{"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":"206 1","pages":""},"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}
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
{"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":"23 1","pages":""},"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":"40 1","pages":""},"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}
Dylan Steiner, Ju Ae Park, Sarah Singh, Austin Potter, Jonathan Scalera, Jennifer Beane, Kei Suzuki, Marc E Lenburg, Eric J Burks
{"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":"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 (<math><mrow><mi>n</mi><mo>=</mo><mi></mi></mrow></math> 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 (<math><mrow><mi>p</mi><mo><</mo><mi></mi></mrow></math> 0.05) and multivariate (<math><mrow><mi>p</mi><mo><</mo><mi></mi></mrow></math> 0.05) model incorporating age, gender, smoking status, pack years, and extent of resection. The SILA was positively correlated with invasive size (spearman <math><mrow><mi>r</mi><mo>=</mo><mi></mi></mrow></math> 0.54, <math><mrow><mi>p</mi><mo>=</mo><mi></mi></mrow></math> 8.0 <math><mo>×</mo></math> 10 <sup>- 14</sup>) and negatively correlated with percentage of lepidic histology (spearman <math><mrow><mi>r</mi><mo>=</mo><mo>-</mo></mrow></math>0.46, <math><mrow><mi>p</mi><mo>=</mo><mi></mi></mrow></math> 7.1 <math><mo>×</mo></math> 10 <sup>- 10</sup>). 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 (<math><mrow><mi>p</mi><mo><</mo><mi></mi></mrow></math> 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":" ","pages":"CBM230456"},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226792/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhixiang Zhang, Jipeng Guo, Chongwen Gong, Sai Wu, Yanlei Sun
{"title":"KIAA1429-mediated RXFP1 attenuates non-small cell lung cancer tumorigenesis via N6-methyladenosine modification.","authors":"Zhixiang Zhang, Jipeng Guo, Chongwen Gong, Sai Wu, Yanlei Sun","doi":"10.3233/CBM-230188","DOIUrl":"10.3233/CBM-230188","url":null,"abstract":"<p><strong>Background: </strong>N6-methyladenosine (m<sup>6</sup>A) modification has been associated with non-small cell lung cancer (NSCLC) tumorigenesis.</p><p><strong>Objectives: </strong>This study aimed to determine the functions of Vir-like m<sup>6</sup>A methyltransferase-associated (KIAA1429) and relaxin family peptide receptor 1 (RXFP1) in NSCLC.</p><p><strong>Methods: </strong>A quantitative real-time polymerase chain reaction was used to analyze the mRNA levels of KIAA1429 and RXFP1 in NSCLC. After silencing KIAA1429 or RXFP1 in NSCLC cells, changes in the malignant phenotypes of NSCLC cells were assessed using cell counting kit-8, colony formation, and transwell assays. Finally, the m<sup>6</sup>A modification of RXFP1 mediated by KIAA1429 was confirmed using luciferase, methylated RNA immunoprecipitation, and western blot assays.</p><p><strong>Results: </strong>KIAA1429 and RXFP1 were upregulated and downregulated in NSCLC, respectively. Silencing of KIAA1429 attenuated the viability, migration, and invasion of NSCLC cells, whereas silencing of RXFP1 showed the opposite function in NSCLC cells. Moreover, RXFP1 expression was inhibited by KIAA1429 via m<sup>6</sup>A-modification. Therefore, silencing RXFP1 reversed the inhibitory effect of KIAA1429 knockdown in NSCLC cells.</p><p><strong>Conclusion: </strong>Our findings confirmed that the KIAA1429/RXFP1 axis promotes NSCLC tumorigenesis. This is the first study to reveal the inhibitory function of RXFP1 in NSCLC via KIAA1429-mediated m<sup>6</sup>A-modification. These findings may help identify new biomarkers for targeted NSCLC therapy.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"CBM230188"},"PeriodicalIF":2.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013816","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":"Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma.","authors":"Gehan Hammad, Samah Mamdouh, Dina Mohamed Seoudi, Mohamed Ismail Seleem, Gehan Safwat, Rania Hassan Mohamed","doi":"10.3233/CBM-230134","DOIUrl":"10.3233/CBM-230134","url":null,"abstract":"<p><strong>Background: </strong>P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features.</p><p><strong>Methods: </strong>The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis.</p><p><strong>Results: </strong>Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p< 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant.</p><p><strong>Conclusion: </strong>PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"95-111"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11002723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479472","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}
Zhengtai Li, Hongjiang Li, Kun Fang, Xinglei Lin, Changyuan Yu
{"title":"Uncovering the link between human endogenous retroviruses, inflammatory pathways, and gastric cancer development.","authors":"Zhengtai Li, Hongjiang Li, Kun Fang, Xinglei Lin, Changyuan Yu","doi":"10.3233/CBM-230417","DOIUrl":"10.3233/CBM-230417","url":null,"abstract":"<p><strong>Background: </strong>Endogenous retroviruses, previously deemed \"junk\" DNA, have gained attention in recent scientific studies. These inherited genomic elements are now recognized for their potential roles in diseases, especially cancer, highlighting their value as potential diagnostic or therapeutic targets.</p><p><strong>Objective: </strong>This research aims to explore the association between human endogenous retroviruses (HERV) and gastric cancer, focusing on discerning HERV expression patterns and understanding their implications in gastric cancer pathology.</p><p><strong>Methods: </strong>A quantitative analysis of HERV expression was conducted, employing Support Vector Machine (SVM) and AdaBoost algorithms to identify discriminative HERVs. The co-regulation network between protein-coding genes and HERVs was constructed using the Weighted Gene Co-expression Network Analysis (WGCNA).</p><p><strong>Results: </strong>Three distinct HERVs (LTR16A|72|451, LTR91|636|874, LTR27D|87|222) were identified as significantly different. Strong correlations were found between HERVs, and gene sets enriched in the inflammatory pathway.</p><p><strong>Conclusions: </strong>HERVs appear to influence abnormal inflammatory responses, suggesting a pivotal role in gastric cancer development.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"103-113"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333437","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":"Long non-coding RNAs PTENP1, GNG12-AS1, MAGI2-AS3 and MEG3 as tumor suppressors in breast cancer and their associations with clinicopathological parameters.","authors":"Luděk Záveský, Eva Jandáková, Vít Weinberger, Luboš Minář, Milada Kohoutová, Ondřej Slanař","doi":"10.3233/CBM-230259","DOIUrl":"10.3233/CBM-230259","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease.</p><p><strong>Objective: </strong>Evaluation of novel long non-coding RNAs biomarkers for breast cancer.</p><p><strong>Methods: </strong>The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics.</p><p><strong>Results: </strong>The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality.</p><p><strong>Conclusions: </strong>The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"61-78"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567654","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}
Zhi Yi Zhao, Yin Cao, Hong Liang Wang, Ling Yun Liu
{"title":"A risk model based on lncRNA-miRNA-mRNA gene signature for predicting prognosis of patients with bladder cancer.","authors":"Zhi Yi Zhao, Yin Cao, Hong Liang Wang, Ling Yun Liu","doi":"10.3233/CBM-230216","DOIUrl":"10.3233/CBM-230216","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to analyze lncRNAs, miRNAs, and mRNA expression profiles of bladder cancer (BC) patients, thereby establishing a gene signature-based risk model for predicting prognosis of patients with BC.</p><p><strong>Methods: </strong>We downloaded the expression data of lncRNAs, miRNAs and mRNA from The Cancer Genome Atlas (TCGA) as training cohort including 19 healthy control samples and 401 BC samples. The differentially expressed RNAs (DERs) were screened using limma package, and the competing endogenous RNAs (ceRNA) regulatory network was constructed and visualized by the cytoscape. Candidate DERs were screened to construct the risk score model and nomogram for predicting the overall survival (OS) time and prognosis of BC patients. The prognostic value was verified using a validation cohort in GSE13507.</p><p><strong>Results: </strong>Based on 13 selected. lncRNAs, miRNAs and mRNA screened using L1-penalized algorithm, BC patients were classified into two groups: high-risk group (including 201 patients ) and low risk group (including 200 patients). The high-risk group's OS time ( hazard ratio [HR], 2.160; 95% CI, 1.586 to 2.942; P= 5.678e-07) was poorer than that of low-risk groups' (HR, 1.675; 95% CI, 1.037 to 2.713; P= 3.393 e-02) in the training cohort. The area under curve (AUC) for training and validation datasets were 0.852. Younger patients (age ⩽ 60 years) had an improved OS than the patients with advanced age (age > 60 years) (HR 1.033, 95% CI 1.017 to 1.049; p= 2.544E-05). We built a predictive model based on the TCGA cohort by using nomograms, including clinicopathological factors such as age, recurrence rate, and prognostic score.</p><p><strong>Conclusions: </strong>The risk model based on 13 DERs patterns could well predict the prognosis for patients with BC.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"277-287"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673684","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}
Wenceng Pei, Minren Jiang, Haiyan Liu, Jiahong Song, Jian Hu
{"title":"The prognostic and antitumor roles of key genes of ferroptosis in liver hepatocellular cancer and stomach adenocarcinoma.","authors":"Wenceng Pei, Minren Jiang, Haiyan Liu, Jiahong Song, Jian Hu","doi":"10.3233/CBM-230114","DOIUrl":"10.3233/CBM-230114","url":null,"abstract":"<p><strong>Background: </strong>Liver hepatocellular cancer (LIHC) and stomach adenocarcinoma (STAD) are common malignancies with high lethal ratios worldwide. Great progress has been achieved by using diverse therapeutic strategies; however, these diseases still have an unfavourable prognosis. Ferroptosis inducer drugs, unlike apoptosis-related drugs, can overcome the resistance to cancer therapy caused by traditional chemicals. However, the relationship between overall survival (OS) and ferroptosis-related genes, as well as the mechanisms involved, are largely unclear.</p><p><strong>Methods: </strong>The expression levels of AIFM2, GPX4, ACSL4, FTH1, NOS1, and PTGS2 in LIHC and STAD were obtained from UALCAN. The correlations of OS with these gene expression levels were obtained using the Kaplan-Meier Plotter database. The OS associated with genetic mutations of those genes compared to that of unchanged genes was analysed using the TIMER website. GO and KEGG enrichment analyses of ferroptosis-related genes and their coexpressed genes in LIHC and STAD were conducted using the STRING and DAVID databases. The relationship of PTGS2 and ACSL4 to immune cell infiltration was analysed using the TIMER website. The viability and GPX5 expression levels in LIHC cells treated with RSL3 and As2O3 were detected by MTT methods and western blotting, respectively.</p><p><strong>Results: </strong>Our results showed that GPX4, FTH1 and AIFM2 were overexpressed in LIHC and STAD. High levels of GPX4, FTH1 and AIFM2 were prominently correlated with better prognosis in LIHC. However, GPX and FTH1 in STAD did not show significant correlations with OS. AIFM2 in STAD had the opposite trend with OS compared with that in LIHC. Moreover, a high mutation rate of these genes (35.74%) was also observed in LIHC patients, and genetic mutation of these genes was correlated with shorter OS. In contrast, the genetic mutation of these genes did not change OS in STAD. Enrichment analysis showed that the respiratory electron transport chain, cell chemotaxis and T-cell migration were related to ferroptosis. ASCL4 and PTGS2 coexpressed with cytokines associated with immune cell infiltration. Compared to RSL3 or As2O3 alone, As2O3 plus RSL3 significantly inhibited the growth of Huh7 cells. GPX4 was downregulated to an undetectable level when in combination with RSL3.</p><p><strong>Conclusions: </strong>Our results indicated that ferroptosis-related genes might play an important role in LIHC and STAD and might be risk factors for overall survival in LIHC and STAD.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"335-347"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139941349","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}