Translational cancer research最新文献

{"title":"Pan-cancer bioinformatics analysis of hepatic leukemia factor and further validation in colorectal cancer.","authors":"Yirong Lin, Zuming Xiong, Yongjun Yang, Wenxin Li, Wei Huang, Minglin Lin, Sen Zhang","doi":"10.21037/tcr-23-2274","DOIUrl":"10.21037/tcr-23-2274","url":null,"abstract":"<p><strong>Background: </strong>Hepatic leukemia factor (HLF) is associated with cancer onset, growth, and progression; however, little is known regarding its biological role in pan-cancer. In order to further evaluate the diagnostic and prognostic value of HLF in pan-cancer and colorectal cancer (CRC), we performed comprehensive bioinformatics analyses of the molecular mechanism of HLF in pan-cancer, with subsequent verification in CRC.</p><p><strong>Methods: </strong>We downloaded data (gene expression, clinical data, follow-up duration, and immune-related data) related to 33 solid tumor types from UCSC Xena (University of California Santa Cruz cancer database, https://xena.ucsc.edu/). HLF expression was analyzed in pan-cancer, and its diagnostic efficacy, prognostic value, and correlation with pathological stage and cancer immunity were determined. We also analyzed gene alterations in HLF and biological processes involved in its regulation in pan-cancer. Using CRC data in The Cancer Genome Atlas (TCGA), we assessed correlations between HLF and CRC diagnosis, prognosis, and drug sensitivity and performed functional enrichment analyses. Moreover, we constructed an HLF-related ceRNA regulatory network. Finally, we externally validated HLF expression and diagnostic and prognostic value in CRC using Gene Expression Omnibus (GEO) database, as well as by performing <i>in vitro</i> experiments.</p><p><strong>Results: </strong>HLF expression was downregulated in most tumors, and HLF showed good predictive potential for pan-cancer diagnosis and prognosis. It was closely related to the clinicopathological stages of pan-cancer. Further, HLF was associated with tumor microenvironment and immune cell infiltration in many tumors. Analyses involving cBioPortal revealed changes in HLF amplifications and mutations in most tumors. HLF was also closely associated with microsatellite instability and tumor mutational burden in pan-cancer and involved in regulating various tumor-related pathways and biological processes. In CRC, HLF expression was similarly downregulated, with implications for CRC diagnosis and prognosis. Functional enrichment analysis indicated the association of HLF with many cancer-related pathways. Further, HLF was associated with drug (e.g., oxaliplatin) sensitivity in CRC. The ceRNA regulatory network showed multigene regulation of HLF in CRC. External validation involving GEO databases and quantitative real-time polymerase chain reaction (qRT-PCR) data substantiated these findings.</p><p><strong>Conclusions: </strong>HLF expression generally exhibited downregulation in pan-cancer, contributing to tumor occurrence and development by regulating various biological processes and affecting tumor immune characteristics. HLF was also closely related to CRC occurrence and development. We believe HLF can serve as a reliable diagnostic, prognostic, and immune biomarker for pan-cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983330","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":"Prognostic factors and treatment strategies of limited-stage primary esophageal small-cell carcinoma-a SEER database analysis.","authors":"Yang Yang, Haizhou Guo, Qianping Li, Weipeng Huang","doi":"10.21037/tcr-24-311","DOIUrl":"10.21037/tcr-24-311","url":null,"abstract":"<p><strong>Background: </strong>Primary esophageal small-cell carcinoma (PESC) is a rare tumor with poor efficacy, and there is currently no standardized treatment method. Our aim is to explore the prognostic factors and possible optimal treatment modalities for limited-stage PESC.</p><p><strong>Methods: </strong>We retrospectively searched the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019 for data of patients with limited-stage PESC. Kaplan-Meier method was used to plot survival curves, calculate survival rates, and Log-rank was used to test the differences among survival curves. Prognostic factors were explored through univariate and multivariate Cox regression survival analyses; Cox regression survival analysis was also conducted to analyze the risk of death among treatment groups and compare the survival differences among each treatment group. The non-single treatment (ST) group was defined as the comprehensive treatment (CT) group and it was compared against the ST group.</p><p><strong>Results: </strong>A total of 186 cases of limited-stage PESC were included in the study, there were differences in survival time among different groups due to differences in age, year, median household income, and N stage (P<0.001, P=0.041, P=0.002, P=0.001). The median overall survival (mOS) of the surgical group (19 months) was longer than that of the nonsurgical group (11 months) (P=0.01). The mOS of the chemotherapy group (16 months) was longer than that of the non-chemotherapy group (4 months) (P<0.001). The mOS of the radiotherapy group (16 months) was longer than that of the non-radiotherapy group (8 months) (P<0.001). Univariate analysis showed that age ≥80 years (P=0.006), year (1997-2007) (P=0.01), year (2008-2019) (P=0.01), N2 (P=0.003), surgery (P=0.02), radiotherapy (P<0.001), and chemotherapy (P<0.001) were prognostic factors affecting overall survival (OS) in limited-stage PESC patients. Multivariate analysis showed that SEER stage (P=0.02), age (P=0.007), radiotherapy (P<0.001), surgery (P=0.006), and chemotherapy (P<0.001) were independent prognostic factors affecting OS in patients of limited-stage PESC. Prognosis was better in the non-monotherapy group than in each monotherapy group. The CT group is superior to the ST group (P<0.001). The surgery combined with chemotherapy (SC) group had the longest mOS and the highest reduced risk of death, but there was no statistical difference.</p><p><strong>Conclusions: </strong>SEER stage, age, radiotherapy, chemotherapy, and surgery were independent prognostic factors in limited-stage patients; CT outperformed ST; the SC group had the longest median survival, but showed no statistical difference.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983331","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":"Short-term outcomes of three- and two-field lymphadenectomy with minimally invasive esophagectomy for esophageal cancer: a propensity score-matching analysis.","authors":"Zeng-Feng Sun, Bo-Shi Fan, Jun-Qiang Liu, Shou-Yin Di, Cai-Ying Yue, Jia-Hua Zhao, Ju-Si Wang, Wei-An Song, Jing Lu, Jia-Le Zhang, Tai-Qian Gong","doi":"10.21037/tcr-23-2356","DOIUrl":"10.21037/tcr-23-2356","url":null,"abstract":"<p><strong>Background: </strong>Whether patients can benefit from three-field lymphadenectomy (3-FL) in minimally invasive esophagectomy (MIE) remains unclear. This study retrospectively compared short-term outcomes between 3-FL and two-field lymphadenectomy (2-FL) in MIE for patients with esophageal cancer (EC) and aimed to evaluate the clinical significance of 3-FL.</p><p><strong>Methods: </strong>There were 284 patients enrolled in the study (124 patients with 3-FL and 160 patients with 2-FL). The cases were matched based on their propensity scores using a matching ratio of 1:1, the nearest neighbor matching protocol, and a caliper of 0.02. Patients were propensity-score matched for sex, cancer location, Age-adjusted Charlson Comorbidity Index (ACCI), and neoadjuvant treatment. The short-term outcomes were postoperative complications, operation characteristics, pathology results and postoperative hospital stay.</p><p><strong>Results: </strong>There were no significant differences in intraoperative hemorrhage, postoperative hospital stay, or postoperative complications between the 2-FL and 3-FL groups. The operation time of the two groups was significantly different (227.1±46.2 <i>vs.</i> 248.5±45.9 min, P=0.001); the operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group. The number of lymphatic nodes (LNs) obtained in the 3-FL group was significantly higher than that in the 2-FL group (31.3±12.9 <i>vs.</i> 54.6±18.0, P<0.001). Pathological N stage was also significantly different (P=0.002); the 3-FL group was more advanced than the 2-FL group.</p><p><strong>Conclusions: </strong>Compared to 2-FL MIE, 3-FL MIE does not increase postoperative complications, can obtain more LNs, and improves the accuracy of tumor LN staging.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983335","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":"Identification of a cancer driver gene-associated lncRNA signature for prognostic prediction and immune response evaluation in clear cell renal cell carcinoma.","authors":"Juncheng Pan, Daorong Hu, Xiaolong Huang, Jie Li, Sizhou Zhang, Jiabing Li","doi":"10.21037/tcr-24-127","DOIUrl":"10.21037/tcr-24-127","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) predominates among kidney cancer cases and is influenced by mutations in cancer driver genes (CDGs). However, significant obstacles persist in the early diagnosis and treatment of ccRCC. While various genetic models offer new hopes for improving ccRCC management, the relationship between CDG-related long non-coding RNAs (CDG-RlncRNAs) and ccRCC remains poorly understood. Therefore, this study aims to construct prognostic molecular features based on CDG-RlncRNAs to predict the prognosis of ccRCC patients, and aims to provide a new strategy to enhance clinical management of ccRCC patients.</p><p><strong>Methods: </strong>This study employed Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses to comprehensively investigate the association between lncRNAs and CDGs in ccRCC. Leveraging The Cancer Genome Atlas (TCGA) dataset, we identified 97 prognostically significant CDG-RlncRNAs and developed a robust prognostic model based on these CDG-RlncRNAs. The performance of the model was rigorously validated using the TCGA dataset for training and the International Cancer Genome Consortium (ICGC) dataset for validation. Functional enrichment analysis elucidated the biological relevance of CDG-RlncRNA features in the model, particularly in tumor immunity. Experimental validation further confirmed the functional role of representative CDG-RlncRNA SNHG3 in ccRCC progression.</p><p><strong>Results: </strong>Our analysis revealed that 97 CDG-RlncRNAs are significantly associated with ccRCC prognosis, enabling patient stratification into different risk groups. Development of a prognostic model incorporating key lncRNAs such as HOXA11-AS, AP002807.1, APCDD1L-DT, AC124067.2, and SNHG3 demonstrated robust predictive accuracy in both training and validation datasets. Importantly, risk stratification based on the model revealed distinct immune-related gene expression patterns. Notably, SNHG3 emerged as a key regulator of the ccRCC cell cycle, highlighting its potential as a therapeutic target.</p><p><strong>Conclusions: </strong>Our study established a concise CDG-RlncRNA signature and underscored the pivotal role of SNHG3 in ccRCC progression. It emphasizes the clinical relevance of CDG-RlncRNAs in prognostic prediction and targeted therapy, offering potential avenues for personalized intervention in ccRCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983363","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 m6A/m5C/m1A/m7G-related classification and risk signature predicts prognosis and reveals immunotherapy inclination in gastric cancer.","authors":"Ruyue Chen, Lixin Jiang","doi":"10.21037/tcr-23-2325","DOIUrl":"10.21037/tcr-23-2325","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is characterized by high morbidity and mortality rates, and the prognosis is not optimistic. Therefore, the search for new biomarkers is crucial. Methylation modifications in RNA modifications play a crucial role in tumors. However, the role of methylation modification of integrated m6A/m5C/m1A/m7G, in GC and its related analysis have not been reported. It still needs to be studied in depth. Our study aims to deepen our understanding of m6A/m5C/m1A/m7G methylation and potentially provide new strategies for GC treatment.</p><p><strong>Methods: </strong>We used TCGA-STAD (The Cancer Genome Atlas-Stomach Adenocarcinoma) as a training set and GSE84433 as a validation set to analyze and determine potential associations between m6A/m5C/m1A/m7G-related genes and clinical risk of GC. In addition, we explored the prognostic value and potential biological mechanisms of m6A/m5C/m1A/m7G-related genes in GC through consistent clustering, differential expression gene identification, enrichment analysis, and immune infiltration analysis. Finally, we constructed m6A/m5C/m1A/m7G-related risk signature (MRRS) to evaluate the correlation between risk grade and survival prognosis, drug sensitivity, and immune infiltration, and validated the validity by immunohistochemical staining.</p><p><strong>Results: </strong>We identified subgroups of C1, C2, and C3 patients by consensus clustering using data from 45 m6A/m5C/m1A/m7G-related genes. The three groups showed significant differences in survival, immune scores, and immune cell infiltration. We then constructed MRRS using least absolute shrinkage and selection operator (LASSO) regression analysis, including <i>SLC5A6, FKBP10, GPC3,</i> and <i>GGH</i>, which could accurately differentiate between high-/low-risk populations. Its accuracy was further validated in the validation set and immunohistochemical staining. These results suggest that m6A/m5C/m1A/m7G are closely related to the GC tumor immune microenvironment, and MRRS has good performance in predicting the survival of GC patients.</p><p><strong>Conclusions: </strong>In this study, we highlighted the association of m6A/m5C/m1A/m7G subtypes with changes in the GC immunotumor microenvironment. We constructed and validated MRRS, which is valuable in predicting survival, immune infiltration and drug sensitivity in GC patients. This helps to deepen our understanding of m6A/m5C/m1A/m7G methylation and potentially provides new strategies for GC treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983277","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":"Identification of a novel cellular senescence-related lncRNA signature for prognosis and immune response in osteosarcoma.","authors":"Honglin Wu, Chuanbao Deng, Xiaoqing Zheng, Yongxiong Huang, Chong Chen, Honglin Gu","doi":"10.21037/tcr-24-163","DOIUrl":"10.21037/tcr-24-163","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence, a novel hallmark of cancer, is associated with patient outcomes and tumor immunotherapy. However, at present, there is no systematic study on the use of cellular senescence-related long non-coding RNAs (CSR-lncRNAs) to predict survival in patients with osteosarcoma. In this study, we aimed to identify a CSR-lncRNAs signature and to evaluate its potential use as a survival prognostic marker and predictive tool for immune response of osteosarcoma.</p><p><strong>Methods: </strong>We downloaded a cohort of patients with osteosarcoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We performed differential expression and co-expression analyses to identify CSR-lncRNAs. We performed univariate and multivariate Cox regression analyses along with the random forest algorithm to identify lncRNAs significantly correlated with senescence. Subsequently, we assessed the predictive models using survival curves, receiver operating characteristic curves, nomograms, C-index, and decision curve analysis. Based on this model, patients with osteosarcoma were divided into two groups according to their risk scores. Then, using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we compared their clinical characteristics to uncover functional differences. We further conducted immune infiltration analyses using estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE), cell-type identification by estimating relative subsets of rna transcripts (CIBERSORT), and single-sample gene set enrichment analysis for the two groups. We also evaluated the expression of the target genes of immune checkpoint inhibitors (ICIs).</p><p><strong>Results: </strong>We identified six lncRNAs that were significantly correlated with senescence and accordingly established a novel cellular senescence-related lncRNA prognostic signature incorporating these lncRNAs. The nomogram indicated that the risk model was an independent prognostic factor that could predict the survival of patients with osteosarcoma. This model demonstrated high accuracy upon validation. Further analysis revealed that patients with osteosarcoma in the low-risk group exhibited better clinical outcomes and enhanced immune infiltration.</p><p><strong>Conclusions: </strong>The six-CSR-lncRNA prognostic signature effectively predicted survival outcomes and patients in the low-risk group might have improved immune infiltration.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983285","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":"MiR-1271-5p promotes the growth and migration of neuroblastoma cells by regulating ACY-1.","authors":"Jun Sun, Xiaowen Zhang, Zimin Chen, Xiaoshuo Ye, Chen Zhang","doi":"10.21037/tcr-24-25","DOIUrl":"10.21037/tcr-24-25","url":null,"abstract":"<p><strong>Background: </strong>Aminoacylase 1 (ACY-1) has been found to be a tumor suppressor gene in neuroblastoma (NB). This study aimed to identify and verify the microRNAs (miRNAs) that may regulate ACY-1 through database prediction analysis, and verify the mutual regulatory effect of miRNA and ACY-1 in NB through cell experiments.</p><p><strong>Methods: </strong>The miRNAs that might bind ACY-1 were predicted and selected by TargetScan, miRTarBase and four other databases, the expression of the predicted miRNAs and ACY-1 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in four groups of clinical samples, and the differentially expressed miRNAs were screened. Then, luciferase vector was constructed according to the <i>ACY-1</i> gene sequence to detect whether ACY-1 binds to the selected miRNA. Then, miR-1271-5p expression was silenced to detect miR-1271-5p function in the growth and migration of NB. Finally, ACY-1 and miR-1271-5p were silenced to change ACY-1 expression, and ACY-1 function in NB and the regulatory role of miR-1271-5p were explored.</p><p><strong>Results: </strong>ACY-1 was downregulated in NB, miR-1271-5p was upregulated in NB, and miR-1271-5p could be targeted to ACY-1. Silencing miR-1271-5p expression can reduce cell viability and inhibit tumor progression. After interfering with ACY-1 expression in cells, cell viability was enhanced, apoptosis was significantly decreased, and migration and invasion were enhanced. After partially restoring ACY-1 expression, the effect of si-ACY-1 on cells was weakened. In SK-N-SH and SH-SY-5Y cells, the miR-1271-5p inhibitor restored ACY-1 expression and improved ACY-1 function.</p><p><strong>Conclusions: </strong>MiR-1271-5p can promote the growth and migration of tumor cells by inhibiting ACY-1 expression in NB.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983291","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":"Telomere-related gene risk model for prognosis prediction in colorectal cancer.","authors":"Hao Chen, Yuhao Pan, Chenhui Lv, Wei He, Dingting Wu, Qijia Xuan","doi":"10.21037/tcr-24-43","DOIUrl":"10.21037/tcr-24-43","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the third-most prevalent cancer globally. The biological significance of telomeres in CRC carcinogenesis and progression is underscored by accumulating data. Nevertheless, not much is known about how telomere-related genes (TRGs) affect CRC prognosis. Therefore, the aim of this study was to investigate the role of TRGs in CRC prognosis.</p><p><strong>Methods: </strong>We retrospectively obtained the expression profiles and clinical data of CRC patients from public databases. Utilizing least absolute shrinkage and selection operator (LASSO) regression analysis, we created a telomere-related risk model to predict survival outcomes, identifying ten telomere-related differentially expressed genes (TRDEGs). Based on TRDEGs, we stratified patients from The Cancer Genome Atlas (TCGA) into low- and high-risk subsets. Subsequently, we conducted comprehensive analyses, including survival assessment, immune cell infiltration, drug sensitivity, and prediction of molecular interactions using Kaplan-Meier curves, ESTIMATE, CIBERSORT, OncoPredict, and other approaches.</p><p><strong>Results: </strong>The model showed exceptional predictive accuracy for survival. Significant differences in survival were observed between the two groups of participants grouped according to the model (P<0.001), and this difference was further confirmed in the external validation set (GSE39582) (P=0.004). Additionally, compared to the low-risk group, the high-risk group exhibited significantly advanced tumor node metastasis (TNM) stages, lower proportions of activated CD4⁺ T cells, effector memory CD4⁺ T cells, and memory B cells, but increased ratios of M2 macrophages and regulatory T cells (Tregs), elevated tumor immune dysfunction and exclusion (TIDE) scores, and diminished sensitivity to dabrafenib, lapatinib, camptothecin, docetaxel, and telomerase inhibitor IX, reflecting the signature's capacity to distinguish clinical pathological characteristics, immune environment, and drug efficacy. Finally, we validated the expression of the ten TRDEGs (<i>ACACB</i>, <i>TPX2</i>, <i>SRPX</i>, <i>PPARGC1A</i>, <i>CD36</i>, <i>MMP3</i>, <i>NAT2</i>, <i>MMP10</i>, <i>HIGD1A</i>, and <i>MMP1</i>) through quantitative real-time polymerase chain reaction (qRT-PCR) and found that compared to normal cells, the expression levels of <i>ACACB</i>, <i>HIGD1A</i>, <i>NAT2</i>, <i>PPARGC1A</i>, and <i>TPX2</i> in CRC cells were elevated, whereas those of <i>CD36</i>, <i>SRPX</i>, <i>MMP1</i>, <i>MMP3</i>, and <i>MMP10</i> were reduced.</p><p><strong>Conclusions: </strong>Overall, we constructed a telomere-related biomarker capable of predicting prognosis and treatment response in CRC individuals, offering potential guidance for drug therapy selection and prognosis prediction.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983296","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":"Effect and mechanism of curcumin on colon cancer cell senescence through early growth response 1 (EGR1).","authors":"Dan Xu, Linjun Li, Zhaomin Yu","doi":"10.21037/tcr-24-26","DOIUrl":"10.21037/tcr-24-26","url":null,"abstract":"<p><strong>Background: </strong>The expression level of early growth response 1 (EGR1) is elevated in colon cancer (CC) tissues and is closely associated with poor prognosis in colorectal cancer. However, the role of EGR1 as a transcription factor (TF) influencing cell senescence in the progression of CC remains largely unexplored. This study aims to investigate the impact of curcumin on colorectal cancer cell senescence by modulating EGR1.</p><p><strong>Methods: </strong>Genes associated with cell senescence were obtained from a public database, and ChIP-X predicted TFs were utilized. The R2 database was employed to examine the relationship between gene expression and survival. CC cell lines were transfected with plasmids to achieve stable expression. Stable transfected cell lines were screened, and changes in RNA and protein expression were assessed using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) analysis. Senescence levels were measured by SA-β-Gal staining. Cell proliferation and invasion capabilities were evaluated through soft agar and Matrigel invasion assays. Molecular docking was used to predict the interaction between curcumin and EGR1. Gene activity changes were detected using a dual luciferase reporter gene assay.</p><p><strong>Results: </strong>The results indicated that EGR1 was overexpressed in CC tissues and correlated with poor prognosis. As a TF, EGR1 negatively regulated the expression of telomerase reverse transcriptase (TERT) and sirtuin 6 (SIRT6) genes associated with cell senescence. Knocking down EGR1 increased the rate of cell senescence and inhibited cell proliferation and invasion. Curcumin inhibited the transcriptional activity of EGR1, thereby promoting cell senescence and inhibiting tumor progression.</p><p><strong>Conclusions: </strong>In conclusion, curcumin hampers the activity of TF EGR1, affecting the transcription and translation of target genes TERT and SIRT6, thus promoting cell senescence and inhibiting CC cell proliferation. These findings provide potential insights for targeted therapy of CC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983357","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 key pathogenic mechanisms and potential intervention targets for recurrence after laryngeal cancer treatment through bioinformatics screening.","authors":"Laiyan Liu, Jiebin Wu","doi":"10.21037/tcr-24-1015","DOIUrl":"10.21037/tcr-24-1015","url":null,"abstract":"<p><strong>Background: </strong>Laryngeal cancer (LC), a prevalent malignant tumor of the head and neck, is characterized by a high rate of postoperative recurrence and significant treatment challenges upon recurrence, severely impacting patients' quality of life. There is a pressing need for effective biomarkers in clinical practice to predict the risk of LC recurrence and guide the development of personalized treatment plans. This study uses bioinformatics methods to explore potential biomarkers for LC recurrence, focusing on key genes and exploring their functions and mechanisms of action in LC recurrence. The aim is to provide new perspectives and evidence for clinical diagnosis, prognostic evaluation, and targeted treatment of LC.</p><p><strong>Methods: </strong>Gene expression profiles from the GSE25727 data set in the Gene Expression Omnibus database were analyzed to detect the differentially expressed genes (DEGs) between the tumor tissues of postoperative recurrent and non-recurrent early stage LC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted. A protein-protein interaction (PPI) network and transcription factor (TF)-DEG-microRNA (miRNA) network were developed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, with key genes selected using the Molecular Complex Detection (MCODE) plugin. A Gene Set Enrichment Analysis (GSEA) was carried out to investigate the possible mechanisms of the key genes. A retrospective analysis was conducted using the clinical data of 83 LC patients. Immunohistochemical staining was used to examine the transcription level of the key genes in the LC tumor tissues and the factors affecting postoperative recurrence.</p><p><strong>Results: </strong>A total of 248 upregulated and 34 downregulated DEGs were identified in the GSE25727 data set. The PPI network analysis identified a significant module and five candidate genes (i.e., <i>RRAGA</i>, <i>SLC38A9</i>, <i>WDR24</i>, <i>ATP6V1B1</i>, and <i>LAMTOR3</i>). The construction of the TF-DEG-miRNA network indicated that <i>ATP6V1B1</i> might be regulated by one TF and interact with 17 miRNAs. The KEGG and GSEA analyses suggested that <i>ATP6V1B1</i> may influence LC recurrence through the involvement of pro-inflammatory and pro-fibrotic mediators, glutathione metabolism, matrix metalloproteinases, immune regulation, and lymphocyte interactions. The recurrence rate of the 83 LC patients included in the study was 19.3% (16/83). The immunohistochemistry results indicated that ATP6V1B1 was highly expressed in patients with recurrent LC. The univariate and multivariate logistic regression analyses revealed that tumor stage T3 (P=0.04), tumor stage T4 (P=0.01), and a high expression of ATP6V1B1 (P=0.02) were risk factors for recurrence after surgical treatment in LC patients.</p><p><strong>Conclusions: </strong>The key genes and signaling pathways identified through t","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983287","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}