AIMS:This study aimed to compare the safety and effectiveness of cone-beam CT (CBCT)-guided thermal ablation vs video-assisted thoracic surgery (VATS) in patients with stage I-IIIA non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS:A total of 43 NSCLC patients underwent CBCT-guided thermal ablation, and 899 patients received VATS. After 1:1 propensity score matching (PSM), 32 patients were included in each cohort. Overall survival (OS), disease-free survival (DFS), recurrence rates, length of hospital stay, and complications were analyzed. RESULTS:The mean OS was 3.02 ± 1.31 years in the ablation group and 4.79 ± 2.87 years in the VATS group ( P = 0.08). The mean DFS was 2.30 ± 1.55 years and 4.34 ± 2.98 years, respectively ( P = 0.021). Local and distant recurrence occurred in five (15.6%) and seven (21.9%) patients in the ablation group, and in six (18.8%) and seven (21.9%) patients in the VATS group, with no significant difference in overall recurrence ( P = 0.595). The hospital stay was significantly shorter in the ablation group (3.67 ± 2.04 days) than in the VATS group (8.21 ± 3.68 days, P < 0.0001). The incidences of pneumothorax (P = 0.430), infection ( P = 0.086), pneumonia ( P = 0.554), and fever ( P = 0.230) were comparable between groups. CONCLUSION:CBCT-guided thermal ablation is a safe and effective treatment option for patients with stage I-IIIA NSCLC.

Abstract Lysine lactylation is a dynamic post-translational modification that can alter protein function and has been implicated in diverse physiological and pathological processes. Accurate identification of lactylation sites is therefore important for defining its regulatory landscape and for generating testable hypotheses about lactylation-associated mechanisms. Here, we introduce CLEAR-Lactyl and AttentionKla. CLEAR-Lactyl is a curated benchmark dataset of human lysine lactylation comprising 16,604 positive sites. AttentionKla is a deep learning framework trained on CLEAR-Lactyl that employs a pre-trained protein language model fine-tuned with LoRA; it significantly outperforms existing tools, and the factors contributing to its performance gain have been dissected through comprehensive ablation studies. Its utility in predicting novel lactylation sites and in sequence-directed modulation of lactylation levels has been experimentally validated in cellular assays. Together, CLEAR-Lactyl and AttentionKla provide a powerful platform for lysine lactylation research and offer an extensible framework for the precise modulation of other post-translational modifications.

A nuclear protein in testis (NUT) carcinoma is a rare, aggressive malignancy often diagnosed late due to non-specific symptoms and low awareness. A 69-year-old woman presented with haemoptysis and a positron emission tomography-avid lung nodule (cT1N0M0). An initial bronchoscopic biopsy suggested small cell carcinoma with negative NUT staining. Following a lobectomy, immunohistochemical analysis showed strong nuclear NUT positivity, and fluorescence in situ hybridization confirmed NUT rearrangement. This case was atypical due to the patient's age, early stage, and initial misdiagnosis from a limited biopsy. The non-specific presentation of an NUT carcinoma requires a high degree of suspicion, and small biopsies risk a misdiagnosis.

e16261 Background: Gemcitabine plus cisplatin remains the standard first-line therapy for advanced biliary tract cancers (BTCs). However, disease progression within 8 months in most patients underscores the critical unmet need for effective second-line therapies. Compared to traditional irinotecan, the liposomal irinotecan offers a superior therapeutic profile characterized by higher efficacy and lower toxicity. The combination of liposomes irinotecan with capecitabine(a standard treatment) is currently being explored as a novel therapeutic option in ongoing clinical studies. Methods: This multicenter, single-arm, phase II trial enrolled patients with advanced BTCs (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer) who had progressed on first-line gemcitabine-based therapy. Patients received the combination of liposomal irinotecan and capecitabine. Treatment continued until disease progression. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS) and safety. Results: Between April 2024 and November 2025, 20 patients were enrolled and treated. The median age was 62.5 years (51-74), and 65% were male (13/20). Tumor types included extrahepatic cholangiocarcinoma (20%), intrahepatic cholangiocarcinoma (40%), and gallbladder cancer (40%). The combination therapy demonstrated promising efficacy, with a median PFS (mPFS) of 5.5 months（95%CI [4.50-NA]）. And the longest duration of continuous treatment observed was 14.1 months. which compares favorably to historical benchmarks in this setting. Of the 14 evaluable patients, 3 (21.4%) achieved a partial response, 8 (57.2%) maintained stable disease, and 3 (21.4%) experienced progressive disease. The ORR was 21.4%. Treatment was well-tolerated, with a 30% incidence of grade≥3 treatment-related adverse events (TRAEs). Including decreased white blood cell count(5.0%), neutropenia(10.0%) and diarrhea(5.0%). No fatal TRAEs were observed. Conclusions: The regimen of liposomal irinotecan plus capecitabine showed encouraging anti-tumor activity with a manageable safety profile in patients with gemcitabine-pretreated advanced BTCs, suggesting a potential new therapeutic option for the second-line setting. The follow-up work on patient survival is underway, and more data will be disclosed in the future. Clinical trial information: NCT06430827 .

Ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, is associated with chemoresistance in lung adenocarcinoma (LUAD). This study aims to investigate the role of sarcosine in ferroptosis and its underlying mechanisms. An RSL3-induced ferroptosis model was used to screen a library of 889 human endogenous metabolites and metabolomic profiling was harnessed to identify metabolites associated with ferroptosis. Cell viability, lipid-reactive oxygen species (ROS), ferrous iron, malondialdehyde (MDA), and mitochondrial integrity were assessed to evaluate sarcosine’s effects on ferroptosis. Metabolic fate was studied using 15N-labeled sarcosine. Next, we used untargeted metabolomic profiling and next-generation sequencing to dissect metabolic and transcriptomic changes upon sarcosine supplementation. The effects of sarcosine on ferroptosis and chemotherapy were further validated in patient-derived organoids (PDOs), xenograft models, and LUAD tissues. Sarcosine emerged as a potent ferroptosis inducer in the metabolic library screening, which was further confirmed via cell viability, lipid-ROS, ferrous iron, and MDA measurements. Metabolic flux analysis showed limited conversion of sarcosine to other metabolites in LUAD cells, while untargeted metabolomic profiling and seahorse assays indicated a metabolic shift from glycolysis to oxidative phosphorylation. Sarcosine enhanced pyruvate dehydrogenase activity to generate more ROS by interacting with PDK4, reducing PDHA1 phosphorylation. As a co-activator of N-methyl-D-aspartate receptor (NMDAR), sarcosine also exerted its pro-ferroptosis effect via regulating ferrous export through the NMDAR/MXD3/SLC40A1 axis. Given the significance of ferroptosis in chemotherapy, we validated that sarcosine enhanced the sensitization of cisplatin by promoting ferroptosis in LUAD cells, PDOs, and xenograft models. Sarcosine promotes ferroptosis and enhances chemosensitivity, suggesting its potential as a therapeutic agent in treating LUAD.

Background: With the wide application of lung cancer screening, the detection rate of multiple pulmonary nodules (MPNs) has increased annually. However, the optimal therapeutic strategy for MPNs has not achieved a consensus. This study aims to report a novel hybrid technique for the treatment of MPNs. Methods: A total of 8 patients received CT-guided lung microwave ablation combined with video-assisted thoracic surgery from March 2020 to March 2023. Three-dimensional reconstruction was conducted to distinguish the precise localization, predict the resection extent, and conduct the optimal operation procedure for each lung nodule. The clinicopathological characteristics as well as surgical complications and short-term outcomes were recorded. Results: 8 patients with a total of 18 nodules were treated by our hybrid technique. Two patients had a FEV1％ Pred lower than 90％. The nodules treated by surgery were confirmed as malignant by pathological results with a median size of 9mm.The median size of the nodules treated by ablation was 6mm. The median ablation power used for the nodules was 45 W (range, 40–50W). The ablation time was 5min. The median distance between nodules to pleura was 31mm (range 19-56mm). This hybrid technique did not increase the rate of complication and prolonged hospital stay. During the short term of follow-up, no recurrence occurred in the patients. Conclusions: We present our experience of percutaneous lung ablation combined with video-assisted thoracic surgery guided by three-dimensional reconstruction in the treatment of multiple pulmonary nodules. This technique provides a minimally invasive and personalized therapy for patients with MPNs.

The development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment represents a significant challenge to targeted therapies for lung cancer. To explore the feasibility of epigenetic therapy in overcoming resistance, an epigenetic drug library was screened, identifying Remodelin as a potent enhancer of EGFR-TKI sensitivity in non-small cell lung cancer (NSCLC) cells. We demonstrated that the cytidine acetyltransferase NAT10 was overexpressed in NSCLC tissues and was associated with poor patient prognosis. NAT10 knockdown inhibited proliferation, increased apoptosis, and enhanced sensitivity to EGFR-TKIs both in vitro and in vivo. Mechanistically, NAT10 promoted EGFR-TKI resistance in NSCLC by remodeling fatty acid metabolism. Specifically, NAT10 was found to promote ac4C modification of fatty acid transport protein 4 (FATP4) and carnitine palmitoyltransferase 1 A (CPT1A) mRNAs, leading to increased stability and expression of these genes. Furthermore, p300-mediated H3K27ac acetylation was found to be a critical upstream regulator of NAT10 transcription. In vivo, mouse xenograft models confirmed that Remodelin significantly enhanced the antitumor efficacy of gefitinib. These findings suggest the potential of NAT10 as a therapeutic target to overcome EGFR-TKI resistance and improve treatment outcomes in patients with NSCLC.

Current understanding of neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) lacks high-level evidence. This study provides additional efficacy data for this treatment regimen. Clinical trials investigating neoadjuvant tislelizumab plus chemotherapy in locally advanced ESCC were identified through literature search. Raw data from investigators were pooled for analysis. Primary endpoint was pCR; secondary endpoints included MPR, R0 resection rate, EFS, DFS, and OS. Six studies involving 306 patients were analyzed; 275 (89.9

Retinol, a pivotal regulator of cellular growth and apoptosis, has garnered substantial attention for its intricate involvement in cancer development. To explore Vitamin A's impact on lung adenocarcinoma (LUAD), we utilized comprehensive datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to dissect the intricate role of retinol in cancer progression. The unsupervised clustering analysis, grounded on retinol metabolism gene sets, divided patients into two distinct clusters, with cluster 1 exhibiting significantly inferior survival outcomes. Through differential analysis, we uncovered 349 differentially mutated and 394 differentially expressed genes between these clusters. Leveraging these discoveries, we built a seven-gene signature model that precisely predicted poorer survival for patients with a higher risk score, which was subsequently validated in four independent GEO cohorts, demonstrating its robustness and reliability. Our drug sensitivity analysis further revealed that high-risk patients were more susceptible to gefitinib and erlotinib. Notably, leveraging gene dependency scores and RNA-seq data from LUAD cell lines, we identified Phosphoribosylaminoimidazole Carboxylase And Phosphoribosylaminoimidazolesuccinocarboxamide Synthase (PAICS) as a potential therapeutic target. Single-RNA sequencing confirmed PAICS's predominant expression in cancer cells, and functional assays underscored its oncogenic role in promoting cell proliferation, migration, and invasion. These novel findings offer profound insights into potential therapeutic avenues for LUAD patients with poor prognoses, paving the way for future research endeavors.

Ferroptosis is a regulated cell death driven by iron-dependent lipid peroxidation and associated with drug resistance in lung adenocarcinoma (LUAD). It’s found that aldehyde dehydrogenase 2 (ALDH2), which is highly mutated in East Asian populations, is correlated with response to chemotherapy in LUAD patients. The rs671 variant knock-in, downregulation, and pharmacological inhibition of ALDH2 render LUAD cells more vulnerable to ferroptosis inducers and platinum-based chemotherapy. ALDH2 inhibits ferroptosis through the detoxification of 4-hydroxynonenal and malondialdehyde, the product of lipid peroxidation, as well as the production of NADH at the same time. Besides, ALDH2 deficiency leads to elevated intracellular pH (pHi), thus inhibiting the ERK/CREB1/GPX4 axis. Interestingly, ALDH2 is also regulated by CREB1, and the ALDH2 enzyme activity was decreased with elevated pHi. What’s more, the elevated pHi caused by impaired ALDH2 activity promotes the biosynthesis of lipid droplets to counteract ferroptosis. At last, the effect of ALDH2 on ferroptosis and chemosensitivity is confirmed in patient-derived organoids and xenograft models. Collectively, this study demonstrates that ALDH2 deficiency confers sensitivity to platinum through ferroptosis in LUAD, and targeting ALDH2 is a promising new strategy to enhance the sensitivity of platinum-based chemotherapy for the treatment of LUAD patients.

KRAS is among the most commonly mutated oncogenes in human malignancies. Although the advent of sotorasib and adagrasib, has lifted the "undruggable" stigma of KRAS, the resistance to KRAS inhibitors quickly becomes a major issue. Here, we reported that aldehyde dehydrogenase 1 family member A1 (ALDH1A1), an enzyme in retinoic acid biosynthesis and redox balance, increases in response to KRAS inhibitors and confers resistance in a range of cancer types. KRAS inhibitors' efficacy is significantly improved in sensitive or drug-resistant cells, patient-derived organoids (PDO), and xenograft models by ALDH1A1 knockout, loss of enzyme function, or inhibitor. Furthermore, we discovered that ALDH1A1 suppresses the efficacy of KRAS inhibitors by counteracting ferroptosis. ALDH1A1 detoxicates deleterious aldehydes, boosts the synthesis of NADH and retinoic acid (RA), and improves RARA function. ALDH1A1 also activates the CREB1/GPX4 pathway, stimulates the production of lipid droplets in a pH-dependent manner, and subsequently prevents ferroptosis induced by KRAS inhibitors. Meanwhile, we established that GTF2I is dephosphorylated at S784 via ERK by KRAS inhibitors, which hinders its nuclear translocation and mediates ALDH1A1's upregulation in response to KRAS inhibitors. In summary, the results offer valuable insights into targeting ALDH1A1 to enhance the effectiveness of KRAS-targeted therapy through ferroptosis in cancer treatment.

e14661 Background: Response of neoadjuvant immunotherapy can vary among patients in locally advanced ESCC, with the lack of a promising biomarker which need fully capture the heterogeneity of TME. Now, based on final results of the SEEK-01 study (2023 ASCO, P#4047), we have, for the first time, established a precise correlation from baseline TME to pathological response, baseline LN status, and 1-year EFS. Methods: In SEEK-01 study, 22 locally advanced ESCC patients (cT2-4NxM0) were enrolled. Following neoadjuvant chemotherapy (paclitaxel-albumin+carboplatin) combined with tislelizumab, patients underwent minimal invasive esophagectomy (MIE). Fresh tumor tissues were obtained via endoscopy prior to neoadjuvant therapy for scRNAseq analysis. Pathological response was evaluated using the irRVT score, leading to classification into pCR (irRVT=0%), MPR (060%). Baseline LN status was determined based on pathological diagnosis after surgery. We identified subclusters of tumor-associated myeloid cells and stroma cells that significantly predicted pathological response, baseline LN metastasis and recurrence within 1 year. Prediction model of efficacy for neoadjuvant immunotherapy was developed using baseline expression ratios of differential subclusters. Results: Among 22 enrolled patients, 18 completed neoadjuvant therapy and MIE. 4 achieved pCR, 2 got MPR and 6 were non-responder. 12 of 18 proved baseline LN metastasis. 5 of 18 suffered recurrence within 1 year. Myeloid cells, cancer-associated fibroblast (Caf) and endothelium (Endo) shew heterogeneity that can predict pathological response, baseline LN metastasis or recurrence within 1 year. Upgrade of CXCL9+ tumor-associated-macrophage (TAM), LAMP3+mregDC3 was a strong predictor of pCR, while the upgrade of STAT1+TAM, C1q+TAM, IL1b+TAM, IL1b+ Neutrophil, C1q+ Neutrophil was a solid biomarker of non-responder. Besides, presence of PTGS1+Caf, RGS5+Caf, S100B+Caf, RND1+Endo and S100+Endo highly correlated with baseline LN metastasis and recurrence within 1 year, which was better than PET-CT. On this basis, we constructed predictive models for pathological response. With further validated by public scRNAseq and TCGA database, it showed excellent predictive ability and robustness. Conclusions: The final results of the SEEK-01 study demonstrate the differential baseline infiltration of myeloid cells that can predict pathological response of neoadjuvant immunotherapy. The characteristic changes in Caf and Endo in TME can predict occult LN metastasis and 1-year EFS. A predictive model for efficacy of neoadjuvant immunotherapy in locally advanced ESCC was developed to facilitate individualized and precise neoadjuvant therapy before treatment. Clinical trial information: NCT05807542 .

4047 Background: Neoadjuvant immunotherapy and chemotherapy have shown promise in improving outcomes for patients with locally advanced ESCC, but the response to treatment can vary among patients. Therefore, there is a need to identify predictive biomarkers that can guide treatment decisions and improve patient outcomes. The infiltration of immune cells within the tumor microenvironment has been shown to be an important factor in cancer progression and response to treatment. In this study, we sought to explore the immune microenvironment prospectively related to treatment response of Neoadjuvant immunotherapy by scRNAseq. Methods: This was a single-arm phase II clinical trial, planned to enroll 20 locally advanced ESCC patients (cT2-4N0-1M0). After neoadjuvant chemotherapy (paclitaxel-albumin + carboplatin) combined with tislelizumab, patients received minimal invasive esophagectomy (MIE).Prior to neoadjuvant therapy, fresh tumor tissues were obtained via endoscopy and used for scRNAseq analysis, to evaluate the predictive capacity of the immune microenvironment. Pathological outcomes were assessed and divided into pCR, MPR defined as <10% residual tumor excluding pCR, and non-MPR defined as >10%. Results: Out of 18 enrolled patients, 15 completed neoadjuvant therapy and MIE surgery since March 2022. Of these 15 patients, 3 achieved pCR, 2 got MPR, and 10 were non-MPR, with a total of 51,208 single cells sequenced. Both groups showed similarly low expression of PD-L1 (5.7% vs. 2.3%). Comparing pCR to non-MPR patients, the former showed a significant increase in T lymphocytes (CD8+(17.1% vs.1.1%), Regulatory T(20.2% vs.4.0%)), plasma cell(22.0% vs.8.3%), and mature dendritic cell(1.5% vs.0.5%); a significant decrease in B cells(0.9% vs. 1.9%), neutrophils(1.7% vs.11.0%), and tumor cell, as well as a similar expression of macrophage(5.6% vs.6.6%) and monocyte, indicating a clear difference in the immune cell infiltration landscape between two groups. Furthermore, we identified a new subtype of plasma cell which was highly enriched in the non-MPR group, even though the pCR group showed a great increase in plasma cells in total. Conclusions: This study demonstrates the heterogeneity of baseline immune cell infiltration landscape in Locally Advanced ESCC, in which pCR and non-MPR patients exhibited entirely different profiles, and provide a potential predictor of response to neoadjuvant immunotherapy. Our findings suggest that baseline immune cell infiltration status, rather than pd-L1 expression, could accurately predict pCR or non-MPR before treatment, which could guide personalizing and minimize the need for trial-and-error approaches.

Objective To analyze the difference in spectral characteristics between lung adenocarcinoma tumor profile and normal lung tissue by multispectral imaging（MSI） technology, and to explore its feasibility to quickly evaluate the invasive components of ground-glass nodular lung adenocarcinoma during operation. Methods This study was a prospective observational cohort study.Nine patients with lung adenocarcinoma diagnosed as pulmonary ground-glass nodules by chest CT in Zhongshan Hospital affiliated to Fudan University at August 2022 were selected. To explore the different characteristic spectral changes of ground-glass nodular lung adenocarcinoma with different proportion of infiltrating components, MSI was performed on the profiles of lung adenocarcinoma and peripheral normal lung tissue sections. Results Through profile MSI, it was found that lung adenocarcinoma had a characteristic three-peak elevation near the three characteristic absorption peaks of hemoglobin（420 nm, 540 nm, 580 nm） compared with normal lung tissue. It also showed characteristic elevation at 450-510 nm. With the increase of infiltrating components, the difference in hemoglobin content between the lung adenocarcinoma profile and the normal lung tissue profile increased. The spectral ratio curve of lung adenocarcinoma profile drawn based on normal lung tissue had three gradually increasing ratio peaks, and the relative height of the three ratio peaks could reflect the content of tumor infiltrating components. Conclusions The lung adenocarcinoma tumor profile with ground-glass nodules on imaging has characteristic spectral changes compared to the normal lung tissue profile. Quantifying the characteristic spectral changes can quickly predict the proportion of invasive components in lung adenocarcinoma lesions.

Background:N6-methyladenosine (m6A) RNA methylation plays a crucial role in important genomic processes in a variety of malignancies. However, the characterization of m6A with infiltrating immune cells in the tumor microenvironment (TME) in esophageal squamous carcinoma (ESCC) remains unknown.Methods:The single-cell transcriptome data from five ESCC patients in our hospital were analyzed, and TME clusters associated with prognosis and immune checkpoint genes were investigated. Cell isolation and qPCR were conducted to validate the gene characterization in different cells.Results:According to distinct biological processes and marker genes, macrophages, T cells, and B cells clustered into three to four different subgroups. In addition, we demonstrated that m6A RNA methylation regulators were strongly related to the clinical and biological features of ESCC. Analysis of transcriptome data revealed that m6A-mediated TME cell subsets had high predictive value and showed a close relationship with immune checkpoint genes. The validation results from qPCR demonstrated the characteristics of essential genes. CellChat analysis revealed that RNA from TME cells m6A methylation-associated cell subtypes had substantial and diversified interactions with cancer cells. Further investigation revealed that MIF- (CD74+CXCR4) and MIF- (CD74+CD44) ligand-receptor pairings facilitated communication between m6A-associated subtypes of TME cells and cancer cells.Conclusion:Overall, our study demonstrated for the first time the function of m6A methylation-mediated intercellular communication in the microenvironment of tumors in controlling tumor development and anti-tumor immune regulation in ESCC.

Ferroptosis is a type of regulated cell death characterized by iron accumulation and lipid peroxidation. The molecular mechanisms underlying ferroptosis regulation in non-small cell lung cancer (NSCLC) are poorly understood. In this study, we found that protein kinase A (PKA) inhibition enhanced ferroptosis susceptibility in NSCLC cells, as evidenced by reduced cell viability and increased lipid peroxidation. We further identified cAMP-responsive element protein 1 (CREB1), a transcription factor and a substrate of PKA, as a key regulator of ferroptosis. Knockdown of CREB1 sensitized NSCLC cells to ferroptosis inducers (FINs) and abolished the effects of PKA inhibitor and agonist, revealing the pivotal role of CREB1 in ferroptosis regulation. Using a high-throughput screening approach and subsequent validation by chromatin immunoprecipitation (ChIP) and dual-luciferase assays, we discovered that CREB1 transcriptionally activated stearoyl-CoA desaturase (SCD), an enzyme that catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids. SCD conferred ferroptosis resistance by decreasing the availability of polyunsaturated fatty acids for lipid peroxidation, and its overexpression rescued the effect of CREB1 knockdown on ferroptosis in vitro. Besides, CREB1 knockdown suppressed xenograft tumor growth in the presence of Imidazole Ketone Erastin (IKE), a potent FIN, and this effect was reversed by SCD. Finally, we showed that high expression of CREB1 was associated with poor prognosis in NSCLC patients from public datasets and our institution. Collectively, this study illustrates the effect of PKA/CREB1/SCD axis in regulating ferroptosis of NSCLC, targeting this pathway may provide new strategies for treating NSCLC patients.

Background Identified as a hallmark of cancer, the dysregulated cell cycle progression plays an important role in the promotion and progression of lung adenocarcinoma (LUAD). However, the genomic and microenvironment differences between cell cycle progression pathway altered/non-altered LUAD patients remain to be elucidated. Materials and Methods Data of this study were obtained from The Cancer Genome Atlas (TCGA), including simple nucleotide variation, copy number variation (CNV), RNA-seq gene expression, miRNA expression, survival, and clinical information. Besides, 34 LUAD samples from our institution were used as a validation cohort. Differentially expressed genes (DEGs), enrichment analysis, and immune cell infiltration were detected. At last, we built a LASSO-binary Logistic regression model to predict the cell-cycle-related gene mutation (CDKN2A, CCND1, CDK4, CCNE1, and RB1) in LUAD patients and further verified it in the samples from our institution. Results Based on the cell cycle progression pathway status, the LUAD patients were divided into the mutation (n=322) and wild (n=46) groups. Compared to the wild group, the mutation group had a higher mutational load and CNV. Among the 16684 protein-coding genes analyzed, 302 were upregulated, and 354 were downregulated in the mutation group. Enrichment analysis indicated that these DEGs were closely related to metabolism items. After performing immune cell infiltration analysis of 22 immune cells, we found the proportion of 5 immune cells such as monocytes (P<0.01) and dendritic cells (P<0.01) were higher in the wild group. Finally, a cell-cycle-related 15-signature model was built by LASSO-Logistic regression analysis, which could predict the cell cycle progression pathway-related gene mutation (CDKN2A, CCND1, CDK4, CCNE1, and RB1) in LUAD patients. The validation cohorts showed the sensitivity and specificity of this model were 0.667 and 0.929, respectively. Conclusion The genomic and microenvironment characteristics differed between the cell cycle progression pathway altered/non-altered patients with LUAD. Our findings may provide new insight into personalized treatment for LUAD patients.

Background: Ferroptosis is a newly identified regulated cell death characterized by iron-dependent lipid peroxidation and subsequent membrane oxidative damage, which has been implicated in multiple types of cancers. The multi-omics differences between cancer cell lines with high/low ferroptosis scores remain to be elucidated. Methods and Materials: We used RNA-seq gene expression, gene mutation, miRNA expression, metabolites, copy number variation, and drug sensitivity data of cancer cell lines from DEPMAP to detect multi-omics differences associated with ferroptosis. Based on the gene expression data of cancer cell lines, we performed LASSO-Logistic regression analysis to build a ferroptosis-related model. Lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), esophageal cancer (ESCA), bladder cancer (BLCA), cervical cancer (CESC), and head and neck cancer (HNSC) patients from the TCGA database were used as validation cohorts to test the efficacy of this model. Results: After stratifying the cancer cell lines into high score (HS) and low score (LS) groups according to the median of ferroptosis scores generated by gene set variation analysis, we found that IC50 of 66 agents such as oxaliplatin (p < 0.001) were significantly different, among which 65 were higher in the HS group. 851 genes such as KEAP1 and NRAS were differentially muted between the two groups. Differentially expressed genes, miRNAs and metabolites were also detected—multiple items such as IL17F (logFC = 6.58, p < 0.001) differed between the two groups. Unlike the TCGA data generated by bulk RNA-seq, the gene expression data in DEPMAP are from pure cancer cells, so it could better reflect the traits of tumors in cancer patients. Thus, we built a 15-signature model (AUC = 0.878) based on the gene expression data of cancer cell lines. The validation cohorts demonstrated a higher mutational rate of NFE2L2 and higher expression levels of 12 ferroptosis-related genes in HS groups. Conclusion: This article systemically analyzed multi-omics differences between cancer cell lines with high/low ferroptosis scores and a ferroptosis-related model was developed for multiple cancer types. Our findings could improve our understanding of the role of ferroptosis in cancer and provide new insight into treatment for malignant tumors.

Background Lung cancer is the leading cause of cancer-related death worldwide, among which lung adenocarcinoma (LUAD) is the most common type. Identified as a hallmark of cancer, the dysregulated cell cycle progression plays an important role in the promotion and progression of LUAD. This article aims to elucidate the heterogeneity between CDKN2A-CDK/cyclin-RB1 cell cycle progression pathway altered /non-altered patients with LUAD, thus helping us have a better understanding of the effect of the aberrant cell cycle. Material and Methods The data of this study were downloaded from The Cancer Genome Atlas (TCGA) data portal (https://portal.gdc.cancer.gov/) and UCSC Xena Browser (http://xena.ucsc.edu/), including simple nucleotide variation data, RNA-seq gene expression data, survival data, clinical data, and miRNA expression data. After matching the RNA-seq gene expression data, simple nucleotide variation data, miRNA expression data, and survival data with clinical data, 510 gene and long non-coding RNA expression data, 506 simple nucleotide variation data, 440 microRNA expression data, and 497 survival data were included in this study for further analysis. R software (version 4.0.3) was used for analysis. Results After dividing the patients into mutation (n = 57) and wild (n = 453) groups according to the cell cycle progression pathway status, we found no significant difference in survivorship between them. The mutation group had a higher mutational load and mutational rates of various genes such as tumor protein P53 (TP53) compared to the wild group. Subsequently, we analyzed the differentially expressed genes (DEGs) between the two groups. Among the 58387 genes analyzed, 302 were upregulated, and 354 were downregulated in the mutation group. Enrichment analysis indicated that these DEGs were closely related to metabolism items and cell cycle-related events. After performing immune cell infiltration analysis, we found the two groups have different patterns of immune cell profiling. Albeit the immune and stromal scores were higher in the wild group, we failed to find any significant difference between the two groups. Finally, we build a computational model to predict the cell cycle progression pathway-related gene mutation by LASSO-binary logistic regression analysis, the predictive accuracy of which is 0.88. Conclusion In summary, our study compared the genetic and microenvironment differences between cell cycle progression pathway altered /non-altered patients with LUAD by analyzing the data from TCGA datasets. We hope our findings could improve our understanding of the heterogeneity between the two kinds of patients, thus providing new insight into LUAD patients' treatments.

医学机器人精确导航定位的前提是器官的精确分割与识别,本文针对当前深度学习模型在器官分割识别方面需要大量人工标注的不足开展研究,提出了基于视觉显著性检测的医学图像分割模型.该模型首先利用视觉显著性检测算法对医学图像进行显著性检测,然后将检测结果进行正负样本划分,最后将划分结果输入到分类器中对分类器进行训练.该模型克服了学习模型需要大量人工标注数据的问题,简化了模型训练的过程.