Mixed invasive mucinous adenocarcinoma and non-mucinous adenocarcinoma (mixed IMA/NMA) is a rare subtype of lung adenocarcinoma (LUAD) with limited available data. This study aimed to comprehensively analyze the characteristics of this rare entity. A total of 738 surgical cases were enrolled, including 349 pure invasive mucinous adenocarcinoma (IMA), 61 mixed IMA/NMA and 328 pure non-mucinous adenocarcinoma (NMA) cases. Using amplification refractory mutation system, immunohistochemistry, and DNA-/RNA-based next-generation sequencing (DNA and RNA NGS), distinct molecular features were identified in mixed IMA/NMA cases compared with IMA and NMA cases, particularly in EGFR, KRAS, and ALK alterations and PD-L1 expression status. Paired analysis of the IMA and NMA components within mixed IMA/NMA cases using DNA and RNA NGS revealed one to three shared genomic alterations between the two components in the same tumor. However, significant differences were observed in the levels of cancer-associated fibroblasts, protumor cytokines, MHC-II, coactivation molecules, T cells, and effector cells between the components. Similarly, multiplex immunofluorescence assay demonstrated that immune cell infiltration, including CD4+ and CD8+ T cells, was significantly higher in the NMA components compared to the IMA components. Postoperative follow-up revealed no significant difference in disease-free survival (DFS) or overall survival (OS) between NMA and mixed IMA/NMA cases; however, both groups showed significantly shorter DFS (P = 0.011) and OS (P = 0.027) compared to IMA cases. Together, this study provides a comprehensive characterization of the molecular profiles, clonal relatedness, tumor heterogeneity, and surgical outcomes of mixed IMA/NMA, which may inform diagnostic and therapeutic strategies for this rare LUAD subtype.

Objective: To systematically investigate the pan-cancer expression, prognostic significance, immune relevance, and functional role of OAS1 in cervical cancer. Methods: OAS1 expression, genetic alterations, prognosis, cancer stemness, RNA modification, immune infiltration, and immunotherapy-related indicators were analyzed using TCGA, GTEx, HPA, GEPIA3, SangerBox, cBioPortal, TIMER3.0, and CAMOIP databases. GO and KEGG enrichment analyses were performed for OAS1 co-expressed genes. In cervical cancer, OAS1 expression was validated by immunohistochemistry and Western blotting. Stable OAS1 knockdown and overexpression HeLa cell lines were established to evaluate migration, invasion-related phenotypes, and reactive oxygen species levels. Single-cell analyses were used to characterize the cell-type-specific expression and distribution of OAS1. Results: OAS1 was upregulated at both mRNA and protein levels in multiple cancers, particularly cervical cancer. Its expression was associated with tumor stage, metastasis, genetic alterations, prognosis, cancer stemness, RNA modification-related genes, immune infiltration, TMB, MSI, and immune checkpoint molecules in a cancer type-dependent manner. OAS1 co-expressed genes were mainly enriched in type I interferon signaling, antiviral response, and innate immune pathways. In cervical cancer, OAS1 was highly expressed in tumor tissues. OAS1 overexpression promoted HeLa cell migration and increased ROS levels, whereas OAS1 knockdown suppressed migration/invasion-related phenotypes and reduced ROS levels. Single-cell showed that OAS1 was mainly expressed in epithelial/tumor cells and monocyte/macrophage populations. Conclusion: OAS1 may serve as a diagnostic, prognostic, and immune-related biomarker across cancers. In cervical cancer, OAS1 may promote malignant phenotypes by enhancing migration, invasion-related behavior, and oxidative stress, suggesting its potential as a therapeutic target.

Gastric cancer (GC) is one of the most common malignant tumors worldwide. Emerging evidence has shown that abnormal microRNAs (miRNAs) expression is involved in tumorigenesis. MiR-329 was previously reported to act as a tumor suppressor or oncogene in some types of cancer. However, its function in gastric cancer (GC) is unclear. Here, we found that miR-329 was down-regulated in GC compared with adjacent controls. Enforced expression of miR-329 inhibited proliferation, migration and invasion of gastric cancer cells in vitro. We identified T lymphoma invasion and metastasis 1 (TIAM1) gene as potential target of miR-329. MiR-329 levels inversely correlated with TIAM1 expression in GC. Importantly, TIAM1 rescued the miR-329-mediated inhibition of cell invasion and proliferation. Finally, reintroduction of miR-329 significantly inhibited tumor formation of GC in the xenograft mice. Our findings suggest that miR-329 is a tumor suppressor and potential therapeutic target of GC

BACKGROUND:Myocardial ischemia/reperfusion injury triggers profound metabolic reprogramming and lactate accumulation. However, how this metabolic stress regulates inflammatory gene expression remains poorly understood. We hypothesized that lactylation, a lactate-derived posttranslational modification, links metabolic stress to aberrant RNA splicing and cardiac inflammation through the RNA-binding protein HNRNPK (heterogeneous nuclear ribonucleoprotein K). METHODS:We analyzed atrial tissues from patients undergoing cardiopulmonary bypass and murine ischemia/reperfusion hearts to assess lactylation dynamics. Lactylation-specific proteomics, RNA sequencing, and crosslinking and immunoprecipitation followed by quantitative polymerase chain reaction were used to identify HNRNPK targets. Mechanisms were defined using site-directed mutagenesis (HNRNPK-K405R), isoform-specific overexpression, and a therapeutic splice-switching antisense oligonucleotide in mice and cardiomyocytes. RESULTS:Reperfusion significantly increased global protein lactylation in human and murine myocardium. Proteomics identified HNRNPK as a key target, specifically lactylated at lysine 405 (K405la). Ischemia-induced K405la promoted HNRNPK binding to Jag2 pre-mRNA, suppressing exon 10 skipping and shifting splicing from the Jag2 (Jagged2) short (Jag2-S) to the long (Jag2-L) isoform. Jag2-L, but not Jag2-S, exhibited high affinity for Notch1, hyperactivating Notch-NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling and exacerbating inflammation and infarct size. Mice expressing a lactylation-deficient variant (HNRNPK-K405R) were protected from ischemia/reperfusion injury. Treatment with a specific antisense oligonucleotide (Jag2-i9) that blocks the HNRNPK-Jag2 interaction prevented Jag2-L production and attenuated cardiac dysfunction. CONCLUSIONS:HNRNPK lactylation acts as a metabolic sensor coupling lactate accumulation to pathogenic Jag2 splicing. Targeting this metabolic-splicing axis offers a precise therapeutic strategy to limit inflammation and preserve cardiac function in ischemic heart disease. REGISTRATION:URL: http://www.chictr.org.cn; Unique identifier: ChiCTR2400091959.

Immunosenescence, characterized by telomere shortening, senescence-associated T-cell subsets, and chronic inflammation, is a hallmark of biological aging. Whether these aging-related immune biomarkers can be modulated through short-term intervention and whether responses differ according to individual characteristics remain unclear. This study evaluated the effects of short-term hyperbaric oxygen therapy (HBOT) on senescence-related biomarkers and explored factors associated with individual responsiveness. In a prospective cohort study, participants underwent 30 HBOT sessions (2.5 ATA, 100

Osteosarcoma exhibits substantial metabolic heterogeneity, yet existing classification schemes typically rely on narrow pathway windows and lack cellular-source attribution. Here, we integrated bulk transcriptomes from 157 osteosarcoma tumors (PKUPH-OS, n = 70; TARGET-OS, n = 87), quantified pathway-level activity via single-sample gene set enrichment analysis (ssGSEA) across curated metabolic gene sets, and performed consensus clustering to identify three stable metabolic subtypes: Cholesterogenic (C1), characterized by mTORC1-associated lipid biosynthesis and invasion-related signaling; Redox-Catabolic (C2), dominated by detoxification, glutathione/ROS buffering, and enhanced catabolic programs alongside immune engagement; and OXPHOS-Active (C3), featuring coupled mitochondrial oxidative phosphorylation and proliferative programs. Clinically, C2 displayed favorable survival (3-year overall survival: 90.8%), whereas C1 (60.0%) and C3 (61.9%) followed adverse trajectories (overall survival, P = 0.0037; progression-free survival, P = 0.011). Single-cell RNA sequencing of 16,276 cells with inferCNV-supported malignant-cell anchoring revealed distinct cellular origins: C1 signatures mapped predominantly to stromal/mesenchymal populations, C2 signatures to immune cells, and C3 signatures to malignant tumor cells. These observations apply within osteosarcoma the well-recognized principle that bulk transcriptomic signatures reflect cellular composition, providing an explicit cell-of-origin map of metabolic subtypes that supports niche-resolved risk stratification and cell-aware therapeutic hypothesis generation.

Basal-type muscle-invasive bladder cancer (BMIBC) is characterized by aggressive metastasis and poor prognosis but lacks molecularly defined therapeutic targets. Through integrative analyses of clinical cohorts and BBN-induced mouse models, we identified KRT14 as a core oncogenic driver that orchestrates the KRT14-IGF2BP1 signaling axis to promote BMIBC progression and lung metastasis. Mechanistically, residues K294 and E295 within the KH2 domain of IGF2BP1 specifically recognize conserved residues D226 and E227 within the nuclear export signal of KRT14. This direct interaction facilitates IGF2BP1-mediated cytoplasmic trafficking and auto-stabilization of its own mRNA, establishing a positive feedback loop that amplifies IGF2BP1-targeted pro-invasive gene expression. Functional disruption of this axis suppressed primary tumor progression and lung metastasis in BMIBC models. Collectively, our findings define the KRT14-IGF2BP1 axis as a previously unrecognized, potentially targetable vulnerability in BMIBC, whose inhibition may limit aggressive disease progression and inform future therapeutic strategies.

Sepsis remains a major challenge in global clinical practice due to its persistently high mortality rate. Traditional antibiotics address symptoms rather than root causes, while the problem of drug resistance continues to escalate. Detoxification strategies such as monoclonal antibodies have shown limited efficacy in complex clinical settings, as their single-target specificity and narrow activity spectrum restrict their ability to neutralize diverse bacterial toxins. The therapeutic bottleneck lies in the absence of effective methods capable of simultaneously neutralizing Gram-negative bacterial endotoxins (such as LPS) and Gram-positive bacterial exotoxins (such as Hlα). To overcome this limitation, we drew inspiration from the natural "bait" mechanisms of living organisms to develop a biomimetic nanoscale detoxifier with broad-spectrum toxin adsorption and neutralization capacity. Specifically, chloroquine was used to inhibit autophagy lysosome formation in macrophages, promoting the release of exosomes enriched with toxin receptors CD14 and ADAM10. These exosomes (Exo) were then fused with artificial liposomes (Lip) possessing extensive membrane space to construct exosome membrane hybrid liposomes (Elip). Our results demonstrated that Elip effectively neutralized the hemolytic activity of Hlα and adsorbed LPS in vitro. In a subcutaneous HIα-induced local inflammation model, Elip completely prevented local skin and muscle tissue necrosis. In a systemic inflammation model induced by intravenous HIα, Elip significantly alleviated acute inflammatory damage in the lungs and liver, reducing key pro-inflammatory factor levels to near-normal ranges. In an LPS-induced shock model, all mice in the Elip treatment group survived. This study robustly confirmed that Elip successfully resolves the clinical challenge of simultaneously clearing endotoxins and exotoxins through a "synergistic detoxification" mechanism, offering a novel therapeutic strategy with significant translational potential that transcends traditional antibiotics for conquering sepsis.

Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors. However, the detailed mechanisms by which tumor cells evade premature senescence to malignant progression remain largely elusive. Here we reported that RBM4 adversely impacted cellular senescence to favor glutamine-dependent survival of esophageal squamous cell carcinoma (ESCC) cells by dictating the activity of LKB1, a critical governor of cancer metabolism. The level of RBM4 was specifically elevated in ESCC compared to normal tissues, and RBM4 overexpression promoted the malignant phenotype. RBM4 contributed to overcome H-RAS- or doxorubicin-induced senescence, while its depletion caused P27-dependent senescence and proliferation arrest by activating LKB1-AMPK-mTOR cascade. Mechanistically, RBM4 competitively bound LKB1 to disrupt the LKB1/STRAD/MO25 heterotrimeric complex, subsequently recruiting the E3 ligase TRIM26 to LKB1, promoting LKB1 ubiquitination and degradation in nucleus. Therefore, such molecular process leads to bypassing senescence and sustaining cell proliferation through the activation of glutamine metabolism. Clinically, the ESCC patients with high RBM4 and low LKB1 have significantly worse overall survival than those with low RBM4 and high LKB1. The RBM4 high/LKB1 low expression confers increased sensitivity of ESCC cells to glutaminase inhibitor CB-839, providing a novel insight into mechanisms underlying the glutamine-dependency to improve the efficacy of glutamine inhibitors in ESCC therapeutics.

Primary renal small cell carcinoma (PRSCC) is a rare, poorly differentiated neuroendocrine carcinoma, and its clinicopathological features and the gene mutation spectrum associated with its pathogenesis remain to be elucidated. The present study aimed to characterize the genetic mutation spectrum associated with the pathogenesis of PRSCC, identify novel driver and predisposing genes for the disease, reveal its histopathological features associated with genetic mutations and systematically summarize the clinicopathologic characteristics and prognostic factors of PRSCC patients to provide a theoretical basis for molecularly targeted therapy and prognostic assessment of PRSCC. Whole-exome sequencing (WES) was performed on PRSCC samples to characterize the spectrum of genetic mutations and the results were validated using Sanger sequencing. Immunohistochemistry (IHC) was performed to reveal the histopathological features associated with these mutations. Furthermore, based on the published literature, a population-based study was conducted by searching PubMed and EMBASE databases to systematically summarize the clinicopathologic characteristics and prognostic factors of patients with PRSCC. WES identified 113 somatic single-nucleotide variants, 26 somatic insertions and deletions and mutations in 8 predisposing genes (DST, OR10H3, PTK2B, APOBR, ZNF606, CCN4, ADCK1, and MYH2) and 10 driver genes (KRTAP10-9, HYDIN, ZNF665, KRTAP10-2, GPAM, MUC12, KRT9, CCDC168, DUSP27 and MDC1). Sanger sequencing of germline DNA identified a germline A/G variant in the HYDIN sequence, first reported in PRSCC. Furthermore, IHC analysis indicated that PRSCC was positive for CD56, Syn, insulinoma associated protein 1, CgA and neuron specific enolase. In the population-based study, the majority of patients with PRSCC were elderly (57.92±15.75 years), with a pathological tumor (T) 3/4 stage (68.3%) and presented with lymph node involvement (51.7%) and distant metastasis (51.7%). T stage was an independent prognostic factor for overall survival in patients with PRSCC (P=0.004). Driver mutations in the HYDIN gene may be a key factor in the pathogenesis of PRSCC. HYDIN may serve as a prognostic marker and a target for immunotherapy in the management of PRSCC. However, due to the extreme rarity of PRSCC, the WES analysis in the present study was based solely on individual cases. To ensure the reliability and generalizability of genetic alterations detected by WES, additional PRSCC samples, along with cell and animal experiments, are warranted to confirm the role of these genetic variants (particularly HYDIN) in PRSCC pathogenesis. The functional role of HYDIN mutations in PRSCC pathogenesis requires further validation in future research.

The low oxygen tension frequently found in tumors drives the expression of hypoxia-inducible factors (HIFs), thereby supporting rapid cancer cell proliferation and metastasis. Therefore, the prolonged expression of HIF-1α, the master regulator of the adaptation to hypoxia, is a crucial protective mechanism for solid tumor progression. Here we report that RNF122, the novel E3 ligase of HIF-1α, is a hypoxia responsive gene. Importantly, loss of RNF122 dramatically promoted breast cancer cell migration, invasion, and metastasis. In the presence of hypoxia, HIF-1α transcriptionally activates the expression of RNF122, which in turn directly interacts with HIF-1α in the cytoplasm, promoting its degradation through K27-linked polyubiquitination. Consequently, RNF122 suppresses the transcriptional activity of HIF-1α and its target gene expression, thereby inhibiting the glucose metabolism and angiogenesis of breast cancer cells under hypoxic condition. Clinically, copy number loss of RNF122 occurs in 39% of breast cancer patients, and the level of RNF122 is positively correlated with increased overall survival. Taken together, our findings discovered a negative feedback loop between RNF122 and HIF-1α that inhibits hypoxia-mediated tumorigenic activity, revealing a novel mechanism by which neoplastic cells sustain HIF-1α-dependent malignancy under hypoxic condition in RNF122-negative breast cancers.

Aging is an inevitable physiological process that occurs in living organisms and has significant implications for health and disease. As the human lifespan extends, the functionality of organs gradually diminishes, leading to the emergence of various aging-related symptoms. While it is not feasible to completely halt the aging process, investigating key molecules involved in aging can help devise valid strategies to delay its progression. Circular RNAs (circRNAs) are a novel category of non-protein-coding RNAs and are abundant in cells. Their distinctive circular structure and diverse biological functions have garnered considerable attention from the scientific community. CircRNAs play a crucial role in regulating biological processes such as the cell cycle, apoptosis, and autophagy. They are implicated in various mechanisms, including cell signaling, influencing post-transcriptional regulation, and functioning as sponges for microRNAs (miRNAs), to modulate gene expression and impact cellular senescence. This research paper sets out to elucidate the mechanisms by which circRNAs regulate gene expression, epigenetic modifications, and cellular functions, as well as to assess their potential applications in aging-associated disorders.

Cervical cancer is a prevalent malignancy among women worldwide. Long-chain non-coding rna (lncRNAs) play a key role in the development of several cancers. Here, we found that the expression of lncRNA NEAT1 was significantly increased in cervical cancer cells and tissues and was closely associated with poor patient prognosis. Subsequently, we found that down-regulation of NEAT1 inhibited the proliferation, migration and invasion of cervical cancer cells. Subsequent studies showed that NEAT1, a competitive endogenous RNA, effectively enhanced RAC1 expression by adsorbing miR-101-3p. Glycolysis-related genes were predicted to be enriched in cervical cancers with high NEAT1 expression by bioinformatics analysis and confirmed by in vivo experiments. Our results suggest that NEAT1 enhances the Warburg effect through the miR-101-3p/RAC1 axis and promotes the proliferation, migration and invasion of cervical cancer cells. Therefore, elucidating this potential mechanism and targeting the NEAT1/miR-101-3p/RAC1 pathway may provide valuable insights.

Rationale: Lung cancer remains a major global health burden with limited therapeutic options. Alternative splicing, a critical post-transcriptional process, contributes to lung cancer progression through autophagy, although the underlying mechanisms remain largely unexplored. This study aims to elucidate the role of DDX24 as a splicing factor that contributes to lung cancer progression via autophagy. Methods: To establish the link between DDX24 and lung cancer progression, we performed colony formation assays, growth curve analyses, and xenograft tumor models in nude mice. Mass spectrometry and RNA sequencing were employed to investigate the involvement of DDX24 in alternative splicing, with a specific focus on the splicing of IKBKG. The mechanisms by which DDX24 regulates autophagy were further explored using co-immunoprecipitation and luciferase reporter assays. Results: The splicing factor DDX24 is significantly elevated in lung cancer tissues. Loss of DDX24 suppresses lung cancer growth by promoting autophagy. We identified DDX24 as a splicing factor that plays critical roles in the regulation of alternative splicing. Mechanistically, DDX24 regulates the alternative splicing of autophagy-related genes, including IKBKG. We demonstrate that DDX24 directly binds to IKBKG pre-mRNA, whereas DDX24 ablation stimulates the generation of the long splicing isoform of IKBKG, thereby promoting autophagy through activating of the NF-kB signaling pathway and the transcription of the BECN1 gene. Functional rescue experiments confirm that the long IKBKG isoform-mediated autophagy confers the anti-tumor effects of DDX24 depletion. In addition, IKBKG-L is positively associated with improved survival in lung cancer patients. Conclusions: This study uncovers a novel regulatory axis involving DDX24, IKBKG splicing, and autophagy in lung cancer. Our findings suggest that targeting DDX24 may represent a promising therapeutic strategy for lung cancer treatment, offering new insights into the molecular underpinnings of this disease.

The traditional treatment for cervical cancer involves aggressive surgery combined with radiotherapy and chemotherapy. Nevertheless, these treatments have certain limitations and side effects, thus breakthroughs and advances are required in cervical cancer therapy. Magnesium alloy is a promising antitumor biomaterial with excellent biocompatibility and biodegradability. However, the potential effects of magnesium alloy on cervical tumors have not been extensively explored. Recent studies have demonstrated that adding a small amount of calcium to the magnesium matrix can reduce grain size and corrosion rate while providing good biocompatibility. We conductedin vivoandin vitroexperiments to test the antitumor properties of Mg-1%Ca alloys. The results indicated that the Mg-1%Ca alloy released Mg2+and OH-more slowly, inhibited the proliferation of SiHa and HeLa cells, induced apoptosis in tumor cells, disrupted the cytoskeleton, and inhibited cell migration and invasion. At the molecular level, Mg-1%Ca alloy significantly activated the mitochondrial apoptosis pathway and inhibited the MAPK/ERK signaling pathway. In the future, Mg-1%Ca may be employed in the treatment of cervical cancer as a novel adjuvant therapeutic material with anticancer function to prevent the occurrence and progression of cancer proliferation and metastasis.

The membrane-less nuclear stress bodies (nSBs), with satellite III (SatIII) RNAs as the hallmark, are present in primates upon sensing stresses. We report that SatⅢ DNAs, SatⅢ RNAs, and 30 nSB proteins assemble into well-organized structures shortly after stresses. The activated SatⅢ heterochromatin loci rapidly expand, resulting in reduced spatial distance and enhanced expression of adjacent genes, including the transcription suppressor NFIL3, which is known to dampen proinflammatory cytokine production. Rearranging NFIL3 loci within the nSB territory enhances NFIL3 chromatin accessibility and makes NFIL3 promoters more accessible to transcription factors heat shock transcription factor 1 (HSF1) and bromodomain containing 4 (BRD4), which are also recruited to nSBs upon stresses. Human peripheral blood mononuclear cell (PBMC)-derived macrophages under heat shock plus pathogen-associated molecular pattern treatments exhibit increased SatⅢ and NFIL3 expression, the latter of which suppresses key inflammatory cytokines. Importantly, NFIL3 expression positively correlates with SatⅢ activation in septic patients, a process positively correlated to patient survival, highlighting a role of nSBs in restraining inflammatory responses.

OBJECTIVE:Cervical cancer is the leading malignancy in terms of both incidence and mortality among cancers of the female reproductive system, and initial surgical treatment is still one of the main treatments. However, for many years, radical hysterectomy based on traditional anatomical principles has failed to substantially improve oncological outcomes for cervical cancer patients or reduce the incidence of perioperative complications. In recent years, radical surgery grounded in the membrane anatomy concept of embryonic development has demonstrated promising oncological outcomes in colorectal cancer surgery. Research in the field of cervical cancer, however, remains in its early stages, although it is steadily garnering increased attention. Consequently, this meta-analysis seeks to systematically assess the safety and efficacy of radical hysterectomy, rooted in embryonic developmental principles, for the treatment of early-stage cervical cancer. METHODS:This study systematically searched PubMed, Embase, Cochrane Library, Web of Science, Wanfang, and CNKI databases for relevant studies published from their inception to October 2024. Data on 5-year recurrence-free survival (RFS), overall survival (OS), and surgical complications were collected for further analysis. RESULTS:Eight studies involving 1,226 patients were included in the meta-analysis. The surgical complication rate was 35.2%. Two studies reported a 5-year RFS of 86% and an OS of 88%. CONCLUSION:Radical hysterectomy based on embryo development-originated shows good safety and efficacy in treating early-stage cervical cancer. TRIAL REGISTRATION:PROSPERO Identifier: CRD42024602098.

Esophageal squamous cell carcinoma (ESCC) has high morbidity and mortality in developing countries. The purpose of this article is to study the mechanism of KLF5's effect on ESCC radiosensitivity. WGCNA gene expression profiling identified core genes associated with ESCC radiosensitivity. KLF5 expression was detected by RT-qPCR. The effects of overexpression or downregulation of KLF5 on anti-irradiated cells' proliferation, migration, invasion, and apoptotic activity were studied through colony formation assay, Transwell assay, and flow cytometry. Western blot can detect the activity of Nrf2 signaling pathway in cells and tissues. The enrichment of KLF5 at the Keap1 promoter was analyzed by ChIP-base, and the binding of KLF5 to Keap1 was analyzed by ChIP and dual-luciferase. They then injected ESCC cells into mice and used radiation to monitor tumor progression. KLF5 is a core gene in ESCC and is significantly associated with radiosensitivity. KLF5 expression is upregulated in drug-resistant ESCC cells. Overexpression of KLF5 significantly increased cell viability and attenuated cellular responses to radiation. KLF5 knockdown reduces radioresistance. After KLF5 overexpression, the Nrf2 signaling pathway was significantly up-regulated, and after KLF5 was up-regulated, the Keap1 signaling pathway was down-regulated. KLF5 inhibits the transcriptional activity of Keap1. Upregulation of Keap1 inhibits the effect of KLF5 overexpression on radioresistance of ESCC cells. KLF5/Keap1 regulates the effects of ESCC on in vivo radiotherapy. KLF5 promotes ESCC radioresistance by inhibiting Keap1 transcription and activating the Nrf2 pathway.

Objective: To explore the risk factors for lymph node metastasis in patients with cervical cancer, construct a risk prediction model for cervical cancer lymph node metastasis based on the FIGO 2018 staging system, and validate the model using both internal and external datasets. This model aims to provide a simple and effective tool for the clinical assessment of lymph node metastasis risk in cervical cancer patients. Methods: A total of 5787 patients with pathologically confirmed cervical cancer from the SEER database, diagnosed between 2000 and 2021, were selected. The patients were randomly divided into a training group and an internal validation group in a 7:3 ratio using R software. Univariate and binary logistic regression analyses were employed to identify independent factors affecting lymph node metastasis in cervical cancer patients. A nomogram prediction model was developed based on the selected factors. The model's performance was evaluated using receiver operating characteristic curves and calculating the area under the curve , along with calibration curves. The Hosmer-Lemeshow goodness-of-fit test and Spiegelhalter Z test were used to assess model performance. Additionally, an external validation cohort consisting of 338 cervical cancer patients treated at our institution between January 2019 and December 2024 was used for receiver operating characteristic curve and calibration curve validation. Results: A total of 5787 cervical cancer patients from the SEER database were included, with 4051 patients in the training group and 1736 patients in the internal validation group. Among these, 729 patients (18.00%) in the training group and 312 patients (17.97%) in the internal validation group had lymph node metastasis. Univariate analysis revealed that histologic type, tumor stage and grade, and tumor size were significantly associated with lymph node metastasis in cervical cancer (P < 0.05). Binary logistic regression analysis identified age, histologic type, tumor stage and grade, and tumor size as factors significantly related to lymph node metastasis in cervical cancer (P < 0.001). The nomogram model based on these variables showed an AUC of 0.758 (95% CI: 0.739–0.776) in the training group, 0.753 (95% CI: 0.726–0.781) in the internal validation group, and 0.742 (95% CI: 0.678–0.805) in the external validation group, indicating good discrimination and stability of the model. The Hosmer-Lemeshow test for the training and internal validation groups both yielded P values > 0.05, and the Spiegelhalter Z test for the external validation group yielded a P value of 0.0989. Calibration curves showed good agreement between predicted probabilities and actual observed outcomes, suggesting excellent model fit. Conclusion: The FIGO 2018-based risk prediction model for lymph node metastasis in cervical cancer, developed using the SEER database, demonstrates high predictive accuracy and strong clinical applicability. This model provides an effective reference for the precise preoperative assessment of lymph node metastasis risk in cervical cancer patients.