Translational cancer research最新文献

{"title":"Upregulation of CKS2 in immunosuppressive cells is associated with metastasis and poor prognosis in prostate cancer: a single-cell RNA-sequencing analysis.","authors":"Xiaoxing Liang, Renlun Huang, Xinyue Ping, Wei Deng, Songtao Xiang, Zhichao Wang, Jiadong Cao","doi":"10.21037/tcr-23-2100","DOIUrl":"https://doi.org/10.21037/tcr-23-2100","url":null,"abstract":"<p><strong>Background: </strong>Metastasis worsens prostate cancer (PCa) prognosis, with the immunosuppressive microenvironment playing a key role in bone metastasis. This study aimed to investigate how an immunosuppressive environment promotes PCa metastasis and worsens prognosis of patients with PCa.</p><p><strong>Methods: </strong>Candidate oncogenes were identified through analysis of the Gene Expression Omnibus (GEO) database. A prognostic model was developed for the purpose of identifying target genes. A single-cell RNA sequencing data from GEO database was used to analyze the localization of target genes in the tumor microenvironment. A pan-cancer analysis was conducted to study the cancer-causing potential of target genes across different types of tumors.</p><p><strong>Results: </strong>Fifty-one genes were found to be differentially expressed in bone metastasis compared to non-metastatic PCa, with CKS2 identified as the most significant gene associated with poor prognosis. CKS2 was shown to be linked to an immunosuppressive microenvironment and osteoclastic bone metastases, as shown by its negative correlation with immune cell infiltration and osteoblast-related gene expression. Moreover, CKS2 was found in immunosuppressive cells and was linked to bone metastasis in PCa. It was also overexpressed in different types of tumors, making it as an oncogenic gene.</p><p><strong>Conclusions: </strong>This research offers a new perspective on the potential utility of CKS2 as a therapeutic target for the prevention of metastatic PCa.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296284","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":"AIBP promotes cell proliferation and migration through the ERK1/2-MAPK signaling pathway in hepatocellular carcinoma.","authors":"Tianxin Huang, Sijia Ge, Wei Huang, Tao Ma, Yu Sheng, Jing Chen, Shuzhen Wu, Zhaoxiu Liu, Cuihua Lu","doi":"10.21037/tcr-23-2101","DOIUrl":"https://doi.org/10.21037/tcr-23-2101","url":null,"abstract":"<p><strong>Background: </strong>As a highly aggressive cancer, hepatocellular carcinoma (HCC) is often found at an advanced stage and has a poor prognosis. Therefore, in addition to the surgical treatment of HCC, the drug therapy for HCC is still under continuous exploration. The primary apolipoprotein of high-density lipoproteins (HDLs) is apolipoprotein A-I binding protein (AIBP), which has a significant impact on cholesterol metabolism, angiogenesis, and a wide range of inflammatory disorders, including cancer. The AIBP function in HCC is, however, yet unknown. This study aims to reveal the underlying mechanisms of AIBP influencing HCC proliferation and migration through mitogen-activated protein kinase (MAPK) pathways.</p><p><strong>Methods: </strong>AIBP expression and its clinical prognostic association were investigated using The Cancer Genome Atlas (TCGA) data. The AIBP expression was studied in human HCC tissues using immunohistochemistry (IHC) and western blotting. Colony formation assays (CFAs) and cell counting kit-8 (CCK-8) were used to determine <i>in vitro</i> cell proliferation. Cell migration and invasion were evaluated using wound-healing and transwell assays. A xenograft tumor model was employed to investigate HCC cell proliferation in nude mice.</p><p><strong>Results: </strong>Tissues from HCC patients had much increased AIBP expression compared to nearby normal tissues. The prognosis for patients was bleak when AIBP expression was high. When AIBP was overexpressed in SMMC-7721 cells, the cells may become more proliferative, migrative, and invasive. In contrast, the HCC-LM3 cells' ability to proliferate, migrate, and invade was drastically decreased once AIBP was knocked down <i>in vitro</i>. Furthermore, <i>in vivo</i> research showed that AIBP overexpression may enhance cell proliferation in HCC. Finally, we discovered that AIBP could control the MAPK signaling pathway-involved genes expression, including P-MEK, MEK, c-Myc, P-ERK1/2, and ERK1/2, and that GDC-0994, a specific ERK1/2 inhibitor, could suppress the AIBP overexpression induced cell migration and proliferation abilities.</p><p><strong>Conclusions: </strong>These findings demonstrated that the ERK/MAPK signaling pathway might be stimulated by AIBP in HCC tissues, leading to increased cell invasion, migration, and proliferation. It was hypothesized that AIBP might act as a useful prognostic and diagnostic marker for HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296228","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 hub genes and key modules in laryngeal squamous cell carcinoma.","authors":"Hongyue Li, Shaojun Bo, Yutian Guo, Tiantian Wang, Yangwang Pan","doi":"10.21037/tcr-24-104","DOIUrl":"10.21037/tcr-24-104","url":null,"abstract":"<p><strong>Background: </strong>Laryngeal squamous cell carcinoma (LSCC) is the prominent cancer in head and neck, which greatly affects life quality of patients. The pathogenesis of LSCC is not clear. Presently, the LSCC treatments include chemotherapy, surgery and radiotherapy; however, these methods have poor efficacy in patients with recurrent and persistent cancer. Therefore, the study identified the hub genes accompanied with LSCC, which may be a potential therapeutic target in the future.</p><p><strong>Methods: </strong>We extracted whole transcriptome high-throughput sequencing (HTS) LSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and calculate differentially expressed genes (DEGs) between LSCC and normal samples using statistical software RStudio. Through weighted gene co-expression network analysis (WGCNA), enrichment examination of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) functions, and examination of protein-protein interaction (PPI) network, we obtained network hub genes and validated the hub genes prognostic value and expression levels of protein.</p><p><strong>Results: </strong>Through analysis of differential gene expression, from the GEO and TCGA databases 2,139 and 2,774 DEGs were obtained, respectively, 13 and 15 modules were screened from TCGA-LSCC and GSE127165 datasets by WGCNA, respectively. The most significant positive and negative correlation modules in the WGCNA and DEG lists were overlapped, and overall 36 co-expressed overlapping genes were retrieved. Through enrichment analysis of GO and KEGG, it was found that the gene functions were highly concentrated in cell junction assembly, basement membrane, extracellular matrix (ECM) structural constituent etc., and the pathways were mainly concentrated in ECM receptor interaction, focal adhesion, small cell lung cancer, and toxoplasmosis. Through analysis of PPI network analysis, 10 network hub genes (<i>SNAI2, ITGA6, LAMB3, LAMC2, CAV1, COL7A1, GJA1, EHF, OAT</i>, and <i>GPT</i>) were obtained. Finally, survival analysis and protein expression validation of these genes confirmed that low <i>OAT</i> expression and high <i>CAV1</i> expression remarkably influenced the survival of patient's prognosis with LSCC.</p><p><strong>Conclusions: </strong>We recognized the hub genes and key modules nearly associated to LSCC and these genes were validated by survival analysis and the database of Human Protein Atlas (HPA), which is of high importance for unveiling the pathogenesis of LSCC and probing for new precise biological marker and potential therapeutic targets.</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/PMC11319952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983286","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":"Integrating network pharmacology and computational biology to propose Yiqi Sanjie formula's mechanisms in treating NSCLC: molecular docking, ADMET, and molecular dynamics simulation.","authors":"Yunzhen Wang, Guijuan He, Mire Zloh, Tao Shen, Zhengfu He","doi":"10.21037/tcr-24-972","DOIUrl":"10.21037/tcr-24-972","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths globally. Current treatments often do not fully meet efficacy and quality of life expectations. Traditional Chinese medicine (TCM), particularly the Yiqi Sanjie formula, shows promise but lacks clear mechanistic understanding. This study addresses this gap by investigating the therapeutic effects and underlying mechanisms of Yiqi Sanjie formula in NSCLC.</p><p><strong>Methods: </strong>We utilized network pharmacology to identify potential NSCLC drug targets of the Yiqi Sanjie formula via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Compounds with favorable oral bioavailability and drug-likeness scores were selected. Molecular docking was conducted using AutoDock Vina with structural data from the Protein Data Bank and PubChem. Molecular dynamics (MD) simulations were performed with Desmond Molecular Dynamics System, analyzing interactions up to 500 nanoseconds using the OPLS4 force field. ADMET predictions were executed using SwissADME and ADMETlab 2.0, assessing pharmacokinetic properties.</p><p><strong>Results: </strong>Using network pharmacology tools, we performed Search Tool for the Retrieval of Interaction Genes/Proteins (STRING) analysis for protein-protein interaction, Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway enrichment, and gene ontology (GO) for functional enrichment, identifying crucial signaling pathways and biological processes influenced by the hit compounds bifendate, xambioona, and hederagenin. STRING analysis indicated substantial connectivity among the targets, suggesting significant interactions within the cell cycle regulation and growth factor signaling pathways as outlined in our KEGG results. The GO analysis highlighted their involvement in critical biological processes such as cell cycle control, apoptosis, and drug response. Molecular docking simulations quantified the binding efficiencies of the identified compounds with their targets-CCND1, CDK4, and EGFR-selected based on high docking scores that suggest strong potential interactions crucial for NSCLC inhibition. Subsequent MD simulations validated the stability of these complexes, supporting their potential as therapeutic interventions. Additionally, the novel identification of ADH1B as a target underscores its prospective significance in NSCLC therapy, further expanded by our comprehensive bioinformatics approach.</p><p><strong>Conclusions: </strong>Our research demonstrates the potential of integrating network pharmacology and computational biology to elucidate the mechanisms of the Yiqi Sanjie formula in NSCLC treatment. The identified compounds could lead to novel targeted therapies, especially for patients with overexpressed targets. The discovery of ADH1B as a therapeutic target adds a new dimension to NSCLC treatment strategies. Further studies, both <i>in vitro</i> and <i>in vivo</i>, are needed to co","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/PMC11319956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983288","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":"Machine learning-based integration of CD8 T cell-related gene signatures for comprehensive prognostic assessment in lung adenocarcinoma.","authors":"Jing Yong, Dongdong Wang, Huiming Yu","doi":"10.21037/tcr-23-2332","DOIUrl":"10.21037/tcr-23-2332","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) stands as the most prevalent histological subtype of lung cancer, exhibiting heterogeneity in outcomes and diverse responses to therapy. CD8 T cells are consistently present throughout all stages of tumor development and play a pivotal role within the tumor microenvironment (TME). Our objective was to investigate the expression profiles of CD8 T cell marker genes, establish a prognostic risk model based on these genes in LUAD, and explore its relationship with immunotherapy response.</p><p><strong>Methods: </strong>By leveraging the expression data and clinical records from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts, we identified 23 consensus prognostic genes. Employing ten machine-learning algorithms, we generated 101 combinations, ultimately selecting the optimal algorithm to construct an artificial intelligence-derived prognostic signature named riskScore. This selection was based on the average concordance index (C-index) across three testing cohorts.</p><p><strong>Results: </strong>RiskScore emerged as an independent risk factor for overall survival (OS), progression-free interval (PFI), disease-free interval (DFI), and disease-specific survival (DSS) in LUAD. Notably, riskScore exhibited notably superior predictive accuracy compared to traditional clinical variables. Furthermore, we observed a positive correlation between the high-risk riskScore group and tumor-promoting biological functions, lower tumor mutational burden (TMB), lower neoantigen (NEO) load, and lower microsatellite instability (MSI) scores, as well as reduced immune cell infiltration and an increased probability of immune evasion within the TME. Of significance, the immunophenoscore (IPS) score displayed significant differences among risk subgroups, and riskScore effectively stratified patients in the IMvigor210 and GSE135222 immunotherapy cohort based on their survival outcomes. Additionally, we identified potential drugs that could target specific risk subgroups.</p><p><strong>Conclusions: </strong>In summary, riskScore demonstrates its potential as a robust and promising tool for guiding clinical management and tailoring individualized treatments for LUAD patients.</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/PMC11319961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983290","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":"Monocytes-to-lymphocytes ratio increases the prognostic value of circulating tumor cells in non-small cell lung cancer: a prospective study.","authors":"Yun Huangfu, Fangfang Chang, Fengjuan Zhang, Yanru Jiao, Lei Han","doi":"10.21037/tcr-24-10","DOIUrl":"10.21037/tcr-24-10","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor cells (CTCs) has shown important prognostic value in non-small cell lung cancer (NSCLC). However, the present low sensitivity of CTC capture technology restricts their clinical application. This study aims to explore the feasibility of combining the peripheral blood cell (PBC)-derived inflammation-based score with CTCs to increase the prognostic value of CTCs in NSCLC.</p><p><strong>Methods: </strong>Sixty volunteers diagnosed with NSCLC were recruited. CTC count and six inflammation-based scores were examined and the association with progression-free survival (PFS) and overall survival (OS) was explored. The changes in the CTC counts before and after the immunotherapy were observed.</p><p><strong>Results: </strong>Multivariate analysis showed that CTCs >7 [hazard ratio (HR) =9.07; 95% confidence interval (CI): 3.68-22.37, P<0.001] and monocytes-to-lymphocytes ratio (MLR) > 0.2 (HR =3.07; 95% CI: 1.21-7.84; P=0.01) were associated with shorter OS and PFS in patients with NSCLC. Patients with CTCs >7 and MLR >0.2 had 12.30 times increased risk of death (P<0.001) and 6.10 times increased risk of disease progression (P=0.002) compared with those with CTCs ≤7 and MLR ≤0.2. Decreased CTC counts after immunotherapy were closely related to disease control (r=0.535, P=0.01).</p><p><strong>Conclusions: </strong>CTCs and MLR are both independent risk factors for prognosis in patients with NSCLC. The combination of CTCs with MLR significantly increased the prognostic value of CTCs, which would contribute to stratification of NSCLC patients and providing precise treatment. Dynamic monitoring of CTCs efficiently shows the immunotherapy response in NSCLC.</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/PMC11319958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983292","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":"Correlation between initial alkaline phosphatase levels and overall survival in newly diagnosed multiple myeloma patients.","authors":"Jie Tan, Jun-Peng Liu, Xing-Chen Yao, Zi-Yu Xu, Yue Wu, Xiang-Jun Shi, Ming Shi, Meng Li, Xin-Ru Du","doi":"10.21037/tcr-24-330","DOIUrl":"10.21037/tcr-24-330","url":null,"abstract":"<p><strong>Background: </strong>Alkaline phosphatase (ALP) reflects changes in the condition of multiple myeloma (MM) patients to some extent. However, the relationship of ALP in MM remains uncertain. Our study aimed to determine the association between initial ALP levels and overall survival in newly diagnosed MM patients.</p><p><strong>Methods: </strong>Clinical data from 202 newly diagnosed MM patients at Beijing Chaoyang Hospital between 2012 and 2016 were collected. Baseline characteristics, disease progression staging, serum markers, and patient survival data were recorded. The cut-off value for ALP was calculated based on patient survival data, and patients were divided into groups. Differences in patients' 3- and 5-year survival rates, liver function, bone disease and other indicators among different groups were compared. Independent risk factors influencing newly diagnosed MM patients were identified using COX regression analysis.</p><p><strong>Results: </strong>Patients were categorized into three groups based on ALP cut-off points: Group 1 (ALP <70 U/L), Group 2 (ALP 70 to <120 U/L), and Group 3 (ALP ≥120 U/L). Significant differences were observed in lactate dehydrogenase, serum calcium, white blood cell count, hemoglobin, and liver function indicators (including alanine aminotransferase, aspartate aminotransferase, albumin, and γ-glutamyl transferase) among different ALP groups (P<0.05). ALP levels varied significantly among patients with different bone disease grades (P<0.05). Median survival times for Groups 1, 2, and 3 were 25, 52, and 31 months, respectively. Group 2 exhibited significantly higher 3-year survival compared to the other two groups (P=0.006), while no significant difference was observed in 5-year survival among the three groups (P=0.51). Age, International Staging System staging, aspartate aminotransferase, β2-microglobulin, ALP grading, and severe bone disease were identified as independent factors influencing survival in newly diagnosed patients (P<0.05).</p><p><strong>Conclusions: </strong>ALP levels are correlated with the prognosis of MM patients, and an ALP range of 70 to <120 U/L reflects a better survival expectation.</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/PMC11319959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983325","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":"Expression profiles of serum transfer RNA-derived fragments and their potential roles in non-small cell lung cancer.","authors":"Yulan Song, Jipeng Li","doi":"10.21037/tcr-23-2364","DOIUrl":"10.21037/tcr-23-2364","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis can significantly improve the prognosis of patients. Transfer RNA (tRNA)-derived fragments (tRFs) have been found to have a crucial function in the pathophysiology of cancers. However, the role of tRFs/tRNA halves (tiRNAs) in NSCLC is yet unknown. The present study aimed to investigate unique expression profiles of tRFs/tiRNAs in NSCLC and search novel biomarkers for the diagnosis.</p><p><strong>Methods: </strong>RNA-sequencing was utilized for determining differently expressed tRFs/tiRNAs in serum in NSCLC and healthy controls. Stem-loop quantitative polymerase chain reaction (PCR) was used to confirm the selected tRFs/tiRNAs expressions. Their possible roles in NSCLC were predicted using bioinformatic research.</p><p><strong>Results: </strong>Eleven up-regulated tRFs/tiRNAs and 18 down-regulated tRFs/tiRNAs were determined. Levels of tRF-31-87R8WP9N1EWJ0 and tRF-31-79MP9P9NH57SD were significantly higher in NSCLC serum samples than those of healthy controls; the receiver operating characteristic (ROC) curve suggested that they could serve as new diagnostic biomarkers. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis hinted that tRF-31-87R8WP9N1EWJ0 and tRF-31-79MP9P9NH57SD might influence the development and manifestation of NSCLC.</p><p><strong>Conclusions: </strong>In NSCLC patients' serum, the tRFs/tiRNAs were abnormally regulated and that tRF-31-87R8WP9N1EWJ0 and tRF-31-79MP9P9NH57SD might be the potential biological markers for NSCLC.</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/PMC11322679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983360","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 and validation of endoplasmic reticulum stress-related genes that enhance immunotherapy in colon cancer.","authors":"Baolin Wang, Jun Yang, Jiexin Wu, Xiaoming Hu, Jun Zhu, Jiang Fang, Bo Han, Bo Zhou","doi":"10.21037/tcr-23-2227","DOIUrl":"10.21037/tcr-23-2227","url":null,"abstract":"<p><strong>Background: </strong>Endoplasmic reticulum stress (ERS)-related genes are related to tumor growth, metastasis, and immunotherapy response. In this paper, we tried to identify ERS-related genes related to immunotherapy in colon cancer.</p><p><strong>Methods: </strong>ERS-related genes were downloaded from the Molecular Signatures Database (MSigDB) and GeneCards websites. Normal and tumor samples of the colon were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), and Gene Expression Omnibus (GEO) databases. A risk model based on gene coefficients was constructed by using the least absolute shrinkage and selection operator (LASSO) regression. The inherent biological process differences between risk groups were explored by Gene Ontology (GO) and gene set enrichment analysis (GSEA). ESTIMATE and single-sample GSEA (ssGSEA) algorithms were used to analyze the correlation between tumor microenvironment (TME) and immune checkpoint and risk score. The semi-inhibitory concentration (IC₅₀) values of chemotherapeutic drugs between risk groups were calculated to evaluate the sensitivity of immunotherapy.</p><p><strong>Results: </strong>The pathway analysis showed that the ERS risk model was relevant to biosynthesis and metabolism. Consistent clustering based on the ERS-related differentially expressed genes (DEGs) demonstrated that the samples divided into three clusters had significant clinicopathological differences. A risk model consisting of six ERS-related genes was established. The model was verified on GSE39582 and GSE17536 testing datasets. The results showed that ERS risk model was significantly related to TME and immune checkpoint, and these genes enhanced the immunotherapy ability of colon cancer.</p><p><strong>Conclusions: </strong>We established a risk model with ERS-related genes (<i>PMM2</i>, <i>STC2</i>, <i>EIF2AK1</i>, <i>HSPA1A</i>, <i>SLC8A1</i>, <i>KCNQ1</i>), which enhance the sensitivity of immunotherapy for colon cancer. These may provide a new perspective for the treatment of colon 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/PMC11319978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983361","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 retrospective study of anlotinib in patients with persistent, recurrent or metastatic cervical and endometrial cancer.","authors":"Lingli Xin, Mei Ye, Yuan Gao, Qi Xiong, Qingxiang Hou","doi":"10.21037/tcr-24-272","DOIUrl":"10.21037/tcr-24-272","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of persistent, recurrent or metastatic cervical and endometrial cancer is poor. Anlotinib is a novel multitarget tyrosine kinase inhibitor (TKI). The efficacy and safety of anlotinib in patients with cervical and endometrial cancer need to be evaluated.</p><p><strong>Methods: </strong>We retrospectively analyzed the efficacy and safety of anlotinib in patients with persistent, recurrent or metastatic cervical and endometrial cancers between March 2020 and June 2023. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed.</p><p><strong>Results: </strong>The overall ORR and DCR were 24.14% and 55.17% respectively. The ORR and DCR in patients with cervical cancer were 25.00% and 56.25%; the ORR and DCR in patients with endometrial cancer were 23.08% and 53.85%. The patients received anlotinib plus immunotherapy had significantly higher rate of clinical benefit than those receiving anlotinnb alone (P=0.04). The DCR was significantly higher in patients receiving anlotinib combined with immunotherapy (DCR: 75.00% <i>vs.</i> 30.76%) than those without immunotherapy. The overall median PFS and OS were 12.2 months [95% confidence interval (CI): 6.6-17.8] and 22.3 months (95% CI: 20.9-23.7), respectively. The patients receiving anlotinib plus immunotherapy had significantly longer OS than those without immunotherapy [not reached <i>vs.</i> 12.5 months; hazard ratio (HR): 0.32 (95% CI: 0.1-0.99); P=0.04]. The most common AEs was fatigue (41.4%).</p><p><strong>Conclusions: </strong>Anlotinib might be a promising agent for persistent, recurrent or metastatic cervical and endometrial cancers with good tolerability. Moreover, anlotinib combined with immunotherapy showed synergistic antitumor effect.</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/PMC11319963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983278","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}