Cancer research最新文献

{"title":"SEMA3G-NRP1 Signaling Functions as an Immune Checkpoint that Enables Tumor Immune Evasion by Impairing T Cell Cytotoxicity","authors":"Hao Chi, Shouyan Deng, Ke Xu, Yibo Zhang, Teng Song, Jianghong Yu, Yiting Wang, Jiayang Liu, Yuan Zhang, Jiawei Shi, Yungang Wang, Jie Xu","doi":"10.1158/0008-5472.can-24-2223","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-2223","url":null,"abstract":"T cells within the tumor microenvironment frequently exhibit dysfunctional characteristics that compromise their ability to elicit both innate and therapeutic-induced immune responses. Regulators of immune dysfunction represent therapeutic targets to activate anti-tumor immunity. In this study, we identified semaphorin 3G (SEMA3G) as a key regulator of immune responses in cancer. SEMA3G was widely upregulated in diverse human cancers, and its expression was positively correlated with tumor progression. SEMA3G acted as a ligand that inhibited the activation and functionality of T cells. A comprehensive receptor screening approach demonstrated that SEMA3G exhibited a significantly stronger affinity for neuropilin NRP1 compared to NRP2. Furthermore, SEMA3G primarily impeded T-cell functions via NRP1. Disruption of SEMA3G using CRISPR/Cas9 technology or blockade with a neutralizing antibody effectively restored the cytotoxicity of CD8+ T cells and inhibited the growth of tumors in vivo. This research underscores the role of SEMA3G in T-cell dysfunction within tumors and proposes a targeting SEMA3G as a cancer immunotherapeutic strategy.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"37 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBV Remodels PP2A Complexes to Rewire Kinase Signaling in Hepatocellular Carcinoma","authors":"Rigney E. Turnham, Adriana Pitea, Gwendolyn M. Jang, Zhong Xu, Huat Chye Lim, Alex L. Choi, John Von Dollen, Rebecca S. Levin, James T. Webber, Elizabeth McCarthy, Junjie Hu, Xiaolei Li, Li Che, Ananya Singh, Alex Yoon, Gary Chan, Robin K. Kelley, Danielle L. Swaney, Wei Zhang, Sourav Bandyopadhyay, Fabian J. Theis, Manon Eckhardt, Xin Chen, Kevan M. Shokat, Trey Ideker, Nevan J. Krogan, John D. Gordan","doi":"10.1158/0008-5472.can-24-0456","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-0456","url":null,"abstract":"Hepatitis B virus (HBV) infections promote liver cancer initiation by inducing inflammation and cellular stress. Despite the primarily indirect effect on oncogenesis, HBV is associated with a recurrent genomic phenotype in HCC, suggesting that it impacts the biology of established HCC. Characterization of the interaction of HBV with host proteins and the mechanistic contributions of HBV to HCC initiation and maintenance could provide insights into HCC biology and uncover therapeutic vulnerabilities. Here, we used affinity purification mass spectrometry to comprehensively map a network of 145 physical interactions between HBV and human proteins in hepatocellular carcinoma (HCC). A subset of the host factors targeted by HBV proteins were preferentially mutated in non-HBV-associated HCC, suggesting that their interaction with HBV influences HCC biology. HBV interacted with proteins involved in mRNA splicing, mitogenic signaling, and DNA repair, with the latter set interacting with the HBV oncoprotein X (HBx). HBx remodeled the PP2A phosphatase complex by excluding striatin regulatory subunits from the PP2A holoenzyme, and the HBx effects on PP2A caused Hippo kinase activation. In parallel, HBx activated mTOR complex 2 (mTORC2), which can prevent YAP degradation. mTORC2-mediated upregulation of YAP was observed in human HCC specimens and mouse HCC models and could be targeted with mTOR kinase inhibitors. Thus, HBV interaction with host proteins rewires HCC signaling rather than directly activating mitogenic pathways, provide an alternative paradigm for the cellular effects of a tumor promoting virus.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"9 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gain-of-Function Chromatin Remodeling Activity of Oncogenic FOXL2-C134W Reprograms Glucocorticoid Receptor Occupancy to Drive Granulosa Cell Tumors","authors":"Thomas Welte, Veena K. Vuttaradhi, Eleonora Y. Khlebus, Allison Brodsky, Alejandra Flores Legarreta, Joseph Celestino, Reid T. Powell, Clifford C. Stephan, Nghi Nguyen, Jian Li, Shiro Takamatsu, Katherine Calzoncinth, Anil K. Sood, David M. Gershenson, P. Andrew Futreal, Barrett Lawson, Robert Tyler. Hillman","doi":"10.1158/0008-5472.can-24-2341","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-2341","url":null,"abstract":"Adult type ovarian granulosa cell tumors (AGCTs) are rare malignancies with the near universal c.C402G (p.Cys134Trp) somatic mutation in FOXL2, a Forkhead box-family transcription factor important for ovarian function. Relapsed AGCT is incurable, but the mechanism of the unique FOXL2 mutation could confer therapeutic vulnerabilities. To identify FOXL2-C134W-dependent pharmacologic synergies, we created and characterized endogenous FOXL2 isogenic AGCT cells and an AGCT tumoroid biobank. A drug screen identified that glucocorticoids promote FOXL2-C134W-dependent AGCT growth. Epigenetic investigation revealed that the Cys134Trp mutation exposes latent DNA sequence-specific chromatin remodeling activity in FOXL2. FOXL2-C134W-dependent chromatin remodeling activity redirected glucocorticoid receptor chromatin occupancy to drive hyaluronan synthase 2 gene expression and increase extracellular hyaluronan secretion. Treatment of AGCT models with hyaluronidase reduced viability, and dexamethasone rescued this effect. Combinatorial drug-drug interaction experiments demonstrated that dexamethasone antagonizes the potency of paclitaxel, a chemotherapy agent frequently used in the treatment of AGCT. Thus, gain-of-function pioneering activity contributes to the oncogenic mechanism of FOXL2-C134W and creates a potentially targetable synergy with glucocorticoid signaling.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"20 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Arachidonic Acid Metabolism Enhances Immunotherapy Efficacy in ARID1A-Deficient Colorectal Cancer","authors":"Luying Cui, Ruiqi Liu, Shuling Han, Chunhui Zhang, Bojun Wang, Yuli Ruan, Xuefan Yu, Yien Li, Yuanfei Yao, Xin Guan, Yuanyu Liao, Dan Su, Yue Ma, Shuijie Li, Chao Liu, Yanqiao Zhang","doi":"10.1158/0008-5472.can-24-1611","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-1611","url":null,"abstract":"ARID1A, a core constituent of SWI/SNF complex, is mutated in approximately 10% of colorectal cancers (CRC). While ARID1A deficiency corresponds to heightened immune activity in CRC, immune checkpoint inhibitors (ICIs) have shown limited efficacy in these tumors. The discovery of targetable vulnerabilities associated with ARID1A deficiency in CRC could expand treatment options for patients. In this study, we demonstrated that arachidonic acid metabolism inhibitors synergize with ICIs in ARID1A-deficient CRC by enhancing the activity of CD8+ T cells and inhibiting vasculogenic mimicry (VM). Epigenetic analysis using ATAC-seq and ChIP-qPCR revealed that the lack of ARID1A results in reduced levels of PTGS1 and PTGS2, the key enzymes that control the arachidonic acid pathway. Low PTGS1 and PTGS2 expression generated a reliance on the remaining functionality of the arachidonic acid pathway in ARID1A-deficient cells. The arachidonic acid pathway inhibitor aspirin selectively inhibited the growth of ARID1A-deficient CRC, and aspirin sensitized tumors lacking ARID1A to immunotherapy. Together, these findings suggest that blocking arachidonic acid metabolism can enhance immune responses against tumors by activating CD8+ T cells and inhibiting VM, which synergizes with ICIs to improve treatment of ARID1A-deficient CRC.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"212 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHC-Hammer decodes HLA disruption in tumors","authors":"Timothy Sears, Hannah Carter","doi":"10.1158/0008-5472.can-24-4553","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-4553","url":null,"abstract":"Tumors utilize various mechanisms of HLA disruption in order to evade immune surveillance. Previous computational tools have interrogated specific aspects of this process, yet a holistic picture of HLA loss of heterozygosity (LOH), transcriptomic suppression, and alternative splicing has remained challenging. In a recent Nature Genetics study, Puttick and colleagues introduced MHC Hammer, a robust computational toolkit designed to dissect the complexities of HLA disruptions that mediate immune evasion in cancer. By analyzing comprehensive genomic and transcriptomic data across several large cancer cohorts, the study highlights the prevalence of HLA disruptions–particularly alternative splicing events–across various tumor types and identifies HLA LOH as an important immune evasion mechanism during metastasis in lung adenocarcinoma.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"12 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"spatialGE is a User-Friendly Web Application that Facilitates Spatial Transcriptomics Data Analysis","authors":"Oscar E. Ospina, Roberto Manjarres-Betancur, Guillermo Gonzalez-Calderon, Alex C. Soupir, Inna Smalley, Kenneth Y. Tsai, Joseph Markowitz, Ethan Vallebuona, Anders E. Berglund, Steven A. Eschrich, Xiaoqing Yu, Brooke L. Fridley","doi":"10.1158/0008-5472.can-24-2346","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-2346","url":null,"abstract":"Spatial transcriptomics (ST) is a powerful tool for understanding tissue biology and disease mechanisms. However, the advanced data analysis and programming skills required can hinder researchers from realizing of the full potential of ST. To address this, we developed spatialGE, a web application that simplifies the analysis of ST data. The application spatialGE provided a user-friendly interface that guides users without programming expertise through various analysis pipelines, including quality control, normalization, domain detection, phenotyping, and multiple spatial analyses. It also enabled comparative analysis among samples and supported various ST technologies. The utility of spatialGE was demonstrated through its application in studying the tumor microenvironment of two data sets: 10X Visium samples from a cohort of melanoma metastasis and Nanostring CosMx fields of vision from a cohort of Merkel cell carcinoma samples. These results support the ability of spatialGE to identify spatial gene expression patterns that provide valuable insights into the tumor microenvironment and highlight its utility in democratizing ST data analysis for the wider scientific community.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"abs/2206.03626 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma","authors":"Catriona A. Ford, Dana Koludrovic, Patricia P. Centeno, Mona Foth, Elpida Tsonou, Nikola Vlahov, Nathalie Sphyris, Kathryn Gilroy, Courtney Bull, Colin Nixon, Bryan Serrels, Alison F. Munro, John C. Dawson, Neil O. Carragher, Valeria Pavet, David C. Hornigold, Philip D. Dunne, Julian Downward, Heidi C. Welch, Simon T. Barry, Owen J. Sansom, Andrew D. Campbell","doi":"10.1158/0008-5472.can-23-2814","DOIUrl":"https://doi.org/10.1158/0008-5472.can-23-2814","url":null,"abstract":"Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, which are associated with resistance to BRAF-targeting therapies. Targeting the RAC1-GTPase pathway, including the upstream activator PREX2 and the downstream effector PI3Kβ, could be a potential strategy for overcoming therapeutic resistance, limiting melanoma recurrence, and suppressing metastatic progression. Here, we used genetically engineered mouse models and patient-derived BRAFV600E-driven melanoma cell lines to dissect the role of PREX2 in melanomagenesis and response to therapy. While PREX2 was dispensable for the initiation and progression of melanoma, its loss conferred sensitivity to clinically relevant therapeutics targeting the MAPK pathway. Importantly, genetic and pharmacological targeting of PI3Kβ phenocopied PREX2 deficiency, sensitizing model systems to therapy. These data reveal a druggable PREX2/RAC1/PI3Kβ signaling axis in BRAF-mutant melanoma that could be exploited clinically.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"79 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energy Stress-induced CircEPB41(2) Promotes Lipogenesis in Hepatocellular Carcinoma","authors":"Yang Yang, Jingjing Luo, Zhongyu Wang, Kaiyue Liu, Keyi Feng, Fang Wang, Yide Mei","doi":"10.1158/0008-5472.can-24-1630","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-1630","url":null,"abstract":"The tumor microenvironment plays a pivotal role in the metabolic reprogramming of cancer cells. A better understanding of the underlying mechanisms regulating cancer metabolism could help identify potential therapeutic targets. Here, we identified circEPB41(2) as a metabolically regulated circular RNA that mediates lipid metabolism in hepatocellular carcinoma (HCC). CircEPB41(2) was induced in response to glucose deprivation via HNRNPA1-dependent alternative splicing. Upregulation of circEPB41(2) led to enhanced lipogenic gene expression that promoted lipogenesis. Mechanistically, circEPB41(2) cooperated with the m6A demethylase FTO to decrease the mRNA stability of the histone deacetylase SIRT6, thereby increasing H3K9ac and H3K27ac levels to activate lipogenic gene expression. Silencing of circEPB41(2) inhibited both in vitro proliferation of HCC cells and in vivo growth of tumor xenografts. Clinically, circEPB41(2) was elevated in HCC, and high circEPB41(2) expression was associated with poor patient prognosis. Overall, this study reveals that circEPB41(2) is an important regulator of lipid metabolic reprogramming and indicates that targeting the circEPB41(2)-FTO-SIRT6 axis could represent a promising anti-cancer strategy for treating HCC.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"133 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LTβR Agonism Promotes Antitumor Immune Responses via Modulation of the Tumor Microenvironment.","authors":"Disi An, Guoying Chen, Wei-Yi Cheng, Katja Mohrs, Christina Adler, Namita T Gupta, Gurinder S Atwal, David J DiLillo, Christopher Daly, John C Lin, Frank Kuhnert","doi":"10.1158/0008-5472.CAN-23-2716","DOIUrl":"10.1158/0008-5472.CAN-23-2716","url":null,"abstract":"<p><p>The presence of high endothelial venules (HEV) and tertiary lymphoid structures (TLS) in solid tumors is correlated with favorable prognosis and better responses to immune checkpoint blockade in many cancer types. Elucidation of the molecular mechanisms underlying intratumoral HEV and TLS formation and their contribution to antitumor responses may facilitate the development of improved treatment strategies. Lymphotoxin β receptor (LTβR) signaling is a critical regulator of lymph node organogenesis and can cooperate with antiangiogenic and immune checkpoint blockade treatment to augment tumor-associated HEV formation. In this study, we demonstrated that LTβR signaling modulates the tumor microenvironment via multiple mechanisms to promote antitumor T-cell responses. Systemic activation of the LTβR pathway via agonistic antibody treatment induced tumor-specific HEV formation, upregulated the expression of TLS-related chemokines, and enhanced dendritic cell (DC) and T-cell infiltration and activation in syngeneic tumor models. In vitro studies confirmed direct effects of LTβR agonism on DC activation and maturation and associated DC-mediated T-cell activation. Single-agent LTβR agonist treatment inhibited syngeneic tumor growth in a CD8+ T-cell-dependent and HEV-dependent manner, and the LTβR agonist enhanced antitumor effects of anti-PD-1 and CAR T-cell therapies. An in vivo tumor screen for TLS-inducing cytokines revealed that the combination of LTβR agonism and lymphotoxin ⍺ expression promoted robust intratumoral TLS induction and enhanced tumor responses to anti-CTLA4 treatment. Collectively, this study highlights crucial functions of LTβR signaling in modulating the tumor microenvironment and could inform future HEV/TLS-based strategies for cancer treatments. Significance: LTβR mediates tumor-specific  high endothelial venule formation and immunomodulation of the tumor microenvironment that promotes antitumor immune responses, supporting LTβR agonism as an approach to enhance the antitumor efficacy of immunotherapies.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":" ","pages":"3984-4001"},"PeriodicalIF":12.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NUAK1-Mediated Phosphorylation of NADK Mitigates ROS Accumulation to Promote Osimertinib Resistance in Non-Small Cell Lung Carcinoma.","authors":"Wei Lin, Na Wang, Shihao Wu, Mingxin Diao, Quanfu Huang, Kuo Li, Peiyuan Mei, Xiaojun Wang, Yongde Liao, Yunchong Meng","doi":"10.1158/0008-5472.CAN-24-0249","DOIUrl":"10.1158/0008-5472.CAN-24-0249","url":null,"abstract":"<p><p>Osimertinib, a third generation epidermal growth factor receptor tyrosine kinase inhibitor, is approved as a first-line therapy in patients with advanced non-small cell lung carcinoma (NSCLC) with EGFR-activating mutations or the T790M resistance mutation. However, the efficacy of osimertinib is limited due to acquired resistance, highlighting the need to elucidate resistance mechanisms to facilitate the development of improved treatment strategies. Here, we screened for significantly upregulated genes encoding protein kinases in osimertinib-resistant NSCLC cells and identified NUAK1 as a pivotal regulator of osimertinib resistance. NUAK1 was highly expressed in osimertinib-resistant NSCLC and promoted the emergence of osimertinib resistance. Genetic or pharmacological blockade of NUAK1 restored the sensitivity of resistant NSCLC cells to osimertinib in vitro and in vivo. Mechanistically, NUAK1 directly interacted with and phosphorylated nicotinamide adenine dinucleotide kinase (NADK) at serine 64 (S64), which mitigated osimertinib-induced accumulation of reactive oxygen species (ROS) and contributed to the acquisition of osimertinib resistance in NSCLC. Furthermore, virtual drug screening identified T21195 as an inhibitor of NADK-S64 phosphorylation, and T21195 synergized with osimertinib to reverse acquired resistance by inducing ROS accumulation. Collectively, these findings highlight the role of the NUAK1-NADK axis in governing osimertinib resistance in NSCLC and indicate the potential of targeting this axis as a strategy for circumventing resistance. Significance: Phosphorylation of NADK by NUAK1 diminishes ROS accumulation and confers resistance to osimertinib, identifying NUAK1-NADK signaling as a potential therapeutic target for improving the response to EGFR inhibition in lung cancer.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":" ","pages":"4081-4098"},"PeriodicalIF":12.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}