gene palmitoylation‑associated prognostic model effectively stratifies AML patients by risk, reflects immune microenvironment dysregulation, and offers potential guidance for personalized therapy.
Colorectal cancer (CRC) remains a major cancer burden, and non-invasive molecular candidates remain relevant to screening-adjacent research. We asked whether public blood transcriptomes nominate UPP1 as a myeloid/monocyte-associated CRC blood-signal candidate. Candidate generation was exploratory: a staged screen of the same three blood-related datasets retained NACA, UPP1, and GLOD4, after which a pre-lock GSE203024 shortfall check led to UPP1 being fixed as primary before the controlled full analysis. UPP1 was CRC-high in GSE164191 whole blood, GSE47756 peripheral blood monocytes, and GSE203024 peripheral blood, with apparent descriptive AUCs of 0.706, 0.872, and 0.649, respectively. GSE203024 compared CRC with no-known-cancer controls, not healthy-only controls. Whole-transcriptome Benjamini-Hochberg FDR remained significant in all three datasets. The expression association remained after age/sex adjustment and in analyses restricted to participants aged at least 50 years; however, clinical metadata were incomplete and residual confounding remains possible. Marker-correlation audits indicated low heuristic composition-confounding risk but could not replace measured blood counts, flow cytometry, or formal deconvolution. GSE132465 and the independent GSE146771 study placed UPP1 mainly in myeloid-related compartments; neither supplied a healthy-versus-CRC blood single-cell comparison. The preserved in silico virtual-knockout and observational UPP1-high myeloid-state modules supported inflammatory and uridine/pyrimidine hypotheses without establishing causality. Because candidate selection and AUC estimation used overlapping retrospective datasets, the AUCs are subject to selection optimism and are not independent validation. No clinical threshold, sensitivity/specificity pair, diagnostic algorithm, or decision-curve analysis was derived. UPP1 is therefore a public-data candidate, not a validated diagnostic, prognostic, or mechanistic biomarker.
To investigate long non-coding RNA (lncRNA) MIR210HG expression in high-grade serous ovarian cancer (HGSOC) and its correlation with clinicopathological features, clinical outcomes, and prognosis. Tissue samples were collected from 84 patients with HGSOC undergoing surgical treatment at the Affiliated Hospital of Qingdao University from 2019 to 2021. Fifty-seven patients undergoing total hysterectomy and bilateral adnexectomy resection for uterine fibroids and adenomyosis during the same period were also included. MIR210HG expression was detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Univariate and multivariate logistic regression analyses were used to assess correlation with advanced FIGO stage and clinical outcomes. The Kaplan-Meier plotter was used to predict the correlation between MIR210HG expression and prognosis, considering pathological classification, clinical stage, and TP53 status. MIR210HG expression was significantly upregulated in HGSOC compared to normal ovarian and fallopian tube tissues. MIR210HG expression was moderately and weakly correlated with CA125 (r = 0.515, P < 0.001) and HE4 levels (r = 0.325, P = 0.001), respectively. Advanced clinical stage was associated with higher MIR210HG expression. Patients with lymph node metastasis and ascites also exhibited higher MIR210HG expression (P < 0.05). MIR210HG was associated with FIGO stage, while CA125 ≤ 35 U/ml and FIGO stage II were independent protective factors for composite poor clinical outcomes. Patients with low MIR210HG expression had a significantly longer 5-year progression-free survival (PFS) compared to those with high expression. What’s more, MIR210HG expression was significantly correlated with both 5-year PFS and overall survival (OS) in TP53-mutant patients, as opposed to only OS in TP53 wild-type patients. MIR210HG expression is significantly upregulated in HGSOC and is associated with clinical stage, lymph node metastasis, and ascites. MIR210HG expression exhibited survival associations based on TP53 status, suggesting biomarker potential for HGSOC.
Cervical small cell neuroendocrine carcinoma (SCNEC) admixed with squamous cell carcinoma (SCC) is a rare malignancy associated with a poor prognosis. While histological features of this mixed tumor have been described, liquid-based cytology (LBC) findings remain largely undocumented, despite prior multi-center studies describing pure SCNEC. Herein, we report a case of mixed cervical SCNEC-SCC in a 69-year-old woman. The lesion was initially suspected via LBC screening and subsequently confirmed using limited cervical biopsy specimens, no surgical resection specimen was available. Cytologically, the SCNEC component presented as small round cells in loose clusters or isolated single cells, exhibiting a high nuclear-to-cytoplasmic ratio. These cells typically featured delicate yet irregular nuclear membranes, hyperchromatic nuclei, inconspicuous nucleoli, scant cytoplasm, frequent crush artifacts, scattered mitoses, and focal tumor necrosis. In contrast, other cells displayed slightly more abundant cytoplasm with visible nucleoli, representing the SCC component. We quantitatively describe component proportions using a multi‑pathologist consensus‑based cell‑counting approach and elaborate on characteristic cytologic features, including tumor necrosis, mitotic activity, and crush artifacts, to facilitate differential diagnosis. Owing to sampling limitations intrinsic to small size biopsy specimens, histologically derived tumor component percentages should be interpreted prudently, as they may not reflect the true composition of the entire lesion. Careful evaluation of atypical malignant cells on LBC is essential to avoid misdiagnosis of this aggressive neoplasm. Importantly, although LBC can identify dual-lineage malignant cells during screening, this single case study cannot establish causal or correlative links between cytological detection and overall survival. Early cytological recognition failed to improve clinical outcomes in this patient, who presented with widespread radiologically suspected metastatic disease at initial diagnosis; therefore, no generalized survival conclusions can be drawn from this single case.
This research was designed to investigate the functional impact of miR-217 on proliferative activity and apoptotic processes in pancreatic carcinoma cells, and to explore its associated molecular mechanisms. Five matched pairs of pancreatic ductal adenocarcinoma specimens and corresponding adjacent non-neoplastic tissues were obtained. Quantitative real-time PCR (qRT-PCR) was utilized to assess the expression levels of miR-217. In the PANC-1 cellular model, gain-of-function and loss-of-function strategies were implemented through transfection with an miR-217 mimic or an antisense oligonucleotide (ASO), respectively. Plasmid-based overexpression and short hairpin RNA (shRNA)-mediated knockdown were utilized to modulate ENO1 expression. Cell proliferation was assessed using the MTT and colony formation assays. Apoptotic rates were quantified using flow cytometric analysis. Western immunoblotting was performed to determine protein expression of ENO1, AKT1, N-cadherin, E-cadherin, and Vimentin. The direct binding of miR-217 to the 3′-untranslated region (3′-UTR) of ENO1 mRNA was confirmed using a dual-luciferase reporter system. Functional rescue studies were conducted to evaluate the regulatory relationship between miR-217 and ENO1. miR-217 expression was markedly downregulated in pancreatic tumor tissues. Ectopic overexpression of miR-217 suppressed PANC-1 cell proliferation and induced apoptosis. At the mechanistic level, miR-217 upregulation led to reduced expression of ENO1, AKT1, N-cadherin, and Vimentin, accompanied by elevated E-cadherin levels. The dual-luciferase assay confirmed direct binding of miR-217 to the 3′-UTR of ENO1. Restoration of ENO1 expression counteracted the suppressive influence of miR-217 on proliferation and its promotive effect on apoptosis. miR-217 is underexpressed in pancreatic cancer and functions as a tumor suppressor by directly targeting ENO1. This regulation is associated with altered expression of AKT1 and epithelial–mesenchymal transition (EMT) markers, which may contribute to the inhibition of proliferation and promotion of apoptosis in pancreatic cancer cells.
Gastric cancer (GC) ranks fifth in global incidence and third in cancer-related mortality. Omics technologies have become essential for decoding intratumoral heterogeneity and the spatial architecture of tumors, leading to a surge in omics-based research on gastric cancer. This study systematically maps the landscape, evolving trends, and emerging frontiers of omics applications in gastric cancer through a comprehensive bibliometric analysis. Publications were retrieved from the Web of Science Core Collection and Scopus databases, covering the period from the inception of these databases to December 31, 2025. A total of 1,382 documents were analyzed using CiteSpace, VOSviewer, and the Bibliometrix R package, focusing on six dimensions: country/region, institution, author, source journal, reference, and keyword. The annual publication output has consistently increased, with China, the United States, and Japan at the forefront of productivity. High-frequency keywords such as gastric cancer, radiomics, biomarker, and proteomics delineate the core thematic structure of the research. Co-occurrence clustering analysis revealed six distinct clusters, prominently featuring radiomics, epigenetics, and gastric cancer. Additionally, keyword burst detection analysis identified machine learning and radiomics as current research frontiers, while citation analysis underscored therapeutic strategies as a central hotspot in the field. The number of publications in the field of GC omics research has shown a sustained increase, reflecting the growing interest in omics technologies. With the advancement of omics technologies, research efforts have gradually expanded from single-omics analysis to encompass epigenetics, radiomics, and multi-omics integration, with genomics and proteomics consistently playing central roles. In this context, the development of novel biomarkers through omics analysis provides key evidence for elucidating the mechanisms underlying GC initiation and progression, predicting disease risk, and optimizing therapeutic strategies. Current research priorities include biomarker screening and exploration of pathogenic mechanisms based on omics technologies to enable early GC screening, facilitate drug development, and enable efficacy evaluation. The integration of multi-omics data with deep learning to construct early risk prediction models for GC, with subsequent application to targeted therapy and immunotherapy, represents a promising research direction.
Chronological age may influence immune function, but individuals of the same age may differ in biological aging. We evaluated the association between biological age and clinical outcomes in patients with solid tumors treated with immune checkpoint inhibitor monotherapy. This retrospective two-center study included 302 patients with advanced solid tumors receiving ICI monotherapy. Biological age was estimated using the Levine PhenoAge model. Age-adjusted biological aging (PhenoAgeAccel) was defined as the residual from regression of PhenoAge on chronological age. Survival outcomes were compared according to PhenoAgeAccel status. The median age was 67 years; most patients had non–small cell lung cancer (78.5
Pancreatic cancer (PC) has a poor prognosis, and treatment is largely ineffective because of its unique tumor microenvironment (TME). We identified key cell types in PC using the GSE197177 dataset generated through single-cell RNA sequencing (scRNA-seq) analysis. Using TCGA-PAAD data, prognosis-related cell subtypes were identified by BayesPrism and Cox regression. Hub cell subtype-related prognostic genes were screened by integrating high-dimensional weighted gene co-expression network analysis (hdWGCNA), differential expression analysis, univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression. The upstream regulatory factors of prognostic genes were predicted. A risk model and nomogram were generated and validated, with risk scores used to evaluate pathways, the TME, immunotherapy, and drug sensitivity. Fibroblasts were identified as the key cell type in PC. TPM1+ myofibroblastic cancer-associated fibroblasts (CAFs) (myCAFs) were considered the prognosis-related hub cell subtype. AHNAK2, ARHGAP32, EVL, PRKCI, PTGES, and S100A16 were identified as prognostic genes. Regulatory factors, including DPF2 and hsa-miR-107, were predicted to target the prognostic genes. The constructed risk model and nomogram showed promise in prognostic performance, although further validation in diverse clinical subgroups is needed. Risk scores were associated with pathways, including the cell cycle, infiltration of immune cell types such as T follicular helper cells, response to immune checkpoint blockade therapy, and sensitivity to drugs such as lapatinib. A risk model based on six TPM1+ myCAF-related prognostic genes was constructed, which exhibited robust predictive ability. Our results provide novel insights into TPM1+ myCAF-related mechanisms and PC prognostic prediction, although the model’s generalizability to all patient subgroups requires further examination.
