Cancer Biomarkers最新文献

{"title":"Mechanism study of serum extracellular nano-vesicles miR-412-3p targeting regulation of TEAD1 in promoting malignant biological behavior of sub-centimeter lung nodules.","authors":"Yuxia Deng,Nishant Patel,Shuang Ding,Haijun Zhang","doi":"10.3233/cbm-240137","DOIUrl":"https://doi.org/10.3233/cbm-240137","url":null,"abstract":"OBJECTIVETo investigate the impact and potential mechanisms of serum extracellular nano-vesicles (sEVs) miR-412-3p released from sub-centimeter lung nodules with a diameter of ⩽ 10 mm on the malignant biological function of micro-nodular lung cancer (mnLC).METHODSA total of 87 participants were included and divided into a mnLC group (n= 30), a benign lung nodule (BLN) group (n= 27), and a healthy people control group (n= 30). Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot (WB) were used to measure the morphological characteristics and surface markers of sEVs. In vitro analysis, real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8 cell proliferation assay, clone formation assay, Transwell, stem cell sphere-forming assay, and WB assay were conducted to verify the effect of miR-412-3p/TEAD1 signaling axis on the biological function of lung cancer cells through, respectively. Further validation was conducted using the serum sEVs of the participants.RESULTSThe expression level of sEVs-miR-412-3p in the mnLC group was significantly higher than that in the BLN and healthy groups (P< 0.01). In lung cancer cell lines, miR-412-3p can negatively regulate the targeted gene TEAD1. The miR-412-3p/TEAD1 signaling axis is involved in promoting the EMT signaling pathway and regulating the malignant biological functions of lung cancer cell proliferation, migration, and stemness (P< 0.05). In addition, sEVs in the mnLC group significantly promoted lung cancer cell proliferation, migration, and stemness compared to the BLN and healthy groups, inhibited the expression of E-cadherin and TEAD1 in lung cancer cells, and promoted the expression of N-cadherin and Vimentin (P< 0.05).CONCLUSIONsEVs-miR-412-3p could promote the biological process of EMT, and lead to the occurrence of malignant biological behavior in sub-centimeter lung nodules. This provides evidence for the miR-412-3p/TEAD1 signaling axis as a potential therapeutic target for mnLC.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.","authors":"Yehia I Mohamed,Sunyoung S Lee,Tarik Demir,Shadi Chamseddine,Zishuo Ian Hu,Lianchun Xiao,Khaled Elsayes,Jeffrey S Morris,Robert A Wolff,Rikita Hiatia,Aliya Qayyum,Asif Rashid,Dan G Duda,James C Yao,Michael LaPelusa,Eugene J Koay,Armeen Mahvash,Ahmed Al Azzam,Ecaterina E Dumbrava,Manal Hassan,Hesham M Amin,Ahmed Omar Kaseb","doi":"10.3233/cbm-230431","DOIUrl":"https://doi.org/10.3233/cbm-230431","url":null,"abstract":"BACKGROUNDCirculating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).OBJECTIVEThis study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.METHODSWe analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.RESULTSOf 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04).CONCLUSIONSctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning identifies a 5-serum cytokine panel for the early detection of chronic atrophy gastritis patients.","authors":"Fangmei An,Yan Ge,Wei Ye,Lin Ji,Ke Chen,Yunfei Wang,Xiaoxue Zhang,Shengrong Dong,Yao Shen,Jiamin Zhao,Xiaojuan Gao,Simon Junankar,Robin Barry Chan,Dimitris Christodoulou,Wen Wen,Peihua Lu,Qiang Zhan","doi":"10.3233/cbm-240023","DOIUrl":"https://doi.org/10.3233/cbm-240023","url":null,"abstract":"BACKGROUNDChronic atrophy gastritis (CAG) is a high-risk pre-cancerous lesion for gastric cancer (GC). The early and accurate detection and discrimination of CAG from benign forms of gastritis (e.g. chronic superficial gastritis, CSG) is critical for optimal management of GC. However, accurate non-invasive methods for the diagnosis of CAG are currently lacking. Cytokines cause inflammation and drive cancer transformation in GC, but their utility as a diagnostic for CAG is poorly characterized.METHODSBlood samples were collected, and 40 cytokines were quantified using a multiplexed immunoassay from 247 patients undergoing screening via endoscopy. Patients were divided into discovery and validation sets. Each cytokine importance was ranked using the feature selection algorithm Boruta. The cytokines with the highest feature importance were selected for machine learning (ML), using the LightGBM algorithm.RESULTSFive serum cytokines (IL-10, TNF-α, Eotaxin, IP-10 and SDF-1a) that could discriminate between CAG and CSG patients were identified and used for predictive model construction. This model was robust and could identify CAG patients with high performance (AUC = 0.88, Accuracy = 0.78). This compared favorably to the conventional approach using the PGI/PGII ratio (AUC = 0.59).CONCLUSIONUsing state-of-the-art ML and a blood-based immunoassay, we developed an improved non-invasive screening method for the detection of precancerous GC lesions.FUNDINGSupported in part by grants from: Jiangsu Science and Technology Project (no. BK20211039); Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2023008); Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021010), Wuxi Science and Technology Bureau Project (no. N20201004); Scientific Research Program of Wuxi Health Commission (Z202208, J202104).","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of RNA-binding protein RBMS3 as a potential biomarker for immunotherapy in bladder cancer.","authors":"Tarimo Fredrick Praygod, Jinlong Li, Hongwei Li, Wanlong Tan, Zhiming Hu, Li Zhou","doi":"10.3233/CBM-230489","DOIUrl":"https://doi.org/10.3233/CBM-230489","url":null,"abstract":"<p><p>RNA-binding protein (RBP) plays pivotal roles in the malignant progression of cancer by regulating gene expression. In this paper, we aimed to develop RBP-based prognostic signature and identify critical hub RBPs in bladder cancer (BLCA). Firstly, a risk model based on differentially expressed RBP gens (DERBPs) between normal and tumor tissues was successfully established, which can predict the tumor stromal score and drug sensitivity. Then two another RBP risk models based on miRNA-correlated RBPs or lncRNA-correlated RBPs were also established, and RBMS3 was identified as the overlapping gene in the three models. Data from multiple bioinformatics databases revealed that RBMS3 was an independent prognostic factor for overall survival (OS), and was associated with an immunosuppressive tumor microenvironment (TME) in BLCA. Further, Single-cell RNA-Seq (scRNA-Seq) data and the human protein altas (HPA) database showed that RBMS3 expression (both mRNA and protein) were up-regulated in BLCA tumor and tumor stromal cells. Finally, RBMS3 was shown to be associated with worse response to BLCA immunotherapy. Overall, RBMS3 is a key prognostic RBP with TME remodeling function and may serve as a target for BLCA immunotherapy.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A computed tomography-based score indicative of lung cancer aggression (SILA) predicts lung adenocarcinomas with low malignant potential or vascular invasion.","authors":"Dylan Steiner, Ju Ae Park, Sarah Singh, Austin Potter, Jonathan Scalera, Jennifer Beane, Kei Suzuki, Marc E Lenburg, Eric J Burks","doi":"10.3233/CBM-230456","DOIUrl":"https://doi.org/10.3233/CBM-230456","url":null,"abstract":"<p><strong>Background: </strong>Histologic grading of lung adenocarcinoma (LUAD) is predictive of outcome but is only possible after surgical resection. A radiomic biomarker predictive of grade has the potential to improve preoperative management of early-stage LUAD.</p><p><strong>Objective: </strong>Validate a prognostic radiomic score indicative of lung cancer aggression (SILA) in surgically resected stage I LUAD (n= 161) histologically graded as indolent low malignant potential (LMP), intermediate, or aggressive vascular invasive (VI) subtypes.</p><p><strong>Methods: </strong>The SILA scores were generated from preoperative CT-scans using the previously validated Computer-Aided Nodule Assessment and Risk Yield (CANARY) software.</p><p><strong>Results: </strong>Cox proportional regression showed significant association between the SILA and 7-year recurrence-free survival (RFS) in a univariate (p< 0.05) and multivariate (p< 0.05) model incorporating age, gender, smoking status, pack years, and extent of resection. The SILA was positively correlated with invasive size (spearman r= 0.54, p= 8.0 × 10 - 14) and negatively correlated with percentage of lepidic histology (spearman r=-0.46, p= 7.1 × 10 - 10). The SILA predicted indolent LMP with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.74 and aggressive VI with an AUC of 0.71, the latter remaining significant when invasive size was included as a covariate in a logistic regression model (p< 0.01).</p><p><strong>Conclusions: </strong>The SILA scoring of preoperative CT scans was prognostic and predictive of resected pathologic grade.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LDCT image biomarkers that matter most for the deep learning classification of indeterminate pulmonary nodules.","authors":"Axel H Masquelin, Nick Cheney, Raúl San José Estépar, Jason H T Bates, C Matthew Kinsey","doi":"10.3233/CBM-230444","DOIUrl":"10.3233/CBM-230444","url":null,"abstract":"<p><strong>Background: </strong>Continued improvement in deep learning methodologies has increased the rate at which deep neural networks are being evaluated for medical applications, including diagnosis of lung cancer. However, there has been limited exploration of the underlying radiological characteristics that the network relies on to identify lung cancer in computed tomography (CT) images.</p><p><strong>Objective: </strong>In this study, we used a combination of image masking and saliency activation maps to systematically explore the contributions of both parenchymal and tumor regions in a CT image to the classification of indeterminate lung nodules.</p><p><strong>Methods: </strong>We selected individuals from the National Lung Screening Trial (NLST) with solid pulmonary nodules 4-20 mm in diameter. Segmentation masks were used to generate three distinct datasets; 1) an Original Dataset containing the complete low-dose CT scans from the NLST, 2) a Parenchyma-Only Dataset in which the tumor regions were covered by a mask, and 3) a Tumor-Only Dataset in which only the tumor regions were included.</p><p><strong>Results: </strong>The Original Dataset significantly outperformed the Parenchyma-Only Dataset and the Tumor-Only Dataset with an AUC of 80.80 ± 3.77% compared to 76.39 ± 3.16% and 78.11 ± 4.32%, respectively. Gradient-weighted class activation mapping (Grad-CAM) of the Original Dataset showed increased attention was being given to the nodule and the tumor-parenchyma boundary when nodules were classified as malignant. This pattern of attention remained unchanged in the case of the Parenchyma-Only Dataset. Nodule size and first-order statistical features of the nodules were significantly different with the average malignant and benign nodule maximum 3d diameter being 23 mm and 12 mm, respectively.</p><p><strong>Conclusion: </strong>We conclude that network performance is linked to textural features of nodules such as kurtosis, entropy and intensity, as well as morphological features such as sphericity and diameter. Furthermore, textural features are more positively associated with malignancy than morphological features.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141289004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary adenocarcinoma of low malignant potential defines indolent NSCLC associated with overdiagnosis in the national lung screening trial.","authors":"Eric J Burks, Travis B Sullivan, Kimberly M Rieger-Christ","doi":"10.3233/CBM-230452","DOIUrl":"https://doi.org/10.3233/CBM-230452","url":null,"abstract":"<p><strong>Background: </strong>The national lung screening trial (NLST) demonstrated a reduction in lung cancer mortality with lowdose CT (LDCT) compared to chest x-ray (CXR) screening. Overdiagnosis was high (79%) among bronchoalveolar carcinoma (BAC) currently replaced by adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and adenocarcinoma of low malignant potential (LMP) exhibiting 100% disease specific survival (DSS).</p><p><strong>Objective: </strong>Compare the outcomes and proportions of BAC, AIS, MIA, and LMP among NLST screendetected stage IA NSCLC with overdiagnosis rate.</p><p><strong>Methods: </strong>Whole slide images were reviewed by a thoracic pathologist from 174 of 409 NLST screen-detected stage IA LUAD. Overdiagnosis rates were calculated from follow-up cancer incidence rates.</p><p><strong>Results: </strong>Most BAC were reclassified as AIS/MIA/LMP (20/35 = 57%). The 7-year DSS was 100% for AIS/MIA/LMP and 94% for BAC. Excluding AIS/MIA/LMP, BAC behaved similarly to NSCLC (7-year DSS: 86% vs. 83%, p= 0.85) The overdiagnosis rate of LDCT stage IA NSCLC was 16.6% at 11.3-years, matching the proportion of AIS/MIA/LMP (16.2%) but not AIS/MIA (3.5%) or BAC (22.8%).</p><p><strong>Conclusions: </strong>AIS/MIA/LMP proportionally matches the overdiagnosis rate among stage IA NSCLC in the NLST, exhibiting 100% 7-year DSS. Biomarkers designed to recognize AIS/MIA/LMP preoperatively, would be useful to prevent overtreatment of indolent screen-detected cancers.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral blood biomarkers associated with combination of immune checkpoint blockade plus chemotherapy in NSCLC.","authors":"Nozomu Kimura, Yoko Tsukita, Risa Ebina-Shibuya, Eisaku Miyauchi, Mitsuhiro Yamada, Daisuke Narita, Ryota Saito, Chihiro Inoue, Naoya Fujino, Tomohiro Ichikawa, Tsutomu Tamada, Hisatoshi Sugiura","doi":"10.3233/CBM-230301","DOIUrl":"https://doi.org/10.3233/CBM-230301","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers predicting clinical outcomes of treating non-small cell lung cancer (NSCLC) with combination of immune checkpoint inhibitors (ICIs) and chemotherapy would be valuable.</p><p><strong>Objective: </strong>This study aims to seek predictors of combination of ICI/chemotherapy response in NSCLC patients using peripheral blood samples.</p><p><strong>Methods: </strong>Patients diagnosed with advanced NSCLC between July 2019 and May 2021 receiving combination of ICI/chemotherapy were included and assessed for partial responses (PR), stable disease (SD) or progressive disease (PD). We measured circulating immune cells, plasma cytokines and chemokines.</p><p><strong>Results: </strong>Nineteen patients were enrolled. The proportions of circulating natural killer (NK) cells within CD45 + cells, programmed death 1 (PD-1) + Tim-3 + T cells within CD4 + cells, and the amount of chemokine C-X-C ligand (CXCL10) in the plasma were significantly elevated in PR relative to SD/PD patients (median 8.1%-vs-2.1%, P= 0.0032; median 1.2%-vs-0.3%, P= 0.0050; and median 122.6 pg/ml-vs-76.0 pg/ml, P= 0.0125, respectively). Patients with 2 or 3 elevated factors had longer progression-free survival than patients with 0 or only one (not reached-vs-5.6 months, P= 0.0002).</p><p><strong>Conclusions: </strong>We conclude that NK cells, CD4 + PD-1 + Tim-3 + T cells, and CXCL10 levels in pre-treatment peripheral blood may predict the efficacy of combination of ICI/chemotherapy in NSCLC.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curating retrospective multimodal and longitudinal data for community cohorts at risk for lung cancer.","authors":"Thomas Z Li, Kaiwen Xu, Neil C Chada, Heidi Chen, Michael Knight, Sanja Antic, Kim L Sandler, Fabien Maldonado, Bennett A Landman, Thomas A Lasko","doi":"10.3233/CBM-230340","DOIUrl":"10.3233/CBM-230340","url":null,"abstract":"<p><strong>Background: </strong>Large community cohorts are useful for lung cancer research, allowing for the analysis of risk factors and development of predictive models.</p><p><strong>Objective: </strong>A robust methodology for (1) identifying lung cancer and pulmonary nodules diagnoses as well as (2) associating multimodal longitudinal data with these events from electronic health record (EHRs) is needed to optimally curate cohorts at scale.</p><p><strong>Methods: </strong>In this study, we leveraged (1) SNOMED concepts to develop ICD-based decision rules for building a cohort that captured lung cancer and pulmonary nodules and (2) clinical knowledge to define time windows for collecting longitudinal imaging and clinical concepts. We curated three cohorts with clinical data and repeated imaging for subjects with pulmonary nodules from our Vanderbilt University Medical Center.</p><p><strong>Results: </strong>Our approach achieved an estimated sensitivity 0.930 (95% CI: [0.879, 0.969]), specificity of 0.996 (95% CI: [0.989, 1.00]), positive predictive value of 0.979 (95% CI: [0.959, 1.000]), and negative predictive value of 0.987 (95% CI: [0.976, 0.994]) for distinguishing lung cancer from subjects with SPNs.</p><p><strong>Conclusion: </strong>This work represents a general strategy for high-throughput curation of multi-modal longitudinal cohorts at risk for lung cancer from routinely collected EHRs.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel disulfidptosis-related prognostic gene signature and experimental validation identify ACTN4 as a novel therapeutic target in lung adenocarcinoma.","authors":"Kai Xie, Bin Wang, Pei Pang, Guangbin Li, Qianqian Yang, Chen Fang, Wei Jiang, Yu Feng, Haitao Ma","doi":"10.3233/CBM-230276","DOIUrl":"https://doi.org/10.3233/CBM-230276","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is a prevalent form of malignancy globally. Disulfidptosis is novel programmed cell death pathway based on disulfide proteins, may have a positive impact on the development of LUAD treatment strategies.</p><p><strong>Objective: </strong>To investigate the impact of disulfidptosis-related genes (DRGs) on the prognosis of LUAD, developed a risk model to facilitate the diagnosis and prognostication of patients. We also explored ACTN4 (DRGs) as a new therapeutic biomarker for LUAD.</p><p><strong>Methods: </strong>We investigated the expression patterns of DRGs in both LUAD and noncancerous tissues. To assess the prognostic value of the DRGs, we developed risk models through univariate Cox analysis and lasso regression. The expression and function of ACTN4 was evaluated by qRT-PCR, immunohistochemistry and in vitro experiments. The TIMER examined the association between ACTN4 expression and immune infiltration in LUAD.</p><p><strong>Results: </strong>Ten differentially expressed DRGs were identified. And ACTN4 was identified as potential risk factors through univariate Cox regression analysis (P< 0.05). ACTN4 expression and riskscore were used to construct a risk model to predict overall survival in LUAD, and high-risk demonstrated a significantly higher mortality rate compared to the low-risk cohort. qRT-PCR and immunohistochemistry assays indicated ACTN4 was upregulated in LUAD, and the upregulation was associated with clinicopathologic features. In vitro experiments showed the knockdown of ACTN4 expression inhibited the proliferation in LUAD cells. The TIMER analysis demonstrated a correlation between the expression of ACTN4 and the infiltration of diverse immune cells. Elevated ACTN4 expression was associated with a reduction in memory B cell count. Additionally, the ACTN4 expression was associated with m6A modification genes.</p><p><strong>Conclusions: </strong>Our study introduced a prognostic model based on DRGs, which could forecast the prognosis of patients with LUAD. The biomarker ACTN4 exhibits promise for the diagnosis and management of LUAD, given its correlation with tumor immune infiltration and m6A modification.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}