Integrin alpha 6 (ITGA6) has been implicated in tumorigenesis and progression, but its roles across cancer types and its functional significance in uveal melanoma (UVM) remain incompletely characterized. We performed an integrated pan-cancer analysis of ITGA6 expression, diagnostic performance, prognostic relevance, immune associations, pathway activity, and drug sensitivity. In addition, we evaluated its functional role in UVM using in vitro assays, including proliferation, migration, invasion, and colony formation experiments following ITGA6 knockdown. ITGA6 was upregulated in multiple tumor types, including lung squamous cell carcinoma and hepatocellular carcinoma. Diagnostic analysis indicated strong discriminatory value in several cancers, with AUC values > 0.95 in pheochromocytoma/paraganglioma and cholangiocarcinoma, and AUC values of 0.85–0.95 in pancreatic adenocarcinoma, hepatocellular carcinoma, kidney chromophobe, and head and neck squamous cell carcinoma. Survival analyses revealed that the prognostic association of ITGA6 was cancer-type dependent: higher ITGA6 expression correlated with better outcomes in skin cutaneous melanoma and uterine corpus endometrial carcinoma, but with worse outcomes in lung adenocarcinoma, lower-grade glioma, and UVM. In UVM, elevated ITGA6 expression was associated with poorer overall survival, progression-free interval, and disease-specific survival, and was positively correlated with immune infiltration and malignant functional states. ITGA6 expression showed positive correlations with all 14 functional state gene sets in UVM, with particularly strong correlations for angiogenesis, proliferation, and stemness. Pathway analyses further suggested that high ITGA6 expression was associated with epithelial-mesenchymal transition and TNF-α/NF-κB signaling. Drug sensitivity analyses identified several compounds that may be associated with ITGA6-related transcriptional signatures. Functional experiments showed that ITGA6 knockdown significantly inhibited proliferation, migration, invasion, and colony formation in UVM cells. These findings suggest that ITGA6 may serve as a potential diagnostic and prognostic biomarker in selected cancers and support a tumor-promoting role for ITGA6 in UVM.

Background:The immunological interaction between the lung and gut remains underexplored, particularly in the context of coexisting mucosal inflammation. While IL-17A has been implicated in both asthma and colitis independently, its role in coordinating systemic immune responses across tissue compartments is not well defined. Methods:In this study, we developed a combined house dust mite-induced asthma model and dextran sulfate sodium-induced colitis model to investigate the role of IL-17A in driving inflammation in both the lungs and the intestines. Results:Our findings demonstrate that IL-17A neutralization markedly reduced airway and intestinal inflammation, attenuated mucus hypersecretion, downregulated pro-inflammatory cytokine expression, and alleviated colitis severity. Histopathological analysis revealed decreased infiltration of immune cells, including eosinophils, lymphocytes, and macrophages, in both the lungs and colonic tissues following IL-17A blockade. Additionally, we observed a reduction in mucus production, particularly in the airways, highlighting IL-17A's direct role in mucin regulation. Transcriptomic analysis confirmed that IL-17A blockade downregulated several immune-related pathways in colon tissues, further supporting its central role in mediating multi-organ inflammation. Conclusion:These findings indicate that IL-17A represents a systemic immunomodulator, which orchestrates compartmentalized immune responses along the lung-gut axis. The observed tissue-specific redistribution of IL-17A and the therapeutic benefit of its neutralization suggest that IL-17A may serve as a clinically actionable target in patients with overlapping asthma and colitis. The study also shows that IL-17A plays a reciprocal role in influencing immune responses in both lung and gut.

Notch signaling is a widely preserved communication pathway that supports essential cellular functions by allowing adjacent cells to interact. The Notch signaling pathway consists of Notch ligands (DSL proteins), Notch receptors, DNA-binding proteins, and downstream target genes. Hepatocellular carcinoma (HCC) represents the predominant cause of cancer-related deaths globally and poses a significant threat to human health. For highly malignant HCC, current treatment options, including chemotherapy, radiotherapy, immunotherapy, targeted therapies, and surgical procedures, often have poor prognoses. Therefore, there is a need to explore additional therapeutic strategies. Many studies have found that abnormal activation of the Notch signaling pathway contributes to tumor initiation and progression by promoting HCC proliferation, metastasis, stem cell-like properties, and drug resistance. In this research, we reveal the composition and activation mechanisms of the Notch signaling pathway, as well as the molecular mechanism underlying its aberrant activation in HCC. Furthermore, we summarize recent advances in targeting Notch signaling for the treatment of HCC. This review aims to highlight the promising potential of investigating the Notch pathway as a therapeutic target in HCC.

Introduction: Sepsis-related acute liver injury involves complex immune dysfunctions. Epoxyeicosatrienoic acids (EETs), bioactive molecules derived from arachidonic acid (AA) via cytochrome P450 (CYP450) and rapidly hydrolyzed by soluble epoxide hydrolase (sEH), possess anti-inflammatory properties. Nevertheless, the impact of the sEH inhibitor TPPU on sepsis-related acute liver injury remains uncertain. Objectives: This study utilized comprehensive single-cell analysis to investigate the immunoregulatory mechanism of TPPU in alleviating sepsis-related acute liver injury. Methods: Hepatic bulk RNA sequencing and proteomics analyses were employed to investigate the mechanisms underlying sepsis-related acute liver injury induced by cecal ligation and puncture in mice. Cytometry by time-of-flight and single-cell RNA sequencing were conducted to thoroughly examine the immunoregulatory role of TPPU at single-cell resolution. Results: Downregulation of AA metabolism and the CYP450 pathway was observed during sepsis-related acute liver injury, and TPPU treatment reduced inflammatory cytokine production and mitigated sepsis-related hepatic inflammatory injury. Comprehensive single-cell analysis revealed that TPPU promotes the expansion of anti-inflammatory CD206+CD73+ M2-like macrophages and PDL1-CD39-CCR2+ neutrophils, reprogramming liver neutrophils to an anti-inflammatory CAMP+NGP+CD177+ phenotype. Additionally, TPPU inhibits the CCL6-CCR1 signaling mediated by M2-like macrophages and CAMP+NGP+CD177+ neutrophils, altering intercellular communication within the septic liver immune microenvironment. Conclusion: This study demonstrated TPPU’s protective efficacy against sepsis-related acute liver injury, underscoring its vital role in modulating liver macrophages and neutrophils and enhancing prospects for personalized immunomodulatory therapy.

BACKGROUND:The long non-coding RNA PVT1 (lncRNA PVT1) has been reported to act as an oncogenic regulator of several cancers. However, its expression and function in gallbladder cancer (GBC) remain largely unknown. METHODS:In situ hybridization (ISH) and quantitative real-time PCR (qPCR) were performed to detect the expression of PVT1 and miR-143 in GBC tissues and cell lines. Immunohistochemistry (IHC) assays were performed to assess the expression of the hexokinase 2 (HK2) protein. The relationships among PVT1, miR-143 and HK2 were evaluated using dual-luciferase reporter, RNA immunoprecipitation (RIP) and biotin pull-down assays. The biological functions of PVT1, miR-143 and HK2 in GBC cells were explored with cell counting kit 8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation, transwell, wound healing and glucose metabolism assays in vitro. For in vivo experiments, a xenograft model was used to investigate the effects of PVT1 and HK2 on GBC. RESULTS:PVT1 was upregulated in GBC tissues and cells and was positively associated with malignancies and worse overall survival. PVT1 knockdown inhibited cell proliferation, migration, and invasion in vitro and restrained tumor growth in vivo. Further studies demonstrated that PVT1 positively regulated HK2 expression via its competing endogenous RNA (ceRNA) activity on miR-143. Additionally, HK2 expression and function were positively correlated with PVT1. Furthermore, we observed that the PVT1/miR-143/HK2 axis promoted cell proliferation and metastasis by regulating aerobic glucose metabolism in GBC cells. CONCLUSIONS:The results of our study reveal a potential ceRNA regulatory pathway in which PVT1 modulates HK2 expression by competitively binding to endogenous miR-143 in GBC cells, which may provide new insights into novel molecular therapeutic targets for GBC.

ObjectivesTo explore the value of cellular microstructural mapping by IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) method in evaluating the histological type and prognostic factors of rectal lesions.Materials and methodsSixty-six patients with rectal lesions were enrolled in this study. All subjects underwent MRI scans including conventional diffusion weighted imaging (DWI) and the IMPULSED MRI scans of oscillating gradient spin-echo (OGSE) and pulse gradient spin-echo (PGSE) sequences. Parameters including mean cell diameter (dmean), intracellular fraction (vin), extracellular diffusivity (dex), cellularity, and apparent diffusion coefficient (ADC) values (ADCPGSE, ADC17Hz, ADC33Hz, and ADC of conventional DWI) were measured in different histopathologic types, grades, stages, and structure invasion statuses. The receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic power. The sensitivity, specificity, and the corresponding area under the curves (AUCs) were calculated.ResultsOur preliminary results illustrated that malignant lesion showed higher vin and cellularity ([0.2867 ± 0.0697] vs. [0.1856 ± 0.1011], [2.3508 ± 0.6055] vs. [1.2716 ± 0.4574], all P<0.05), lower dex and ADC values (ADCPGSE, ADC17Hz, and ADC of conventional DWI) compared to benign lesion ([2.1637 ± 0.3303 μm2/ms] vs. [2.5595 ± 0.5085 μm2/ms], [0.9238 (0.7959, 1.0741) ×10-3 mm2/s] vs. [1.3373 ± 0.3902×10-3 mm2/s], [1.3204 ± 0.2342×10-3 mm2/s] vs. [1.8029 ± 0.3119×10-3 mm2/s], [0.7400 (0.6750, 0.8375) ×10-3 mm2/s] vs. [1.0550 ± 1.1191×10-3 mm2/s], all P<0.05), while no significant difference was seen for dmean. Vin and cellularity of rectal common adenocarcinoma (AC) were significantly higher than those of rectal mucinous adenocarcinoma (MC) ([0.2994 ± 0.0626] vs. [0.2028 ± 0.0571], [2.4579 ± 0.5553] vs. [1.6412 ± 0.4347], all P<0.05), while dex and ADC values (ADCPGSE, ADC17Hz, ADC33Hz, and ADC of conventional DWI) were lower in AC ([2.1189 ± 0.3187 μm2/ms] vs. [2.4609 ± 0.2534 μm2/ms], [0.8996 ± 0.1583×10-3 mm2/s] vs. [1.2072 ± 0.2326×10-3 mm2/s], [1.2714 ± 0.1916×10-3 mm2/s] vs. [1.6451 ± 0.2420×10-3 mm2/s], [1.8963 (1.6481, 2.1138) ×10-3 mm2/s] vs. [2.3104 ± 0.3851×10-3 mm2/s], [0.7341 ± 0.8872×10-3 mm2/s] vs. [1.1410 ± 0.1840×10-3 mm2/s], all P<0.05). In AC group, the dmean had significant difference between negative and positive tumor budding (TB) ([13.2590 ± 1.3255 μm] vs. [14.3014 ± 1.1830 μm], P<0.05). No significant difference of dmean, vin, dex, cellularity or ADC values was observed in AC with different grade, T stage, N stage, perineural and lymphovascular invasion (all P>0.05). The ROC curves showed that the area under the curves (AUCs) of vin, dex, cellularity, and ADC values (ADCPGSE, ADC17Hz, and ADC of conventional DWI) for distinguishing malignant and benign lesion were 0.803, 0.757, 0.948, 0.807, 0.908 and 0.905, respectively. The AUCs of vin, dex, cellularity, and ADC values (ADCPGSE, ADC17Hz, ADC33Hz, and ADC of conventional DWI) in distinguishing AC from MC were 0.887, 0.802, 0.906, 0.896, 0.896, 0.781 and 0.991, respectively. The AUC of the dmean for evaluating TB status was 0.726. The AUC of ADC from conventional DWI for evaluating WHO grade was 0.739.ConclusionCellular microstructural mapping by the IMPULSED method has great potential in preoperative evaluation of rectal lesions. It could be helpful in differentiating malignant and benign lesions, distinguishing AC from MC, and in predicting the TB status.

Hepatocellular carcinoma (HCC) is a prevalent malignancy originating from hepatocytes and is characterized by high invasiveness and fatality. Dysregulation of microRNAs (miRNAs) is frequently observed during HCC progression. This study aimed to investigate the role of miR-518b in HCC cell malignancy and tumor growth. MiR-518b expression in HCC cells was measured by RT-qPCR. The proliferative, migratory and invasive capabilities of Hep3B and SNU-387 were assessed by colony formation, wound healing and transwell assays, respectively. RNA immunoprecipitation and luciferase reporter assays were utilized to verify the binding between miR-518b and its target gene, early growth response factor 1 (EGR1). Results revealed that miR-518b was highly expressed while EGR1 was downregulated in HCC cells. Knockdown of miR-518b significantly repressed cell proliferation, migration and invasion. Moreover, miR-518b bound to 3'untranslated region of EGR1 and negatively regulated its expression in HCC cells. EGR1 knockdown counteracted the inhibitory impact of miR-518b inhibition on malignant cell behaviors. In addition, the silencing of EGR1 activated the PI3K/AKT/mTOR signaling in HCC cells, while miR-518b depletion had the opposite effect. Importantly, the suppressive impact of miR-518b on the pathway was rescued by EGR1 knockdown. In vivo experiments demonstrated that inhibition of miR-518b suppressed HCC tumor growth, reduced EGR1 and Ki67 (a proliferation marker) expression, and inactivated the PI3K/AKT/mTOR signaling. In conclusion, miR-518b promotes HCC tumorigenesis by targeting EGR1 and regulating the PI3K/AKT/mTOR signaling pathway.

OBJECTIVES:To investigate the therapeutic effects and mechanisms of 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) in a mouse model of asthma. METHODS:SPF-grade BALB/c mice were randomly divided into 7 groups (n=8 each group): normal control group, ovalbumin (OVA) group, dimethyl sulfoxide+corn oil group, budesonide (BUD) group, and low, medium, and high dose 2,6-DMBQ groups. An asthma mouse model was established by OVA induction, followed by corresponding drug interventions. Non-invasive lung function tests were performed to measure airway hyperresponsiveness, and enzyme-linked immunosorbent assay was used to determine levels of interleukin (IL)-17, IL-10, and serum immunoglobulin E in bronchoalveolar lavage fluid. A cell counter was employed to detect eosinophil counts in bronchoalveolar lavage fluid, while hematoxylin-eosin staining and periodic acid-Schiff staining were used to assess lung tissue pathological changes. Western blot was conducted to examine the expression of proteins related to the mammalian target of rapamycin pathway (p-AKT/AKT and p-p70S6K/p70S6K), and a fully automated biochemical analyzer was used to evaluate liver and kidney functions. RESULTS:Compared with the normal control group, the OVA group showed increased enhanced pause values, inflammation scores from hematoxylin-eosin staining, positive area from periodic acid-Schiff staining, percentage of eosinophils, IL-17/IL-10 ratio, serum immunoglobulin E levels, and relative expression levels of p-AKT/AKT and p-p70S6K/p70S6K (P<0.05). The BUD group and the medium and high dose 2,6-DMBQ groups exhibited decreased values for these indicators compared to the OVA group (P<0.05). CONCLUSIONS:2,6-DMBQ can inhibit the mTOR pathway to alleviate airway inflammation in asthmatic mice, possibly by mitigating the imbalance between Th17 and regulatory T cells.

Gastric intestinal metaplasia (GIM) is a precancerous lesion and the key risk factor in the development of gastric cancer (GC), but early detection and treatment remain challenging. The traditional endoscopic diagnosis of metaplastic lesions is complicated by an increased rate of inappropriateness and false negativity. Although early interventions with H. pylori eradication, as well as endoscopic therapy results, were promising, there is still a significant unmet need to control GIM progression and recurrences. Molecular alterations, such as an increased DNA methylation index, have been identified as a crucial factor in the downregulation of tumor suppressor genes, such as the caudal-type homeobox (CDX2) gene, which regulates epithelial cell proliferation and GIM progression and is associated with treatment failure. CDX2 is downregulated by promoter hypermethylation in the colonic-type epithelium, in which the methylation was correlated with reduced intake of dietary folate sources. Tumor cells alter to dietary methionine sources in the biosynthesis of S-Adenosylmethionine, a universal methyl donor for transmethylation, under the conditions of limited folate and B12 availability. The gut microbiota also exhibited a shift in microbial composition, which could influence the host’s dietary methionine metabolism. Meanwhile, activated oncogenic signaling via the PI3K/Akt/mTORC1/c-MYC pathway could promotes rewiring dietary methionine and cellular proliferation. Tumor methionine dependence is a metabolic phenotype that could be helpful in predictive screening of tumorigenesis and as a target for preventive therapy to enhance precision oncology. This review aimed to discuss the molecular alterations in GIM to shed light on the alteration of methionine metabolism, with insight into new diagnostic and treatment approaches and future research directions.

Gastric signet ring cell carcinoma (GSRCC) is a distinct subtype of gastric cancer with unique epidemiological and pathogenic characteristics. However, its prognostic features and molecular landscape remain poorly understood, limiting the development of targeted therapies. In this study, we analyzed clinical data from over 10,000 patients with gastric cancer treated at Zhejiang Cancer Hospital between January 2010 and December 2019. A comprehensive proteomic analysis was conducted on 112 GSRCC patients with a signet ring cell content exceeding 70%, identifying 7322 proteins. This study established a tissue-specific peptide spectral library, representing the most extensive proteomic atlas of GSRCC to date. We identified four novel proteomic subtypes: metabolism, microenvironment dysregulation, migration, and proliferation. Furthermore, PRDX2 and DDX27 emerged as potential prognostic biomarkers, which were further validated in an independent cohort of 75 patients. Molecular profiling of 79 cases that lacked expression of established gastric cancer treatment targets and biomarkers revealed significant tumor heterogeneity. Unsupervised clustering identified three distinct proteomic clusters, with cluster 2 exhibiting the poorest prognosis. Additionally, we identified four potential drug targets, including PFAS, EIF2S3, EIF6, and NFKB2. Molecular docking analysis suggested that neratinib, a clinically approved drug, could serve as a promising therapeutic agent for GSRCC, offering new avenues for clinical intervention.

Background:Neuroblastoma (NB) is a common malignancy in children, and accurate risk stratification and prognostic assessment are essential for personalized treatment. Current tumor assessment methods rely on clinical features and conventional imaging techniques, which have limited predictive accuracy. The aim of this study was to develop a deep learning model based on multiphase enhanced CT images and clinical features to improve the accuracy of risk stratification and prognostic assessment of NB. Methods:Multi-phase enhanced CT images and clinical features from 202 NB patients were collected. Four risk stratification classifiers were developed using the Swin Transformer model and evaluated in training and testing cohorts. Prognostic models were constructed using a combination of multiple machine learning algorithms in conjunction with CT image features and clinical characteristics. Results:Swin-ART based on arterial phase images was the best risk stratification classifier with an AUC of 0.770 (95% CI: 0.613-0.909) and an accuracy of 0.780 in the testing cohort. In the prognostic assessment, the combined model of backward stepwise Cox regression and randomized survival forest (RSF) obtained the highest mean C-index of 0.84. The 1-, 3-, and 5-year AUC values of the optimal prognostic model in the training cohort were 0.93 (95% CI: 0.927-0.942), 0.93 (95% CI: 0.929-0.946), and 0.96 (95% CI: 0.953-0.974), respectively. The corresponding AUC values for the testing cohort were 0.90 (95% CI: 0.857-0.934), 0.87 (95% CI: 0.808-0.928), and 0.91 (95% CI: 0.718-0.977), respectively. Multimodal models outperform single-modality clinical models in both predictive accuracy and stability. Conclusion:This study successfully developed a deep learning model based on multiphase enhanced CT images and clinical features to predict risk stratification and prognosis in NB. The findings provide a new tool for clinical practice and lay the foundation for future precision medicine and personalized treatment.

Background Hepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis‑related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC. Methods The data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan–Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman’s rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2). Results We identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells. Conclusions The DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC.

Digestive system cancers rank among the most prevalent malignant tumors, maintaining persistently high incidence and mortality rates. Notch signaling activity, often aberrant in esophageal, gastric, hepatic, pancreatic, and colorectal cancers, plays a pivotal role in the initiation, progression, and therapy resistance of these malignancies. As a highly conserved pathway, Notch signaling is integral to cell differentiation, survival, proliferation, stem cell renewal, development, and morphogenesis. Its dysregulation has been increasingly linked to various diseases, particularly digestive system cancers. In these malignancies, altered Notch signaling influences multiple biological processes, including cell proliferation, invasion, cell cycle progression, immune evasion, drug resistance, and stemness maintenance. Understanding the mechanisms of Notch signaling in digestive system cancers is essential for the development of novel targeted therapies. Numerous Notch pathway-targeting drugs are currently in preclinical studies, demonstrating promising efficacy both as monotherapies and in combination with conventional anti-cancer treatments. This review summarizes recent high-quality findings on the involvement of Notch signaling in digestive system cancers, focusing on the expression changes and pathological mechanisms of its dysregulated components. Special emphasis is placed on the potential of translating Notch-targeted approaches into therapeutic strategies, which hold promise for overcoming the limitations of existing treatments and improving the poor prognosis associated with these cancers.

The long non-coding RNA taurine up-regulated gene 1 (TUG1) has been reported to be involved in various cancers, but its role in chondrosarcoma (CHS) remains a mystery. This research aimed to examine the function of TUG1 in CHS. We found that TUG1 expression was elevated in CHS. Functional assays demonstrated that TUG1 had a crucial role in the CHS cell progression. Mechanistically, TUG1 recruited ALYREF to maintain the stabilization of enhancer of zest homolog 2 (EZH2) mRNA and expression of H3K27me3, repressing the transcription of the tumor-suppressor gene CPEB1. Additionally, exosomal TUG1 enhanced the polarization of M2 tumor-associated macrophages, which increased the proliferation and metastasis of CHS. Taken together, this study revealed the oncogenic role of TUG1 in CHS and its interactions with the downstream regulatory axis, offering novel insights into the tumorigenic mechanism of CHS.

Hepatocellular carcinoma (HCC) is the fourth leading cause of malignancy worldwide, and its progression is influenced by the immune microenvironment. Natural killer (NK) cells are essential in the anti-tumor response and have been linked to immunotherapies for cancers. Therefore, it is important to unify and validate the role of NK cell-related gene signatures in HCC. In this study, we used RNA-seq analysis on HCC samples from public databases. We applied the ConsensusClusterPlus tool to construct the consensus matrix and cluster the samples based on their NK cell-related expression profile data. We employed the least absolute shrinkage and selection operator regression analysis to identify the hub genes. Additionally, we utilized the CIBERSORT and ESTIMATE web-based methods to perform immune-related evaluations. Our results showed that the NK cell-related gene-based classification divided HCC patients into three clusters. The C3 cluster was activated in immune activation signaling pathways and showed better prognosis and good clinical features. In contrast, the C1 cluster was remarkably enriched in cell cycle pathways. The stromal score, immune score, and ESTIMATE score in C3 were much higher than those in C2 and C1. Furthermore, we identified six hub genes: CDC20, HMOX1, S100A9, CFHR3, PCN1, and GZMA. The NK cell-related genes-based risk score subgroups demonstrated that a higher risk score subgroup showed poorer prognosis. In summary, our findings suggest that NK cell-related genes play an essential role in HCC prognosis prediction and have therapeutic potential in promoting NK cell antitumor immunity. The six identified hub genes may serve as useful biomarkers for novel therapeutic targets.

The current study aimed to explore the feasibility of readout-segmented echo-planar imaging (RS-EPI) of the testis at 3.0 T, by comparing with single-shot echo-planar imaging (SS-EPI) in qualitative image quality and quantitative apparent diffusion coefficient (ADC) values. 66 patients undergoing scrotal MRI for various clinical indications were included retrospectively. RS-EPI image quality was rated from 1 (severe distortion or artifact, or nondiagnostic) to 4 (nearly no distortion or artifact, or outstanding). The comparative image quality (RS- vs. SS-EPI) was rated from − 2 (SS-EPI severe or greater conspicuity) to 2 (RS-EPI severe or greater conspicuity). The confidence interval of proportions (CIOP) of comparative image quality and Wilcoxon rank sum test were performed to assess the preferences between RS-EPI and SS-EPI. Paired samples t-test and Bland–Altman analysis were performed to compare the mean ADC values of RS-EPI and SS-EPI. The mean, maximum, and minimum ADC values measured by RS-EPI were compared in normal testicular parenchyma, benign and malignant intratesticular lesions. The evaluation of RS-EPI image quality showed RS-EPI with the characteristics of slight geometric distortion and susceptibility artifact, and good lesion conspicuity. The assessment of comparative image quality showed SS-EPI with obvious geometric distortion and susceptibility artifact, and RS-EPI preferred in lesion conspicuity. The CIOP ranged from 97 to 100% among three readers, with preferring to RS-EPI improving image quality (P < 0.001). There was a strong correlation and good agreement between mean ADC values measured by RS-EPI and SS-EPI. The mean, maximum and minimum ADC values by RS-EPI were significantly different in normal testicular parenchyma, benign and malignant intratesticular lesions. RS-EPI DWI of the testis improved image quality in geometric distortion, susceptibility artifacts, and lesion conspicuity, and provided highly correlated and consistent mean ADC values when compared to SS-EPI DWI, indicating the feasibility of RS-EPI DWI of testes.