Translational Oncology最新文献

{"title":"The 7-Methylguanosine (m7G) methylation METTL1 acts as a potential biomarker of clear cell renal cell carcinoma progression","authors":"Yi Liu ,&nbsp;Yanji Zhan ,&nbsp;Jiao Liu ,&nbsp;Zhengze Shen ,&nbsp;Yudong Hu ,&nbsp;Ling Zhong ,&nbsp;Yuan Yu ,&nbsp;Bin Tang ,&nbsp;Jing Guo","doi":"10.1016/j.tranon.2024.102202","DOIUrl":"10.1016/j.tranon.2024.102202","url":null,"abstract":"<div><div><strong>Background:</strong> Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. 7-Methylguanosine (m7G), one of the most prevalent RNA modifications, has been reported to play an important role in ccRCC progression; however, the specific regulators of m7G modification that are involved in this function remain unclear. This study aimed to explore the correlation between regulators of m7G methylation and ccRCC progression using unsupervised machine learning methods.</div><div><strong>Methods:</strong> Transcriptome and clinical data of ccRCC were retrieved from The Cancer Genome Atlas (TCGA) database to identify differentially expressed m7G-related genes associated with the overall survival of patients with ccRCC. To construct and validate a prognostic risk model, TCGA dataset samples were divided into training and test sets. A multiple-gene risk signature was constructed using least absolute shrinkage and selection operator Cox regression analysis, and its prognostic significance was assessed using Cox regression and survival analyses. Finally, immunohistochemistry was performed to verify the prognostic significance of this signature.</div><div><strong>Results:</strong> In total, 537 patients with ccRCC were included in this study. We found that 26 m7G RNA methylation regulators that were significantly differentially expressed. Univariate and multifactorial Cox regression analyses revealed that METTL1 expression was associated with ccRCC progression.</div><div><strong>Conclusions:</strong> METTL1 associated with m7G may serve as a potential biomarker for ccRCC prognosis and diagnosis. Moreover, it may affect the prognosis of ccRCC by regulating the tumor immune microenvironment, providing a potential therapeutic target for immunotherapy. These results provide a new perspective on the role of M7G-related RNAs in ccRCC pathogenesis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102202"},"PeriodicalIF":5.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical efficacies of different neoadjuvant therapies for non-small cell lung cancer","authors":"Xin-chen Tan ,&nbsp;Xin-yun Song ,&nbsp;Meng-qi Jiang ,&nbsp;Neng-yang Wang ,&nbsp;Jun Liu ,&nbsp;Wen Yu ,&nbsp;Qin Zhang ,&nbsp;Xu-wei Cai ,&nbsp;Wen Feng ,&nbsp;Xiao-long Fu","doi":"10.1016/j.tranon.2024.102195","DOIUrl":"10.1016/j.tranon.2024.102195","url":null,"abstract":"<div><div>Neoadjuvant therapy followed by surgery is a common clinical strategy for operable non-small cell lung cancer (NSCLC), and the mainstream neoadjuvant therapies include chemoimmunotherapy, targeted therapy, and chemotherapy. However, there is a lack of studies to report the difference in benefits between these treatment modalities in the same institution. Therefore, this study aimed to depict the short-term efficacy of radiology and pathology achieved by different therapies and their impact on long-term survival as well as the underlying clinical significance. A total of 243 NSCLC patients who underwent different neoadjuvant therapies were eligible for inclusion. Demographic, radiological, and pathological features of patients were recorded. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. The objective response rates (ORR) of primary tumor in the chemoimmunotherapy, targeted therapy, and chemotherapy cohorts were 48.95 %, 57.58 %, and 34.09 % respectively, major pathological response (MPR) rates were 58.74 %, 15.15 %, and 20.83 % (<em>P</em>&lt;.0001), and pathological complete response (pCR) rates were 41.26 %, 0 %, and 11.11 % (<em>P</em>&lt;.0001). For consistency between imaging and pathological evaluation, Cohen's Kappa were 0.275, 0.233, and 0.330. The EFS of MPR group was significantly longer than that of non-MPR group in the chemoimmunotherapy and chemotherapy cohorts (<em>P</em>=.0077**&amp;.0343*, HR=0.3287&amp;0.3715), but this improvement was not observed in the targeted therapy cohort. Neoadjuvant chemoimmunotherapy often underestimates pathological efficacy in imaging but shows consistent long-term outcomes. Neoadjuvant chemotherapy with moderate overall effectiveness has a significant correlation between short-term benefits and reduced recurrence. Neoadjuvant targeted therapy shows remarkable short-term imaging improvements but often fails to convert into sustained long-term survival.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102195"},"PeriodicalIF":5.0,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omics demonstrates enhanced antitumor efficacy of donafenib combined with FADS2 inhibition in hepatocellular carcinoma","authors":"Hui Li,&nbsp;Yafeng Dai,&nbsp;Di Wu,&nbsp;Song Gao,&nbsp;Jianhai Guo,&nbsp;Pengjun Zhang,&nbsp;Hui Chen,&nbsp;Fuxin Kou,&nbsp;Shaoxing Liu,&nbsp;Aiwei Feng,&nbsp;Baojiang Liu,&nbsp;Dongdong Hou,&nbsp;Xu Zhu","doi":"10.1016/j.tranon.2024.102142","DOIUrl":"10.1016/j.tranon.2024.102142","url":null,"abstract":"<div><div>Pharmacotherapy is crucial for advanced hepatocellular carcinoma (HCC). The multi-kinase inhibitor donafenib offers superior survival benefits over sorafenib. Donafenib has first-line status, but there is limited research for combination therapies with this anticancer agent. This study aimed to delineate donafenib's antitumor effects, including transcriptomics and proteomics to characterize gene expression changes in donafenib-treated HCC cell lines. In vitro and in vivo tumorigenicity studies were conducted to evaluate the combined antitumor effects of donafenib. Proteomic and transcriptomic analyses identified that donafenib downregulated fatty acid desaturase 2 <em>(FADS2</em>) at the protein and mRNA levels. In vitro and in vivo assays revealed an inhibitory effect of <em>FADS2</em> blockade on HCC cell malignancy. The combination of donafenib and the <em>FADS2</em> inhibitor sc-26,196 produced synergistic antitumor action, enhancing therapeutic efficacy in HCC cell lines and xenografted tumors in nude mice. These findings highlight the potential of <em>FADS2</em> as a biomarker for HCC and show a promising combinatorial therapy for its treatment. Thus, we provide a theoretical basis for translating laboratory research into clinical applications.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102142"},"PeriodicalIF":5.0,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRas plays a negative role in regulating IDO1 expression","authors":"Xiandong Peng,&nbsp;Eunji Lee,&nbsp;Jialu liang,&nbsp;Tania Colon,&nbsp;Franklin Tran,&nbsp;Byeong H. Choi,&nbsp;Wei Dai","doi":"10.1016/j.tranon.2024.102167","DOIUrl":"10.1016/j.tranon.2024.102167","url":null,"abstract":"<div><div>Ras proteins are integral to the mediation of signaling cascades to downstream effectors, regulating a multitude of cellular processes. Mutations within Ras and its associated signaling pathways are implicated in various human pathologies, including inflammatory disorders and malignancies. The immune checkpoint proteins, programmed cell death protein 1 (PD-1) and its ligands PD-L1, along with Indoleamine 2,3-dioxygenase-1 (IDO1), are pivotal in facilitating tumor immune escape. While the influence of oncogenic Ras on PD-L1 expression is extensively documented, the regulatory role of KRas in IDO1 expression remains inadequately understood. In the current study, we demonstrate that IDO1 and PD-L1 expressions are differentially regulated in KRas-mutant cancers. Treatment with the KRas^G12C-specific inhibitor, ARS-1620, significantly increased IDO1 expression, which inversely correlated with PD-L1 expression in the KRas^G12C-mutant H358 cell line. Notably, IDO1 expression was slightly diminished in KRas-mutant patients with lung and pancreatic ductal adenocarcinomas. Experimental data revealed that IFN-γ induces IDO1 expression; however, this induction is attenuated in the presence of constitutively active KRas. These findings suggest that KRas signaling negatively regulates IDO1 expression while enhancing PD-L1 expression. Moreover, the induction of IDO1 expression following KRas inhibition appears to operate independently of the MAPK pathway. Our results propose that concurrent targeting of KRas and IDO1 could potentiate therapeutic efficacy in KRas-mutant cancers, overcoming resistance to immune checkpoint blockade.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102167"},"PeriodicalIF":5.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of bioenergetics enhances the radio-sensitivity of patient-derived glioblastoma tumorspheres","authors":"Seo Jin Kim ,&nbsp;Junseong Park ,&nbsp;Jin-kyoung Shim ,&nbsp;Ran Joo Choi ,&nbsp;Ju Hyung Moon ,&nbsp;Eui Hyun Kim ,&nbsp;Wan-Yee Teo ,&nbsp;Jong Hee Chang ,&nbsp;Seok-Gu Kang","doi":"10.1016/j.tranon.2024.102197","DOIUrl":"10.1016/j.tranon.2024.102197","url":null,"abstract":"<div><h3>Background</h3><div>Despite available treatment approaches, including surgical resection along with chemotherapy and radiotherapy, glioblastoma (GBM), the most prevalent primary brain tumor, remains associated with a grim prognosis. Although radiotherapy is central to GBM treatment, its combination with bioenergetics regulators has not been validated in clinical practice. Here, we hypothesized that bioenergetics regulators can enhance the radio-sensitivity of GBM tumorspheres (TSs).</div></div><div><h3>Methods</h3><div>Gene expression profiles of GBM patient-derived TSs were obtained through microarray and RNA-seq. In vitro treatment efficacy was assessed using clonogenic assay, 3D invasion assay, neurosphere formation assay, and flow cytometry. Protein expression was measured via western blot, and γH2AX foci were detected via immunofluorescence. In vivo efficacy was confirmed in an orthotopic xenograft model.</div></div><div><h3>Results</h3><div>Based on radiation response-associated gene expression, GBM TSs were classified into high- or low-radioresistant groups. Among the five bioenergetics regulators, the pentose phosphate pathway inhibitor DHEA and the glycolysis inhibitor 2-DG notably enhanced the efficacy of ionizing radiation (IR) efficacy in vitro, reducing the survival fraction, stemness, and invasiveness in high- and low-radioresistant TSs. Combination with 2-DG further stimulated IR-induced DNA damage response and apoptosis in low-radioresistant GBM TSs. RNA-seq analysis revealed a downregulation of bioenergetics- and cell cycle-associated genes, whereas extracellular matrix- and cell adhesion-associated genes were enhanced by combined IR and 2-DG treatment. This therapeutic regimen extended survival and diminished tumor size in mouse xenograft models.</div></div><div><h3>Conclusions</h3><div>Our data suggest that combination with bioenergetics regulator 2-DG enhances the radio-sensitivity of GBM TSs, highlighting the clinical potential of this combined regimen.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102197"},"PeriodicalIF":5.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative transcriptomic analysis uncovers molecular heterogeneity in hepatobiliary cancers","authors":"Nabanita Roy ,&nbsp;Ria Lodh ,&nbsp;Susmita Mandal ,&nbsp;Mohit Kumar Jolly ,&nbsp;Anupam Sarma ,&nbsp;Dhruba Kumar Bhattacharyya ,&nbsp;Pankaj Barah","doi":"10.1016/j.tranon.2024.102192","DOIUrl":"10.1016/j.tranon.2024.102192","url":null,"abstract":"<div><div>Hepatobiliary cancers (HBCs) pose a major global health challenge, with a lack of effective targeted biomarkers. Due to their complex anatomical locations, shared risk factors, and the limitations of targeted therapies, generalized treatment strategies are often used for gallbladder cancer (GBC), hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (ICC). This study aimed to identify specific transcriptomic signatures in GBC, HCC, and ICC. The transcriptomic data analysis revealed distinct expression profiles, highlighting complex molecular heterogeneity within these cancers, even within the same organ system. Functional annotation revealed distinct biological pathways associated with each type of HBCs. GBC was linked to cell cycle regulation, HCC was associated with immune system modulation, and ICC was involved in metabolic dysregulation, particularly lipid metabolism. Gene co-expression network (GCN) and protein-protein interaction (PPI) network analyses identified potential key genes, such as <em>MAPK3</em> and <em>ERBB2</em> in GBC, <em>AC069287.1</em> and <em>ACTN2</em> in HCC, and <em>TRPC1</em> and <em>BACE1</em> in ICC. The FOX family of transcription factors (TFs) was conserved across all three cancer types. To further explore the relationship between Epithelial-Mesenchymal Transition (EMT) and the identified hub genes and TFs, an EMT score analysis was conducted. This analysis revealed distinct phenotypic characteristics in each cancer type, with TFs identified in GBC and ICC showing a stronger correlation with EMT compared to those in HCC. External validation using <em>The Cancer Genome Atlas</em> (TCGA) databases confirmed the expression of candidate genes, underscoring their potential as therapeutic targets. These findings provide valuable insights into the molecular heterogeneity and complexity of HBCs, opening new avenues for personalized therapeutic interventions.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102192"},"PeriodicalIF":5.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization","authors":"Siyuan Wu ,&nbsp;Gaochao Wang ,&nbsp;Likai Gu ,&nbsp;Yinjie Zhang ,&nbsp;Zhihuai Wang","doi":"10.1016/j.tranon.2024.102189","DOIUrl":"10.1016/j.tranon.2024.102189","url":null,"abstract":"<div><div>The study highlights that RPS21, a gene encoding a component of the 40S ribosomal subunit, plays an oncogenic role in hepatocellular carcinoma (HCC) and may influence tumor aggressiveness by affecting antioxidant capacity. RPS21 was found to be upregulated in HCC through RNA-sequencing of clinical samples and analysis of the TCGA database. Kaplan-Meier survival analyses linked higher RPS21 expression to lower survival rates across multiple metrics (OS, PFS, RFS, DSS). Mutation analysis via the cBioPortal showed that primarily amplifications in RPS21 are associated with a poorer prognosis. Tissue microarrays confirmed higher RPS21 levels in tumor samples, which were associated with more advanced clinical stages and grades. Experimental interventions involving lentiviral knockdown or overexpression of RPS21 significantly altered HCC cell proliferation and migration. These findings were supported by mouse models, which showed impacts on tumor growth and metastasis. Further mechanistic studies indicated that RPS21 modulates the ubiquitination and stability of GPX4, a key player in ferroptosis and oxidative stress regulation in HCC cells. This comprehensive study, which merges bioinformatic analysis with laboratory research, positions RPS21 as a viable target for HCC therapy and opens new pathways for understanding and treating liver cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102189"},"PeriodicalIF":5.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells","authors":"Lin Xin ,&nbsp;Jiang Liu ,&nbsp;Jun-Yan Lai ,&nbsp;He-Song Xu ,&nbsp;Luo-Jun Fan ,&nbsp;Yong-Hui Zou ,&nbsp;Qi Zhou ,&nbsp;Zhen- Qi Yue ,&nbsp;Jin-Heng Gan","doi":"10.1016/j.tranon.2024.102181","DOIUrl":"10.1016/j.tranon.2024.102181","url":null,"abstract":"<div><h3>Background</h3><div>The limited curative effect of PD-L1/PD-1 blockades presents challenges to immunotherapy for advanced gastric cancer. We have found that methionine restriction (MR) enhances the drug resistance of gastric carcinoma cells. We aimed to explore whether MR can enhance the efficacy of PD-L1/PD-1 blockades in gastric cancer.</div></div><div><h3>Methods</h3><div>To conduct MR, gastric carcinoma cells were transfected with LV-METase in vitro, and 615 mice were injected with MFC cells with stable METase expression in vivo. Flow cytometry was conducted to measure the proportions of M1/M2 macrophages and CD8⁺ GZMB⁺/IFN-γ⁺ T cells. Additionally, the levels of M1/M2 macrophage markers and MIF were also detected.</div></div><div><h3>Results</h3><div>MR increased M1 and down-regulated M2 macrophages. MR suppressed MIF levels in gastric carcinoma cells, while the addition of anti-MIF neutralizing antibody inhibited the effect of MR on macrophage M1/M2 polarization. MR enhanced the increase of the proportion of CD8⁺ GZMB⁺ T cells and CD8⁺ IFN-γ⁺ T cells induced by PD-L1/PD-1 blockades. In vivo detection verified the efficacy of the combination of MR and PD-L1/PD-1 blockades on gastric cancer.</div></div><div><h3>Conclusions</h3><div>MR inhibits the secretion of MIF by gastric carcinoma cells, promotes macrophage M1 polarization, and enhances the therapeutic effect of PD-L1/PD-1 blockades in gastric cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102181"},"PeriodicalIF":5.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining methylated RNF180 and SFRP2 plasma biomarkers for noninvasive diagnosis of gastric cancer","authors":"Zhihao Dai ,&nbsp;Jin Jiang ,&nbsp;Qianping Chen ,&nbsp;Minghua Bai ,&nbsp;Quanquan Sun ,&nbsp;Yanru Feng ,&nbsp;Dong Liu ,&nbsp;Dong Wang ,&nbsp;Tong Zhang ,&nbsp;Liang Han ,&nbsp;Litheng Ng ,&nbsp;Jun Zheng ,&nbsp;Hao Zou ,&nbsp;Wei Mao ,&nbsp;Ji Zhu","doi":"10.1016/j.tranon.2024.102190","DOIUrl":"10.1016/j.tranon.2024.102190","url":null,"abstract":"<div><h3>Introduction</h3><div>Gastric cancer (GC) is a common malignant tumor, and early diagnosis significantly improves patient survival rates. This study aimed to investigate the diagnostic value of ring finger protein 180 (<em>RNF180</em>) and secreted frizzled protein 2 (<em>SFRP2</em>) in GC.</div></div><div><h3>Materials &amp; Methods</h3><div>A total of 165 healthy individuals, 34 patients with precancerous gastric lesions, and 104 patients with confirmed GC were divided into training and validation sets; methylated <em>RNF180</em> and <em>SFRP2</em> were detected in circulating DNA from blood samples. Six models, including those based on logistic regression, Naive Bayes, K-nearest neighbor algorithm, glmnet, neural network, and random forest (RF) were built and validated. Area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value were determined.</div></div><div><h3>Results</h3><div>In the training set, the RF model with <em>RNF180</em> and <em>SFRP2</em> (R + S) had an AUC of 0.839 (95 % CI: 0.727–0.951), sensitivity of 60.3 %, and specificity of 85.5 % for diagnosing GC. The RF model with R + S+ Tumor markers had an AUC of 0.849 (95 % CI: 0.717–0.981), sensitivity of 62.8 %, and specificity of 87.1 %. In the validation set, the RF model with R + S had an AUC of 0.844 (95 % CI: 0.774–0.923), sensitivity of 87.8 %, and specificity of 69.2 %. The RF model with R + S + Tumor markers had an AUC of 0.858 (95 % CI: 0.781–0.939), sensitivity of 85.4 %, and specificity of 76.9 %.</div></div><div><h3>Conclusion</h3><div>Our results suggest that <em>RNF180</em> and <em>SFRP2</em> could serve as diagnostic biomarkers for GC when using the RF model.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102190"},"PeriodicalIF":5.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer","authors":"Bo Gao ,&nbsp;Xinyi Gou ,&nbsp;Caizhen Feng ,&nbsp;Yinli Zhang ,&nbsp;Huining Gu ,&nbsp;Fan Chai ,&nbsp;Yi Wang ,&nbsp;Yingjiang Ye ,&nbsp;Nan Hong ,&nbsp;Guohua Hu ,&nbsp;Boshi Sun ,&nbsp;Jin Cheng ,&nbsp;Hao Yang","doi":"10.1016/j.tranon.2024.102188","DOIUrl":"10.1016/j.tranon.2024.102188","url":null,"abstract":"<div><div>Extramural venous invasion (EMVI) detected by computed tomography has been identified as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). Cancer-associated fibroblasts (CAFs) are critical for remodeling the tumor microenvironment in GCs. Here, we report that MFAP5+ CAFs promote the formation of EMVI imaging in GC. We detected gene expression in pathological samples from 13 advanced GC patients with EMVI. Radiogenomics results showed the degree of CAFs infiltration was directly proportional to the EMVI score and EMT pathway in GC patients. Single-cell sequencing data analysis results showed that MFAP5+CAFs subtypes in GC were negatively correlated with patient prognosis and were enriched in tumor lactylation modification and EMT pathways. Immunohistochemistry results showed that the expression of MFAP5, L-lactyl and EMT markers in GC tissues was proportional to the EMVI score. CAF from gastric cancer tissue was extracted using collagenase method and co-cultured with GC cell line in vitro. After lentivirus knockdown of MFAP5 in CAFs, the levels of L-lactoyl and histone lactylation modifications were significantly reduced, and the sphere-forming and vascularization abilities of CAFs were significantly inhibited. Cell function experiments showed that MFAP5+ CAFs can affect the EMT, metastasis and invasion capabilities of GC cells. In vivo experimental results of the nude mouse in situ EMVI model suggest that MFAP5+ CAF may promote the formation of EMVI imaging features in GC by regulating lactylation modification. This innovative work may provide important new references for the diagnosis and treatment of GC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102188"},"PeriodicalIF":5.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}