Translational cancer research最新文献

{"title":"A novel gene signature based on endoplasmic reticulum stress for predicting prognosis in hepatocellular carcinoma.","authors":"Xuezhi Du, Yingjie He, Penggang Dong, Caigu Yan, Yaqing Wei, Hao Yao, Jinjin Sun","doi":"10.21037/tcr-24-191","DOIUrl":"10.21037/tcr-24-191","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains one of the most common human cancers, the death cases induced by HCC are increasing these years. Endoplasmic reticulum stress (ERS) occurs when misfolded proteins cannot be disposed of properly. It is reported that ERS plays a crucial role in the pathogenesis of human malignant tumors. The aim of this study is to construct a novel gene signature based on ERS for predicting prognosis in HCC.</p><p><strong>Methods: </strong>The data of HCC patients were downloaded from public databases. The Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to construct ERS-related gene signature. The cases were divided into high- and low-risk groups based on the ERS-related gene signature in The Cancer Genome Atlas (TCGA) cohort. Subsequently, the differences in messenger ribonucleic acid (mRNA) expression patterns, immune status, tumor mutation burden (TMB) and copy number variants (CNV) were investigated between high- and low-risk groups. Then, a predictive nomogram according to the ERS-related gene signature and clinicopathological variables was established. At last, we explored the biological functions of <i>TMX1</i> which had the biggest coefficient and we investigated the effect of <i>BRSK2</i> on apoptosis in HCC.</p><p><strong>Results: </strong>In our study, a 9-gene ERS-related gene signature was constructed. The results showed that patients in the low-risk group had a better prognosis than the high-risk group patients. The results of receiver operating characteristic (ROC) curves revealed that the area under the curve (AUC) was 0.784 at 1 year, 0.780 at 2 years, 0.793 at 3 years in the training set. While in validation cohort, this index was 0.694 at 1 year, 0.622 at 2 years, 0.613 at 3 years respectively. The analysis of immune status revealed an immunosuppressive microenvironment in the high-risk group. The analysis of TMB and CNV revealed that the high-risk group patients had a higher genomic mutation frequency. In Univariate Cox regression analysis, the hazard ratio of RiskScore was 2.718 [95% confidence interval (CI): 2.173-3.399]. In Multivariate Cox regression analysis, the hazard ratio of RiskScore was 2.422 (95% CI: 1.805-3.25). Then, we established a nomogram according to the RiskScore and Eastern Cooperative Oncology Group performance status. The AUCs of the nomogram were 0.851 at 1 year, 0.860 at 2 years, and 0.866 at 3 years. At last, we found that <i>TMX1</i> knockdown can inhibit the proliferation and migration of Huh7 and HepG2 cells. In addition, <i>BRSK2</i> knockdown could promote the apoptosis induced by ERS.</p><p><strong>Conclusions: </strong>In our study, a novel ERS-related gene signature was constructed to predict the prognosis of HCC patients. In addition, <i>TMX1</i> and <i>BRSK2</i> could promote the progression of HCC. This study may provide a new understanding for HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 9","pages":"4574-4592"},"PeriodicalIF":1.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475463","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":"Adjuvant treatment in resected biliary cancers: fluoropyrimidines on the spotlight.","authors":"Pedro Luiz Serrano Uson Junior, Mitesh J Borad","doi":"10.21037/tcr-24-1007","DOIUrl":"10.21037/tcr-24-1007","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 9","pages":"4510-4513"},"PeriodicalIF":1.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475524","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":"Disulfidptosis-related gene <i>SLC7A11</i> predicts prognosis and indicates tumor immune infiltration in lung adenocarcinoma.","authors":"Jing Zhu, Hui Ge, Yinsong Chen, She Zhang, Junjie Wu, Weiping Nai, Lingfeng Min","doi":"10.21037/tcr-24-1182","DOIUrl":"10.21037/tcr-24-1182","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is closely associated with factors such as smoking and metabolic disorders. A unique form of cell death known as disulfidptosis, which is regulated by genes like <i>SLC7A11</i>, has emerged as an area of interest; however, its effect on the immune microenvironment in the context of cancer remains largely unexplored. The aim of this study was to analyze the immunoregulatory role of disulfidptosis-related genes in LUAD to unveil and underscore their significance in the process of immune regulation.</p><p><strong>Methods: </strong>This study examined the role of disulfidptosis-related genes in LUAD using data from The Cancer Genome Atlas (TCGA) with a particular focus on immune infiltration and the function of <i>SLC7A11</i>. The research employed a clustering analysis, survival analysis, and immune function assessment, integrating both bulk and single-cell RNA sequencing data, to gain a comprehensive understanding of disulfidptosis in LUAD.</p><p><strong>Results: </strong>The analysis revealed three distinct LUAD clusters, each characterized by different survival rates and patterns of immune cell infiltration. Notably, high expression levels of <i>SLC7A11</i> were associated with a poor prognosis and mechanisms of immune evasion. High SLC7A11 expression is correlated with a poor prognosis and immune evasion in LUAD. These results underscore the significant role of <i>SLC7A11</i> in the progression of disulfidptosis and LUAD.</p><p><strong>Conclusions: </strong>This study sheds new light on the role of disulfidptosis in LUAD, particularly highlighting the immunoregulatory effects of <i>SLC7A11</i>. The findings suggest that targeting <i>SLC7A11</i> could lead to the development of novel therapeutic strategies aimed at enhancing the response to immunotherapy in LUAD patients. To substantiate these results, further experimental validation is needed.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 9","pages":"5064-5072"},"PeriodicalIF":1.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475547","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":"Feasibility and safety of transarterial chemoembolization in patients with liver cancer via the distal radial approach: a single-center retrospective cohort study.","authors":"Xinsen Wang, Lei Xian, Wenlei Zhang, Yang Xu, Delong Zhao, Xue Wang","doi":"10.21037/tcr-24-1231","DOIUrl":"https://doi.org/10.21037/tcr-24-1231","url":null,"abstract":"<p><strong>Background: </strong>The femoral artery is the standard route for transarterial chemoembolization (TACE); however, it is negatively associated with the quality of life of patients, and carries an increased risk of deep vein thrombosis in the lower limbs. We employed the distal radial approach to TACE to assess its feasibility and safety.</p><p><strong>Methods: </strong>We conducted a retrospective study at the First Hospital of Jilin University from August 1, 2020 to October 31, 2023. To be eligible for inclusion in the study, the patients had to meet the following main inclusion criteria: (I) have undergone a preoperative imaging (abdominal computed tomography enhancement or magnetic resonance dynamic enhancement) examination, or have a pathologically confirmed diagnosis of primary liver cancer, and a Child-Pugh score of A or B; and (II) have undergone distal radial artery puncture. The primary endpoint of this study was the success rate of distal radial artery puncture. The secondary endpoints were complications and the duration of the puncture.</p><p><strong>Results: </strong>Among the 343 patients with primary liver cancer (of whom 236 were male and 107 were female), a total of 1,315 distal radial artery punctures were attempted. The success rate was remarkably high at 95.13% (1,251/1,315), with only 64 cases requiring an alternative approach due to failed puncture. The average puncture duration was 20±7.43 minutes. No bleeding and hematoma, no arterial dissection and pseudoaneurysm formation were observed on ultrasound, and the radial pulse was palpable in all patients, highlighting the safety of the procedure. Further, no adverse events of vascular occlusion were observed among the 12 patients who received 6 or more punctures, indicating the sustainability of the distal radial artery access under the premise of adequate vascular protection. The development of this technique requires a learning curve of at least 50 cases to break through the learning baseline and be proficient in distal radial artery blind puncture. This may be the reason why many interventional physicians are reluctant to perform this procedure, adapting to the femoral approach with a shorter learning curve.</p><p><strong>Conclusions: </strong>The distal radial artery approach is feasible and safe in hepatic arterial chemoembolization, and should be widely promoted in TACE.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 8","pages":"4500-4506"},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296261","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 tumor-derived exosomal gene signature predicts prognosis in patients with pancreatic cancer.","authors":"Yang Wang, Chao Liang, Xinbo Liu, Shu-Qun Cheng","doi":"10.21037/tcr-23-2354","DOIUrl":"https://doi.org/10.21037/tcr-23-2354","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a devastating disease with poor prognosis. Accumulating evidence has shown that exosomes and their cargo have the potential to mediate the progression of pancreatic cancer and are promising non-invasive biomarkers for the early detection and prognosis of this malignancy. This study aimed to construct a gene signature from tumor-derived exosomes with high prognostic capacity for pancreatic cancer using bioinformatics analysis.</p><p><strong>Methods: </strong>Gene expression data of solid pancreatic cancer tumors and blood-derived exosome tissues were downloaded from The Cancer Genome Atlas (TCGA) and ExoRBase 2.0. Overlapping differentially expressed genes (DEGs) in the two datasets were analyzed, followed by functional enrichment analysis, protein-protein interaction networks, and weighted gene co-expression network analysis (WGCNA). Using the least absolute shrinkage and selection operator (LASSO) regression of prognosis-related exosomal DEGs, a tumor-derived exosomal gene signature was constructed based on the TCGA dataset, which was validated by an external validation dataset, GSE62452. The prognostic power of this gene signature and its relationship with various pathways and immune cell infiltration were analyzed.</p><p><strong>Results: </strong>A total of 166 overlapping DEGs were identified from the two datasets, which were markedly enriched in functions and pathways associated with the cell cycle. Two key modules and corresponding 70 exosomal DEGs were identified using WGCNA. Using LASSO Cox regression of prognosis-related exosomal DEGs, a tumor-derived exosomal gene signature was built using six exosomal DEGs (<i>ARNTL2</i>, <i>FHL2</i>, <i>KRT19</i>, <i>MMP1</i>, <i>CDCA5</i>, and <i>KIF11</i>), which showed high predictive performance for prognosis in both the training and validation datasets. In addition, this prognostic signature is associated with the differential activation of several pathways, such as the cell cycle, and the infiltration of some immune cells, such as Tregs and CD8+ T cells.</p><p><strong>Conclusions: </strong>This study established a six-exosome gene signature that can accurately predict the prognosis of pancreatic cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 8","pages":"4324-4340"},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296227","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":"Bioinformatics analysis of <i>SH2D4A</i> in glioblastoma multiforme to evaluate immune features and predict prognosis.","authors":"Tian Yang, Chujun Li, Duo Xu, Rui Quan, Lansheng Wang, Yanhong Ren, Zhengkui Zhang, Rutong Yu","doi":"10.21037/tcr-23-2000","DOIUrl":"https://doi.org/10.21037/tcr-23-2000","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer in adults. This study aimed to obtain data on immune cell infiltration based on public datasets and to examine the prognostic significance of SH2 domain containing 4A (<i>SH2D4A</i>) for GBM.</p><p><strong>Methods: </strong><i>SH2D4A</i> expression in GBM was analyzed using a Tumor Immunity Estimation Resource (TIMER) 2.0 dataset, and a gene expression profile interaction analysis (GEPIA), and the results were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The Chinese Glioma Genome Atlas (CGGA) dataset was used to assess the effect of <i>SH2D4A</i> on GBM patient survival. The <i>SH2D4A</i> co-expression network of the LinkedOmics dataset and GeneMANIA dataset was also investigated. Least absolute shrinkage and selection operator (LASSO) regression models and a nomogram were constructed to assess the prognosis of GBM patients. A Gene Set Enrichment Analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset to find functional differences. The relationship between <i>SH2D4A</i> expression and tumor-infiltrating immune cells was analyzed using xCELL, the Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, and the TIMER dataset.</p><p><strong>Results: </strong>We discovered that <i>SH2D4A</i> expression was upregulated in GBM patients, and elevated SH2D4A expression was also substantially correlated with tumor grade. The survival curve analysis and multivariate Cox regression analysis showed that high <i>SH2D4A</i> expression was a significant independent predictor of poor overall survival (OS) in GBM patients. The immunoassay results suggested that altered <i>SH2D4A</i> expression may affect the immune infiltration of GBM tissues and thus the survival outcomes of GBM patients.</p><p><strong>Conclusions: </strong>In addition to being a possible prognostic marker and therapeutic target for GBM, <i>SH2D4A</i> may also accelerate the progression of GBM.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 8","pages":"4242-4256"},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296232","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":"Exploring the therapeutic potential of simvastatin in pancreatic neuroendocrine neoplasms: insights into cell cycle regulation and apoptosis.","authors":"Xiao-Ting Shi, Li-Jun Yan, Fei-Yu Lu, Mu-Jie Ye, Ping Yu, Yuan Zhong, Jin-Hao Chen, Chun-Hua Hu, Qi-Yun Tang","doi":"10.21037/tcr-24-363","DOIUrl":"https://doi.org/10.21037/tcr-24-363","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic neuroendocrine neoplasm (pNEN) poses significant challenges in clinical management due to their heterogeneity and limited treatment options. In this study, we investigated the potential of simvastatin (SIM) as an anti-tumor agent in pNEN.</p><p><strong>Methods: </strong>We conducted cell culture experiments using QGP-1 and BON-1 cell lines and assessed cell viability, proliferation, migration, and invasion following SIM treatment. To further validate our findings, we performed <i>in vivo</i> experiments using a mouse xenograft model. Additionally, we investigated the underlying molecular mechanisms by analyzing changes in cell cycle progression, apoptosis, and signaling pathways.</p><p><strong>Results: </strong>SIM treatment suppresses pNEN growth both <i>in vitro</i> and <i>in vivo</i>, and led to G1 phase arrest in QGP-1 cells. In contrast, SIM affected both the G1-S and G2-M phase transitions in the BON-1 cell line and induced apoptosis, indicating diverse mechanisms of action. Furthermore, SIM treatment resulted in decreased expression of mutant p53 (mutp53) in BON-1 cells, suggesting a potential therapeutic strategy targeting mutp53. Modulation of the MAPK pathway was also implicated in QGP-1 cells.</p><p><strong>Conclusions: </strong>Our study highlights SIM as a promising candidate for pNEN treatment by inducing cell cycle arrest or apoptosis, potentially through the p53 and MAPK pathways. Further research is warranted to fully elucidate SIM's mechanisms of action and evaluate its therapeutic potential in clinical settings.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 8","pages":"4315-4323"},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296260","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":"The potential role of breast MRI in evaluation of triple-negative breast cancer and fibroadenoma of less than 3 cm.","authors":"Zifan Wei, Xue Chen, Yiwen Yang, Ling Yang, Xinxing Ma","doi":"10.21037/tcr-24-498","DOIUrl":"https://doi.org/10.21037/tcr-24-498","url":null,"abstract":"<p><strong>Background: </strong>The majority of small-sized (<3 cm) triple-negative breast cancer (TNBC) exhibit smooth margins upon palpation and are often oval or rounded masses. Distinguishing these masses preoperatively from fibroadenomas (FAs) would be very meaningful for clinical practice. The aim of our study was to evaluate the magnetic resonance imaging (MRI) appearance of TNBC and differentiate it from FAs.</p><p><strong>Methods: </strong>In this retrospective single-center study, we included 37 patients with TNBCs and 36 patients with FAs who underwent breast MRI. We employed the χ² test and <i>t-</i>test to compare the differences in morphological features, dynamic contrast-enhanced MRI (DCE-MRI) parameters, and apparent diffusion coefficient (ADC) values between the two groups. Additionally, we constructed non-parametric receiver operating characteristic (ROC) curves using ADC values, with pathological results serving as the gold standard.</p><p><strong>Results: </strong>A total of 37 TNBC lesions and 39 FA lesions were included in the final analysis. TNBCs exhibited more frequent irregular shape, irregular margins, peritumoral edema, fast enhancement in the initial phase, rim enhancement, and time-signal intensity curve (TIC) type III compared to FAs (all P<0.05). Conversely, low-signal segregation in T2-weighted imaging (T2WI) and TIC type I were commonly found in FAs. The mean ADC value of TNBCs was significantly lower than that of FAs [(1.104±0.13)×10^-3 <i>vs</i>. (1.613±0.16)×10^-3 mm²/s, P<0.05]. The cutoff ADC for differentiating TNBCs from FAs was 1.239×10^-3 mm²/s, yielding an area under the curve (AUC) of 0.997, a sensitivity of 94.6%, and a specificity of 100%.</p><p><strong>Conclusions: </strong>The morphological presentation of MRI, internal enhancement features of the mass, TIC curves, and ADC values provide valuable differential diagnostic information for TNBC and FA masses with a maximum diameter of less than 3 cm.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 8","pages":"4042-4051"},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296278","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":"Bioinformatic prediction of miR-320a as a potential negative regulator of CDGSH iron-sulfur domain 2 (<i>CISD2</i>), involved in lung adenocarcinoma bone metastasis via MYC activation, and associated with tumor immune infiltration.","authors":"Xiaoxi Zhao, Lei Li, Yancheng Li, Yanxiao Liu, Hua Wang, Nika Samadzadeh Tabrizi, Zhou Ye, Ziru Zhao","doi":"10.21037/tcr-24-1188","DOIUrl":"https://doi.org/10.21037/tcr-24-1188","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ferroptosis, a form of regulated cell death associated with iron-dependent lipid peroxidation, plays a role in cancer progression. However, the specific mechanisms of ferroptosis in lung adenocarcinoma (LUAD) bone metastasis (BM) remain unclear. Using bioinformatics analysis, this study sought to identify the ferroptosis-associated genes involved in BM in LUAD, thus providing potential novel targets for the treatment of BM in LUAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The RNA expression dataset GSE10799 was acquired from the Gene Expression Omnibus (GEO) database, and intersected with the ferroptosis dataset to identify ferroptosis-related differentially expressed genes (DEGs). The expression of candidate genes and their correlation with the prognosis of LUAD patients were validated in The Cancer Genome Atlas (TCGA) database. A protein gene interaction network was constructed using GeneMania and Retrieval of Interacting Genes/Proteins (STRING) databases. The association between the candidate genes and immune cells was assessed via TCGA and Tumor IMmune Estimation Resource (TIMER) databases. The potential mechanisms were elucidated by a gene set enrichment analysis (GSEA). The relevant microRNAs (miRNAs or miRs) that bind to the 3'untranslated region (3'UTR) end of candidate genes' mRNA was explored using the TargetScan database. The expression of these candidate miRNAs in LUAD was validated and the correlation between candidate miRNAs and candidate mRNAs was tested using the TCGA database. Finally, the clinical data of 40 LUAD patients were retrospectively analyzed to evaluate the clinical value of candidate gene expression for LUAD BM patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In this research, 15 ferroptosis-related DEGs in LUAD BM were identified. TCGA database analysis indicated that patients with low levels of CDGSH iron-sulfur domain 2 (&lt;i&gt;CISD2&lt;/i&gt;) in LUAD had better disease-specific survival (DSS), overall survival (OS), and a better progression-free interval (PFI) than those with high levels of &lt;i&gt;CISD2&lt;/i&gt;. The TIMER database results show that the expression of &lt;i&gt;CISD2&lt;/i&gt; is correlated with the infiltration levels of various immune cells. The GSEA indicated that &lt;i&gt;CISD2&lt;/i&gt; might influence biological activity in LUAD by participating in cell-cycle regulation, mitochondrial translation, DNA damage repair, c-&lt;i&gt;Myc&lt;/i&gt; (&lt;i&gt;MYC&lt;/i&gt;) activation, and the P53 signaling pathway. Through the combined analysis of the TargetScan and TCGA databases, hsa-miR-320a was identified as the optimal upstream regulatory miRNA. The immunohistochemistry data indicated that the positive CISD2 expression rates and immunohistochemistry scores of the patients with BM were significantly higher than those of the patients without BM (P&lt;0.05). The high expression of CISD2 is a significant risk factor for BM in LUAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The downregulation of &lt;i&gt;CISD2&lt;/i&gt; expression may extend DSS, OS, and the PFI of LUAD ","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 8","pages":"4485-4499"},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296231","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":"Identifying epithelial-mesenchymal transition-related genes as prognostic biomarkers and therapeutic targets of hepatocellular carcinoma by integrated analysis of single-cell and bulk-RNA sequencing data.","authors":"Chen Chen, Shunyi Wang, Yuhong Tang, Huanxiang Liu, Daoyuan Tu, Bingbing Su, Rui Peng, Shengjie Jin, Guoqing Jiang, Jun Cao, Chi Zhang, Dousheng Bai","doi":"10.21037/tcr-24-521","DOIUrl":"https://doi.org/10.21037/tcr-24-521","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally. Patients with advanced HCC tend to have poor prognoses and shortened survival. Recently, data from bulk RNA sequencing have been employed to discover prognostic markers for various cancers. However, they fall short in precisely identifying core molecular and cellular activities within tumor cells. In our present study, we combined bulk-RNA sequencing (bulk RNA-seq) data with single-cell RNA sequencing (scRNA-seq) to develop a prognostic model for HCC. The goal of our research is to uncover new biomarkers and enhance the accuracy of HCC prognosis prediction.</p><p><strong>Methods: </strong>Integrating single-cell sequencing data with transcriptomics were used to identify epithelial-mesenchymal transition (EMT)-related genes (ERGs) implicated in HCC progression and their clinical significance was elucidated. Utilizing marker genes derived from core cells and ERGs, we constructed a prognostic model using univariate Cox analysis, exploring a multitude of algorithmic combinations, and further refining it through multivariate Cox analysis. Additionally, we conducted an in-depth investigation into the disparities in clinicopathological features, immune microenvironment composition, immune checkpoint expression, and chemotherapeutic drug sensitivity profiles between high- and low-risk patient cohorts.</p><p><strong>Results: </strong>We developed a prognostic model predicated on the expression profiles of eight signature genes, namely <i>HSP90AA1</i>, <i>CIRBP</i>, <i>CCR7</i>, <i>S100A9</i>, <i>ADAM17</i>, <i>ENG</i>, <i>PGF</i>, and <i>INPP4B</i>, aiming at predicting overall survival (OS) outcomes. Notably, patients classified with high-risk scores exhibited a propensity towards diminished OS rates, heightened frequencies of stage III-IV disease, increased tumor mutational burden (TMB), augmented immune cell infiltration, and diminished responsiveness to immunotherapeutic interventions.</p><p><strong>Conclusions: </strong>This study presented a novel prognostic model for predicting the survival of HCC patients by integrating scRNA-seq and bulk RNA-seq data. The risk score emerges as a promising independent prognostic factor, showing a correlation with the immune microenvironment and clinicopathological features. It provided new clinical tools for predicting prognosis and aided future research into the pathogenesis of HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 8","pages":"4257-4277"},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296266","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}