Translational cancer research最新文献

{"title":"Overexpression of <i>LINC00880</i> promotes colorectal cancer growth.","authors":"Ge Gao, Peiwen Xu, Chunyu Yang, Mengyuan Qian, Qingwen Wang, Surui Yao, Yuan Yin, Zhaohui Huang, Zehua Bian","doi":"10.21037/tcr-2025-54","DOIUrl":"https://doi.org/10.21037/tcr-2025-54","url":null,"abstract":"<p><strong>Background: </strong>Research has revealed that long non-coding RNAs (lncRNAs) are intimately associated with the occurrence, development, and metastasis of tumors through their regulation of gene expression. The lncRNA <i>LINC00880</i> is important for colorectal cancer (CRC) occurrence and development. Our research aimed to explore the roles of <i>LINC00880</i> in CRC progression.</p><p><strong>Methods: </strong>The expression of <i>LINC00880</i> in CRC cells and tissues was first measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the prognosis of CRC patients was then investigated using the Kaplan-Meier method. The impacts of <i>LINC00880</i> on CRC growth were evaluated by a series of <i>in vitro</i> and <i>in vivo</i> assays. Mechanistically, RNA sequencing (RNA-seq) technology and transcriptome analysis experiments were employed to validate the impact of <i>LINC00880</i> on cell cycle pathway.</p><p><strong>Results: </strong>In this study, we have demonstrated, for the first time, that <i>LINC00880</i> is significantly overexpressed in CRC and is associated with poor patient survival. Functional assays indicated that <i>LINC00880</i> promotes the growth of CRC cells both <i>in vitro</i> and <i>in vivo</i>. Furthermore, RNA-seq has revealed the impact of <i>LINC00880</i> on the cell cycle and DNA replication pathways, and identified MCM3 as a potential downstream target of <i>LINC00880</i>.</p><p><strong>Conclusions: </strong>Our findings indicate that <i>LINC00880</i> is upregulated in CRC and promotes tumor growth.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2926-2939"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317950","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":"Significant weight gain benefits of nanocrystalline megestrol acetate for patients with cancer anorexia-cachexia syndrome.","authors":"Xue Cheng, Kang Pan, Qing Li, Xin Jin, Chengsong Cao, Yong Liu","doi":"10.21037/tcr-2025-866","DOIUrl":"https://doi.org/10.21037/tcr-2025-866","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cancer anorexia-cachexia syndrome (CACS) is a multifactorial syndrome characterized by weight loss and muscle wasting that leads to impaired physical function, decreased tolerance to anticancer therapies, and reduced survival rates. Megestrol acetate (MA) is an important pharmacological intervention for CACS. Nanocrystalline MA (MA-ES), leveraging nanocrystal technology, enhances bioavailability and absorption rates. Previous research has demonstrated that MA-ES could result in a more significant weight increase than non-MA-ES. However, its efficacy and safety in Chinese patients with cancer require further evaluation and validation in real-world clinical settings. The purpose of this study was to evaluate the therapeutic efficacy and safety of MA-ES and MA tablets in hormone-insensitive patients with CACS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This prospective, multi-cohort, multicenter, real-world clinical study compared MA-ES and MA tablets in terms of efficacy and safety for hormone-insensitive patients with CACS (excluding breast cancer, endometrial cancer, and prostate cancer). The MA-ES group received 5 mL/day (625 mg/day), while the MA tablet group received 800 mg/day. CACS patients who completed three cycles of MA-ES at 5 mL/day or MA tablets at 800 mg/day were included in the propensity score matching (PSM) analysis (one cycle was defined as 28 days, with ≥21 days considered as completion of one cycle). PSM (1:2 ratio, caliper width 0.1) was used to mitigate the confounding factors. Patients were treated for three consecutive cycles, with each cycle lasting 4 weeks. The primary endpoint was the change in body weight from baseline at 12 weeks. Additionally, appetite, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scores, and safety were also evaluated. The standardized mean differences (SMDs) before and after PSM were calculated to examine the balance of covariate distributions between two groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Between October 15, 2024 and February 28, 2025, 126 patients met the screening criteria and were enrolled in the analysis, with 76 in the MA-ES group and 50 in the MA tablet group. SMD of each matched variable was less than 0.10. At week 12, the MA-ES group exhibited an average weight gain of 4.49 kg, significantly higher than the 2.10 kg observed in the MA tablet group, with a mean difference of 2.39 kg (95% confidence interval: 1.33-3.45; P&lt;0.001). Furthermore, at week 12, the MA-ES group demonstrated significantly greater proportions of participants with improved appetite (81.6% &lt;i&gt;vs.&lt;/i&gt; 42.0%; P&lt;0.001) and enhanced global health status (P&lt;0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;MA-ES administered at 625 mg/day for over three cycles may offer superior weight gain benefits compared to the conventional MA tablets at 800 mg/day in hormone-insensitive patients with CACS. Moreover, MA-ES appears to provide more signifi","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3212-3225"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317958","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":"Development of a prognostic nomogram and risk factor analysis for survival in <i>H. pylori</i>-positive non-cardia gastric adenocarcinoma patients.","authors":"Jing Wu, Xiancai Du, Wenwen Chen, Ting Ma, Lu Tian, Hong Zhang, Guanhua Wang, Wenjun Yang","doi":"10.21037/tcr-24-1776","DOIUrl":"https://doi.org/10.21037/tcr-24-1776","url":null,"abstract":"<p><strong>Background: </strong>Currently, there is limited research on the prognosis and influencing factors of non-cardia gastric adenocarcinoma (NCGAC) patients. This study aims to explore the factors influencing overall survival (OS) in <i>Helicobacter pylori</i> (<i>H. pylori</i>)-positive NCGAC patients and to develop a nomogram model to provide guidance for clinicians.</p><p><strong>Methods: </strong>We retrospectively analyzed clinicopathological data from 413 <i>H. pylori</i>-positive NCGAC patients who underwent radical gastrectomy at the General Hospital of Ningxia Medical University. The dataset was randomly split into a training cohort (70%) and a validation cohort (30%). Univariate Cox proportional hazards regression analysis was used to identify prognostic factors, and factors with multicollinearity [variance inflation factor (VIF) >4] were excluded using the VIF. Factors of interest and those with P<0.05 were included in the multivariate Cox proportional hazards regression model. A nomogram prediction model was constructed based on factors with P<0.05. The model's performance was finally assessed using the area under the receiver operating characteristic curve (AUC) and calibration curves. The Kaplan-Meier survival curves visualize the impact of independent prognostic factors.</p><p><strong>Results: </strong>Univariate Cox regression analysis was performed on the training cohort to select variables with P<0.5, including alcohol consumption, tumor size, differentiation grade, lymph node metastasis, tumor (T) stage, node (N) stage, and tumor node metastasis (TNM) stage. Multicollinearity was assessed, and covariates with VIF >4, such as lymph node metastasis, were excluded. The remaining factors were included in the multivariate Cox regression model. Significant variables (P<0.05), including alcohol consumption, differentiation grade, and T stage, were used to construct a nomogram, which showed a concordance index (C-index) of 0.727 in the training cohort and 0.728 in the validation cohort. The model's performance was validated with AUC and calibration curves (training cohort: 1-year AUC: 0.74, 3-year AUC: 0.78, 4-year AUC: 0.80; validation cohort: 1-year AUC: 0.67, 3-year AUC: 0.71, 4-year AUC: 0.72). Kaplan-Meier survival curves illustrated the impact of independent prognostic factors.</p><p><strong>Conclusions: </strong>We developed a nomogram to predict survival in <i>H. pylori</i>-positive NCGAC patients, based on alcohol consumption, tumor differentiation, and T stage. The model showed strong predictive performance, with C-index values of 0.727 in the training cohort and 0.728 in the validation cohort. AUC values and calibration curves further confirmed its accuracy, suggesting the nomogram is a reliable tool for predicting prognosis and guiding treatment decisions.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2822-2834"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317907","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":"Extracellular vesicles isolated from SphK1 inhibitor SKI II-medium restrain the migration of colorectal cancer.","authors":"Chunyan Xu, Yingbin Hu, Guodong Dai, Yan Chen, Chengxia Liu","doi":"10.21037/tcr-24-2152","DOIUrl":"https://doi.org/10.21037/tcr-24-2152","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is a chronic disease particularly detrimental to human health. Although there have been many studies on colorectal cancer and extracellular vesicles (EVs), it is unknown whether SKI II, an inhibitor of sphingosine kinase 1 (SphK1), uses EVs as transporters to inhibit colorectal cancer migration. This research aimed to investigate whether EVs, which were isolated from SphK1 inhibitor SKI II-medium, affected on E-cadherin and vimentin and the cell migration of colorectal cancer cells.</p><p><strong>Methods: </strong>EVs were extracted from RKO cells using an exosome extraction and purification kit, and the extracted EVs were identified to evaluate whether the EVs extracted by this kit met the experimental requirements. ^RKOEVs were extracted from RKO exosom-free serum culture medium, and ^RKO-SKEVs were extracted from RKO exosom-free serum culture medium with SKI II intervention. PKH67-labeled EVs were added to the cells. EVs inhibitor GW4869, ^RKOEVs, and ^RKO-SKEVs were used to intervene in RKO cells, and ^RKOEVs and ^RKO-SKEVs were used to intervene in HT29 cells. The E-cadherin and vimentin expression were tested by western blotting. Transwell assay was used to detect cell migration ability.</p><p><strong>Results: </strong>Compared with the control group, after GW4869 treatment, E-cadherin was increased, vimentin was decreased, and the number of migrating cells was decreased. After ^RKOEVs intervention, the expression of E-cadherin, vimentin and cell migration number were opposite. Compared with ^RKOEVs intervention in RKO cells, E-cadherin was increased, vimentin was decreased and the number of migrating cells decreased after ^RKO-SKEVs intervention. Similarly, compared with ^RKOEVs intervention in HT29 cells, after ^RKO-SKEVs intervention, E-cadherin was increased, vimentin was decreased, and the number of migrating cells decreased.</p><p><strong>Conclusions: </strong>EVs isolated from SphK1 inhibitor SKI II-medium affect E-cadherin and vimentin expression in colorectal cancer and inhibit cell migration.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2594-2602"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317915","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":"Development of a prognostic model for overall survival in neuroblastoma based on Schwann cell-specific genes, clinical predictors, and MYCN amplification.","authors":"Zexi Li, Jing Liu, Yurui Wu","doi":"10.21037/tcr-24-2048","DOIUrl":"https://doi.org/10.21037/tcr-24-2048","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Neuroblastoma (NBL) is a common pediatric malignancy with diverse prognoses influenced by multiple factors. Accurate overall survival (OS) predictions are essential for guiding treatment. However, the contribution of specific cell types within the tumor microenvironment (TME), which significantly influence disease progression, is often overlooked. This study aimed to develop an NBL prognostic model that incorporates TME, genetic, and clinical factors to improve prediction accuracy and clinical relevance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data were collected from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database (n=106, test set) and the Gene Expression Omnibus (GEO) database (n=238, train set). Including clinical details such as MYCN amplification, International NBL Staging System (INSS) stage, age at diagnosis, and OS outcomes. Additionally, single-cell RNA sequencing (scRNA-seq) data from 16 NBL patients (160,910 cells) were included to improve model precision. Uniform manifold approximation and projection (UMAP) was utilized for cell clustering, while weighted gene co-expression network analysis (WGCNA) helped identify cell-type-specific modules. Prognostic genes were pinpointed using univariate and multivariate Cox regression analyses, which also served to refine the model by integrating essential clinical variables and molecular markers. The model's effectiveness was assessed through Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and calibration plots. Additional evaluations included immune cell infiltration and drug sensitivity analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;MYCN amplification was present in 79.4% of patients in the train set and 79.2% of patients in the test set, and the majority of patients in both cohorts were classified as Stage 4. The median age at diagnosis was 399.5 days in the train set and 1,069 days in the test set. Key findings demonstrate that Schwann cell-specific genes (&lt;i&gt;CALR&lt;/i&gt;, &lt;i&gt;KLF10&lt;/i&gt;, &lt;i&gt;UBL3&lt;/i&gt;) considerably affect survival outcomes in NBL patients. The initial model showed robust predictive accuracy in the train set with areas under the curve (AUCs) of 0.832 and acceptable performance in the test set with AUC of 0.777. A refined model, incorporating three genes, two clinical indicators (age and INSS stage), and MYCN amplification, exhibited enhanced accuracy with AUC of 0.857. Differences in immune cell expression between high-risk and low-risk groups were noted, alongside significant disparities in drug sensitivity, indicating lower half maximal inhibitory concentration (IC50) values for targeted therapies in the high-risk group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study developed a model for predicting OS in NBL by integrating Schwann cell-specific genes, clinical factors, and the TME. The model highlights the importance of specific cellular contributions to prognosis and provides a more person","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2677-2689"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317943","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 role of tumor microenvironment and immune- and autophagy-related genes in colorectal adenocarcinoma.","authors":"Miao Zhang, Wen Jin, Lei Cao, Yanwei Gao, Yongsheng Wang, Jialin Wang","doi":"10.21037/tcr-24-1708","DOIUrl":"https://doi.org/10.21037/tcr-24-1708","url":null,"abstract":"<p><strong>Background: </strong>Colorectal adenocarcinoma (COADREAD) is the second most common cause of cancer-associated deaths. Immunity and autophagy play a key role in the development and progression of COADREAD, but the specific mechanisms have not been fully elucidated. We aimed to explore immune- and autophagy-related genes (IARGs) to establish prognostic risk assessment and clinical prediction models and to understand the molecular basis of COADREAD.</p><p><strong>Methods: </strong>Transcriptomic and clinical data from colon (COAD) and rectal cancers (READ) were obtained from TCGA and GEO databases, including 460 COADREAD cases and validation cohorts (GSE161158/GSE17536). Immune-related (IRGs) and autophagy-related genes (ARGs) were integrated to identify 22 immune-autophagy-related genes (IARGs). Molecular subtypes were constructed via consensus clustering of IARGs, followed by gene set variation analysis (GSVA) to explore pathway activity. Differentially expressed immune-autophagy-related genes (IARDEGs) were identified using limma and subjected to functional enrichment [Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)]. A prognostic risk model was developed via LASSO and Cox regression, validated in external cohorts. Immune infiltration was assessed using ssGSEA, and a nomogram integrating clinicopathological features was established. Statistical analyses were performed in R (v4.2.2), with significance at P<0.05.</p><p><strong>Results: </strong>The IARG data could be used to distinguish between cancerous and normal specimens of COADREAD. <i>VEGFA, BIRC5</i>, and <i>BID</i> genes were highly expressed in COADREAD, while the expression of <i>TNFSF10</i> was low. Most of the IARGs were positively correlated with COADREAD. The GSVA results of four classes of C4 verified that the clustering effect was best. More IARGs, such as <i>CXCR4, CCL2</i>, and <i>CTSB</i>, were in the C4 class than the C1 class. In the risk model, the T cell and B cell receptor pathways were substantially upregulated in patients in the low-risk group. The risk score greatly differed with the different expression levels of key immune checkpoints and immune cell infiltration, and the levels of immune cells were higher in the low-risk group.</p><p><strong>Conclusions: </strong>In this study, bioinformatic analysis proved that immune-a1-related genes could be used to distinguish between normal and COADREAD specimens and that immunity and autophagy are associated with low-risk COADREAD; therefore, these genes have the potential to improve clinical predictions of COADREAD risk.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2835-2857"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317952","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 high expression of Long noncoding RNA TEX41 promotes the proliferation, migration, and invasion of hepatocellular carcinoma.","authors":"Zhihao Li, Hui Xu, Hao Chen, Liang Chen, Hong Zang, Yi Qian","doi":"10.21037/tcr-2025-812","DOIUrl":"https://doi.org/10.21037/tcr-2025-812","url":null,"abstract":"<p><strong>Background: </strong>Long noncoding RNA (lncRNA) TEX41 has been linked to the progression of various kinds of cancers. In this study, the expression of lncRNA TEX41 and cell biological function of lncRNA TEX41 were examined in the context of hepatocellular carcinoma (HCC) to measure their ability to predict HCC progression. The relationship between lncRNA TEX41, miR-200a-3p, and potential downstream target gene <i>BIRC5</i> was further explored. The purpose of the present study was to provide a new theoretical basis for the diagnosis and treatment of HCC.</p><p><strong>Methods: </strong>The GEPIA2, starBase and Gene Expression Omnibus (GEO) databases were used to analyze the biological functions and molecular mechanisms of lncRNA TEX41. The expression of lncRNA TEX41 in clinical tissue samples and cell lines was detected via quantitative real-time polymerase chain reaction (qRT-PCR). We investigated the impact of TEX41 on the proliferation, migration, and invasion of HCC cells, as well as its underlying mechanism.</p><p><strong>Results: </strong>The expression levels of lncRNA TEX41 in HCC tissues are higher than those in adjacent tissues. The expression of lncRNA TEX41 was associated with lymph node metastasis and tumor-node-metastasis (TNM) staging in HCC patients. Silencing lncRNA TEX41 inhibited the proliferation, migration, and invasion of HCC cell lines. Low expression of lncRNA TEX41 may have affected epithelial-mesenchymal transition (EMT) in HCC cell lines. There may be a functional relationship between lncRNA TEX41 and miR-200a-3p-BIRC5.</p><p><strong>Conclusions: </strong>LncRNA TEX41 may promote the progression of HCC through the miR-200a-3p-BIRC5 axis.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3175-3185"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317961","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":"Ubiquitin-specific peptidase 20 affects immune cell infiltration by regulating prostaglandin E2 on intraperitoneal metastasis model of colorectal cancer.","authors":"Yang Hua, Xiukun Ma, Xinyu Zhao, Xiaomeng Wei, Xiaojing Mu, Botao Wang, Xiangfei Yuan","doi":"10.21037/tcr-2024-2194","DOIUrl":"https://doi.org/10.21037/tcr-2024-2194","url":null,"abstract":"<p><strong>Background: </strong>Ubiquitin-specific peptidase 20 (USP20) acts as oncogene or tumor suppressor gene in different types of cancer. But there are only a few reports about the effect of USP20 on colorectal cancer (CRC). This study aims to further explore the novel molecular mechanisms of USP20 in intraperitoneal metastasis of CRC.</p><p><strong>Methods: </strong>First, bioinformatics analyses were performed to discover the association between USP20 expression and the clinical characteristics of CRC. Subsequently, the mouse model was constructed using a USP20 knockout (USP20-KO) colon cell line to validate the effects of USP20 on intraperitoneal metastasis and immune cell infiltration. And then metabolomics study was performed on the USP20-KO cells to find the novel mechanisms of USP20. Finally, the relationship of prostaglandin E2 (PGE2) and USP20 was identified by enzyme-linked immunosorbent assay (ELISA) and Western blotting experiments.</p><p><strong>Results: </strong>Bioinformatics analyses showed that the USP20 expression was significantly upregulated in CRC and affected immune cell infiltration. The animal model study revealed that the intraperitoneal metastasis of tumor cell was inhibited by knocking out USP20, and the expression of USP20 could affect the proportions of CD8⁺ T cells and myeloid-derived suppressor cells (MDSCs) in tumor tissue and ascites. Metabolomics study found that PGE2 should be the key metabolite regulated by USP20 for affecting immune cell infiltration. Finally, it was validated that the expressions of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and microsomal prostaglandin E synthase-1 (mPGES-1) were regulated by the USP20 related ubiquitin-proteasome pathway.</p><p><strong>Conclusions: </strong>The USP20 expression is significantly upregulated in CRC, and can promote tumor metastasis by affecting immune cell infiltration. As an important tumor metabolite which can influence immune cell infiltration, PGE2 is regulated by USP20 through the protein degradation of mPGES-1 and 15-PGDH mediated by proteasome.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3149-3160"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317966","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 value of lactate dehydrogenase to albumin ratio in first-line chemoimmunotherapy for locally advanced or metastatic non-small cell lung cancer.","authors":"Bohua Wei, Hao Cui, Kun Qian, Kejian Shi, Peilong Zhang, Yi Zhang","doi":"10.21037/tcr-2024-2577","DOIUrl":"https://doi.org/10.21037/tcr-2024-2577","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) combined with platinum-based dual chemotherapy has been widely used as first-line treatment modality for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). This study aimed to investigate the potential value of lactate dehydrogenase to albumin ratio (LAR) in predicting treatment efficacy in these patients.</p><p><strong>Methods: </strong>A total of 110 patients with locally advanced or metastatic NSCLC treated with first-line chemoimmunotherapy between January 2021 and March 2024 at Xuanwu Hospital, Capital Medical University, were enrolled. In different subgroups, according to a 50% ratio, patients were divided into high baseline LAR and low baseline LAR groups and their progression-free survival (PFS) was compared. Then univariate and multivariate cox hazard analyses were conducted to identify independent predictors of PFS. Finally, a nomogram was constructed to intuitively show the results.</p><p><strong>Results: </strong>The PFS of patients with high baseline LAR was significantly shorter than that of patients with low baseline LAR, regardless of whether in the overall patient population, different staging subgroups, or different pathological type subgroups (P<0.01). Based on multivariate cox analysis, age, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) and baseline LAR were identified as independent indicators affecting PFS. Then a nomogram based on these three predictors was constructed accordingly and its C-index was 0.801 [95% confidence interval (CI): 0.747-0.855].</p><p><strong>Conclusions: </strong>The present study demonstrates that LAR is a useful prognostic predictor in patients with locally advanced or metastatic NSCLC treated with first-line chemoimmunotherapy in clinical practice.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2956-2965"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317954","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":"Sublobar resection is non-inferior to lobectomy in octogenarians and older with stage Ia non‑small cell lung cancer.","authors":"Chuxu Wang, Yiwei Hu, Bo Min, Zilong Tang, Guodong Hu, Chengxiang Wang, Yaqin Wang, Haibo Hu, Xiaohua Zuo","doi":"10.21037/tcr-2024-2575","DOIUrl":"https://doi.org/10.21037/tcr-2024-2575","url":null,"abstract":"<p><strong>Background: </strong>For individuals aged 80 years and older with early-stage non-small cell lung cancer (NSCLC), prior research has indicated that surgical intervention accompanied by lymphadenectomy may offer superior long-term survival outcomes compared to radiotherapy; however, the selection of the appropriate surgical approach continues to be a subject of debate. So, our aim is to compare overall survival (OS) differences between two surgical modalities (lobectomy and sublobar resection) in patients aged 80 years and older with pathological stage Ia NSCLC according to the 8th edition of the tumor-node-metastasis (TNM) staging system.</p><p><strong>Methods: </strong>Patients aged ≥80 years with pathological stage Ia (T1N0M0) NSCLC from 2004 to 2021 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were assigned to either the lobectomy or sublobar resection group. Optimal cutoff values for lymph nodes examined (LNE) were determined using X-Tile software, and lymph node status was classified into low dissection (1 to 5 lymph nodes) and high dissection (6 or more lymph nodes) groups. Confounding factors were controlled through propensity score matching (PSM) analysis, and OS results were analyzed using the Kaplan-Meier method. Survival-related factors were identified using multivariate Cox regression analysis.</p><p><strong>Results: </strong>A total of 1,735 patients were identified, with 30.0% in the sublobar resection group and 70.0% in the lobectomy group. The OS of the lobectomy group was significantly higher than that of the sublobar resection group (P=0.02). The 1-, 3-, and 5-year OS rates were 90.79%, 71.38%, and 56.60% for the sublobar resection group, respectively, compared to 89.87%, 76.88%, and 60.94% for the lobectomy group. In multivariate Cox regression analysis, the high lymph node dissection group demonstrated better prognosis [hazard ratio (HR) =0.796; 95% confidence interval (CI): 0.690-0.919; P=0.002]. Younger age, female sex, adenocarcinoma histology, and smaller tumor sizes were independent prognostic factors for improved OS. After PSM, no significant difference in OS was observed between the two groups (P=0.28), with 1-, 3-, and 5-year OS rates of 87.69%, 76.43%, and 56.41% in the lobectomy group, and 90.21%, 70.54%, and 55.65% in the sublobar resection group. Multivariate Cox regression indicated that the high lymph node dissection group had a better prognosis (HR =0.765; 95% CI: 0.620-0.944; P=0.01). Additionally, younger age and female sex were identified as independent prognostic factors for better OS.</p><p><strong>Conclusions: </strong>For patients aged 80 years and older diagnosed with stage Ia NSCLC, it is recommended that sublobar resection be performed in conjunction with the dissection of a minimum of six lymph nodes.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2966-2980"},"PeriodicalIF":1.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317960","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}