{"title":"Prognostic significance of connective tissue growth factor expression in stromal cells in patients with diffuse‑type gastric cancer.","authors":"Yuichiro Miki, Mami Yoshii, Ryoko Miyauchi, Hiroaki Kasashima, Tatsunari Fukuoka, Tatsuro Tamura, Masatsune Shibutani, Takahiro Toyokawa, Shigeru Lee, Masakazu Yashiro, Kiyoshi Maeda","doi":"10.3892/ol.2024.14374","DOIUrl":"https://doi.org/10.3892/ol.2024.14374","url":null,"abstract":"Connective tissue growth factor (CTGF) is a target gene of the Hippo signaling pathway. Its differential role in the histological types of gastric cancer (GC) remains unknown; therefore, the present study aimed to confirm the clinical significance of CTGF expression in cancer and stromal cells in patients with GC depending on the histological type. The present study enrolled 589 patients with GC. Immunohistochemistry was used to analyze CTGF expression in cancer and stromal cells. CTGF mRNA expression data and the corresponding clinical information of GC samples were collected from The Cancer Genome Atlas (TCGA) database. Subsequently, the associations between CTGF expression and several clinicopathological factors were investigated. In the present study, CTGF expression was mainly observed in the cytoplasm of cancer and stromal cells. CTGF expression in stromal cells was significantly associated with CTGF expression in cancer cells (P<0.001). CTGF positivity in stromal cells was also significantly associated with intestinal type, non-scirrhous type, tumor depth (T1-2), lymph node metastasis (negative), lymphatic invasion (negative) and tumor size (<5 cm). Low CTGF expression in stromal cells was independently associated with worse overall survival (OS). Furthermore, the OS of patients with low CTGF expression in stromal cells, especially in patients with diffuse-type GC, was significantly worse than patients with high CTGF expression (P=0.022). This trend was similar to that revealed by TCGA data analysis. In conclusion, low CTGF expression was associated with a significantly worse OS in patients with diffuse-type GC. These data indicated that CTGF, and its control by the Hippo pathway, may be considered potential treatment targets in diffuse-type GC.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"15 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tae Jeong Oh, Seunghyun Jang, Su Ji Kim, Min A Woo, Ji Woong Son, In Beom Jeong, Min Hyeok Lee, Sungwhan An
{"title":"Identification and validation of PCDHGA12 and PRRX1 methylation for detecting lung cancer in bronchial washing sample.","authors":"Tae Jeong Oh, Seunghyun Jang, Su Ji Kim, Min A Woo, Ji Woong Son, In Beom Jeong, Min Hyeok Lee, Sungwhan An","doi":"10.3892/ol.2024.14379","DOIUrl":"https://doi.org/10.3892/ol.2024.14379","url":null,"abstract":"Bronchoscopy is a frequently used initial diagnostic procedure for patients with suspected lung cancer (LC). Cytological examinations of bronchial washing (BW) samples obtained during bronchoscopy often yield inconclusive results regarding LC diagnosis. The present study aimed to identify molecular biomarkers as a non-invasive method for LC diagnosis. Aberrant DNA methylation is used as a useful biomarker for LC. Therefore, microarray-based methylation profiling analyses on 13 patient-matched tumor tissues at stages I-III vs. non-tumor tissues were performed, and a group of highly differentially methylated genes was identified. A subsequent analysis using bisulfite-pyrosequencing with additional tissues and cell lines revealed six methylated genes [ADAM metallopeptidase with thrombospondin type 1 motif 20, forkhead box C2 (mesenchyme forkhead 1), NK2 transcription factor related, locus 5 (<i>Drosophila</i>), oligodendrocyte transcription factor 3, protocadherin γ subfamily A 12 (<i>PCDHGA12</i>) and paired related homeobox 1 (<i>PRRX1</i>)] associated with LC. Next, a highly sensitive and accurate detection method, linear target enrichment-quantitative methylation-specific PCR in a single closed tube, was applied for clinical validation using BW samples from patients with LC (n=68) and individuals with benign diseases (n=33). <i>PCDHGA12</i> and <i>PRRX1</i> methylation were identified as the best-performing biomarkers to detect LC. The two-marker combination showed a sensitivity of 82.4% and a specificity of 87.9%, with an area under the curve of 0.891. Notably, the sensitivity for small cell LC was 100%. The two-marker combination had a positive predictive value of 93.3% and a negative predictive value of 70.7%. The sensitivity was higher than that of cytology, which only had a sensitivity of 50%. The methylation status of the two-marker combination showed no association with sex, age or stage, but was associated with tumor location and histology. In conclusion, the present study showed that the regulatory regions of <i>PCDHGA12</i> and <i>PRRX1</i> are highly methylated in LC and can be used to detect LC in BW specimens as a diagnostic adjunct to cytology in clinical practice.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"1 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Longxun Zhou, Yuqun Shan, Jun Li, Min Li, Zhen Meng, Na Guo
{"title":"Early growth response 1 regulates dual‑specificity protein phosphatase 1 and inhibits cell migration and invasion of tongue squamous cell carcinoma.","authors":"Longxun Zhou, Yuqun Shan, Jun Li, Min Li, Zhen Meng, Na Guo","doi":"10.3892/ol.2024.14373","DOIUrl":"https://doi.org/10.3892/ol.2024.14373","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"71 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A fully validated LC‑MS/MS method for quantifying bevacizumab in plasma samples from patients with NSCLC and its implications in therapeutic drug monitoring.","authors":"Bo Li, Meng Yang, Xiaoxue Wang, Wenqian Chen, Hongkai Lu, Guan Wang, Liang Sun, Xiaoyang Liu, Xianbo Zuo, Pengmei Li, Lihong Liu, Xianglin Zhang","doi":"10.3892/ol.2024.14356","DOIUrl":"https://doi.org/10.3892/ol.2024.14356","url":null,"abstract":"Given the increasing use of bevacizumab in combinatorial drug therapy for a multitude of different cancer types, there is a need for therapeutic drug monitoring to analyze the possible correlation between drug trough concentration, and therapeutic effect and adverse reactions. An ultra-performance liquid chromatography tandem-mass spectrometry method was then developed and validated to determine bevacizumab levels in human plasma samples. Chromatographic separation was achieved on a Shimadzu InertSustainBio C18 HP column, whereas subsequent mass spectrometric analysis was performed using a Shimadzu 8050CL triple quadrupole mass spectrometer equipped with an electro-spray ionization source in the positive ion mode. In total, three multiple reaction monitoring transitions of each of the surrogate peptides were chosen with 'FTFSLDTSK' applied as the quantification peptide whereas 'VLIYFTSSLHSGVPSR' and 'STAYLQMNSLR' were designated as the verification peptides using the Skyline software. This analytical method was then fully validated, with specificity, linearity, lower limit of quantitation, accuracy, precision, stability, matrix effect and recovery calculated. The linearity of this method was developed to be within the concentration range 5-400 µg/ml for bevacizumab in human plasma. Subsequently, eight patients with non-small cell lung cancer (NSCLC) were recruited and injected with bevacizumab over three periods of treatment to analyze their steady-state trough concentration and differences. To conclude, the results of the present study suggest that bevacizumab can be monitored in a therapeutic setting in patients with NSCLC.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"44 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology LettersPub Date : 2024-02-29eCollection Date: 2024-04-01DOI: 10.3892/ol.2024.14317
Gaojie Xin, Naicheng Song, Ke Jiang
{"title":"Esophageal squamous cell carcinoma transformed into neuroendocrine carcinoma after neoadjuvant immunochemotherapy: A case report.","authors":"Gaojie Xin, Naicheng Song, Ke Jiang","doi":"10.3892/ol.2024.14317","DOIUrl":"10.3892/ol.2024.14317","url":null,"abstract":"<p><p>Immunotherapy provides durable responses for locally advanced esophageal carcinoma clinical therapy in numerous patients. However, the mechanisms of resistance to immunotherapy have not been elucidated. The phenomenon of the histological transformation of non-small cell lung cancer to small cell lung cancer resulting in resistance to immune checkpoint inhibitors (ICIs) has been reported. It remains unclear whether ICIs or chemotherapy could cause a similar transformation from esophageal squamous cell carcinoma (ESCC) to esophageal neuroendocrine carcinoma (ENEC). The present study report the case of a patient initially diagnosed with stage II ESCC who underwent radical surgery after three cycles of neoadjuvant therapy with cisplatin, albumin bound paclitaxel and ICIs. Immunohistochemical staining confirmed the absence of the SCC component and the presence of the NEC component, with negativity for CK5/6 and tumor protein p40, but positive expression of tumor protein p53, pan-cytokeratin, synaptophysin and CD56. The patient was followed up for 5 months with no treatment or postoperative complications. In conclusion, histological transformation to ENEC is a potential mechanism of acquired resistance to ICIs in ESCC. Prospective larger studies are warranted to further characterize ESCC-to-NEC transformation on use of ICIs.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"27 4","pages":"184"},"PeriodicalIF":2.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10928968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111129","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 cancer‑associated fibroblasts: A novel subgroup in the cervical cancer microenvironment that exhibits tumor‑promoting roles and prognosis biomarker functions.","authors":"Yuehan Wang, Mingxia Xu, Yeli Yao, Ying Li, Songfa Zhang, Yunfeng Fu, Xinyu Wang","doi":"10.3892/ol.2024.14300","DOIUrl":"10.3892/ol.2024.14300","url":null,"abstract":"<p><p>Tumor invasion and metastasis are the processes that primarily cause adverse outcomes in patients with cervical cancer. Cancer-associated fibroblasts (CAFs), which participate in cancer progression and metastasis, are novel targets for the treatment of tumors. The present study aimed to assess the heterogeneity of CAFs in the cervical cancer microenvironment through single-cell RNA sequencing. After collecting five cervical cancer samples and obtaining the CAF-associated gene sets, the CAFs in the cervical cancer microenvironment were divided into myofibroblastic CAFs and extracellular (ec)CAFs. The ecCAFs appeared with more robust pro-tumorigenic effects than myCAFs according to enrichment analysis. Subsequently, through combining the ecCAF hub genes and bulk gene expression data for cervical cancer obtained from The Cancer Genome Atlas and Gene Ontology databases, univariate Cox regression and least absolute shrinkage and selection operator analyses were performed to establish a CAF-associated risk signature for patients with cancer. The established risk signature demonstrated a stable and strong prognostic capability in both the training and validation cohorts. Subsequently, the association between the risk signature and clinical data was evaluated, and a nomogram to facilitate clinical application was established. The risk score was demonstrated to be associated with both the tumor immune microenvironment and the therapeutic responses. Moreover, the signature also has predictive value for the prognosis of head and neck squamous cell carcinoma, and bladder urothelial carcinoma, which were also associated with human papillomavirus infection. In conclusion, the present study assessed the heterogeneity of CAFs in the cervical cancer microenvironment, and a subgroup of CAFs that may be closely associated with tumor progression was defined. Moreover, a signature based on the hub genes of ecCAFs was shown to have biomarker functionality in terms of predicting survival rates, and therefore this CAF subgroup may become a therapeutic target for cervical cancer in the future.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"27 4","pages":"167"},"PeriodicalIF":2.5,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050016","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":"Efficacy of nab‑paclitaxel vs. Gemcitabine in combination with S‑1 for advanced pancreatic cancer: A multicenter phase II randomized trial.","authors":"Xi Guo, Wenhui Lou, Yaolin Xu, Rongyuan Zhuang, Lie Yao, Junwei Wu, Deliang Fu, Jun Zhang, Jing Liu, Yefei Rong, Dayong Jin, Wenchuan Wu, Xuefeng Xu, Yuan Ji, Lili Wu, Minzhi Lv, Xiuzhong Yao, Xiaowei Liu, Dansong Wang, Tiantao Kuang, Liang Liu, Wenquan Wang, Tianshu Liu, Yuhong Zhou","doi":"10.3892/ol.2024.14293","DOIUrl":"10.3892/ol.2024.14293","url":null,"abstract":"<p><p>Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-naïve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m<sup>2</sup> nab-paclitaxel, days 1 and 8; 80-120 mg S-1, days 1-14) or GS (1,000 mg/m<sup>2</sup> gemcitabine, days 1 and 8; 80-120 mg S-1, days 1-14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31-13.24]. The median PFS was 7.16 months (95% CI, 5.19-12.32) for patients treated with AS and 6.41 months (95% CI, 3.72-8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51-1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had <i>KRAS</i> gene mutations and high C-reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with <i>KRAS</i> gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"27 4","pages":"161"},"PeriodicalIF":2.5,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050015","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":"Implication of PD‑L1 polymorphisms rs2297136 on clinical outcomes of patients with advanced NSCLC who received PD‑1 blockades: A retrospective exploratory study.","authors":"Qiang Gong, Hai-Ling Qie, Shao-Yong Dong, Hong-Tao Jiang","doi":"10.3892/ol.2024.14277","DOIUrl":"https://doi.org/10.3892/ol.2024.14277","url":null,"abstract":"Clinically, programmed death-1 (PD-1) blockades have demonstrated promising therapeutic outcomes for patients with advanced non-small cell lung cancer (NSCLC). The present study aimed to examine the impact of programmed death-ligand 1 (PD-L1) polymorphism on clinical outcomes of patients with advanced NSCLC who were treated with PD-1 blockades therapy. The present study was designed as a retrospective analysis, where a consecutive screening of 89 patients with advanced NSCLC who received PD-1 blockades monotherapy were screened. Biological specimens were collected to determine the presence of polymorphism and PD-L1 mRNA expression through genotyping. The analysis focused on examining the relationship between the genotype status of PD-L1 polymorphism and clinical outcomes. Among the 89 patients with advanced NSCLC, the use of PD-1 blockades monotherapy resulted in objective response rate (ORR) of 22.5%, a median progression-free survival (PFS) of 3.4 months [95% Confidence Interval (CI): 1.80-5.00) and a median overall survival (OS) of 11.3 months (95% CI: 7.93-14.67). The analysis of polymorphism indicated that only rs2297136 had clinical significance. Among the 89 patients with NSCLC, the prevalence of rs2297136 was as follows: A total of 58 cases (65.2%) had the AA genotype, 28 cases (31.5%) had the AG genotype and 3 cases (3.4%) had the GG genotype. This resulted in a minor allele frequency of 0.19, which was in consistent with Hardy-Weinberg Equilibrium (P=0.865). The correlation analysis between genotype status of rs2297136 and clinical outcomes indicated that patients with the AA genotype had an ORR of 19.0%, while those with the AG/GG genotype had an ORR of 29.0% (P=0.278). Additionally, the median PFS for the AA genotype was 2.95 months, compared with 5.30 months for the AG/GG genotype (P=0.038). Accordingly, median OS of the AA and AG/GG genotypes was 8.8 and 18.4 months, respectively (P=0.011). The mRNA expression of PD-L1 was significantly higher in patients with AG/GG genotype compared with those with AA genotype (P<0.001). In clinical practice, PD-1 blockades demonstrated promising effectiveness in treating patients with advanced NSCLC. The presence of the rs2297136 variant in PD-L1 gene could potentially be used as a biomarker to predict the clinical outcomes of PD-1 blockades.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology LettersPub Date : 2024-01-11eCollection Date: 2024-03-01DOI: 10.3892/ol.2024.14227
Sang Eun Ha, Anjugam Paramanantham, Hun Hwan Kim, Pritam Bhagwan Bhosale, Min Yeong Park, Abuyaseer Abusaliya, Jeong Doo Heo, Won Sup Lee, Gon Sup Kim
{"title":"Comprehensive transcriptomic profiling of liver cancer identifies that histone and PTEN are major regulators of SCU‑induced antitumor activity.","authors":"Sang Eun Ha, Anjugam Paramanantham, Hun Hwan Kim, Pritam Bhagwan Bhosale, Min Yeong Park, Abuyaseer Abusaliya, Jeong Doo Heo, Won Sup Lee, Gon Sup Kim","doi":"10.3892/ol.2024.14227","DOIUrl":"10.3892/ol.2024.14227","url":null,"abstract":"<p><p>Worldwide, liver cancer is the most frequent fatal malignancy. Liver cancer prognosis is poor because patients frequently receive advanced-stage diagnoses. The current study aimed to establish the potential pharmacological targets and the biological networks of scutellarein (SCU) in liver cancer, a natural product known to have low toxicity and side effects. To identify the differentially expressed genes between SCU-treated and SCU-untreated HepG2 cells, RNA sequencing (RNA-seq) was carried out. A total of 463 genes were revealed to have differential expression, of which 288 were upregulated and 175 were downregulated in the group that had received SCU treatment compared with a control group. Gene Ontology (GO) enrichment analysis of associated biological process terms revealed they were mostly involved in the regulation of protein heterodimerization activity and nucleosomes. Interaction of protein-protein network analysis using Search Tool for the Retrieval of Interacting Genes/Proteins resulted in two crucial interacting hub targets; namely, histone H1-4 and protein tyrosine phosphatase receptor type C. Additionally, the crucial targets were validated using western blotting. Overall, the present study demonstrated that the use of RNA-seq data, with bioinformatics tools, can provide a valuable resource to identify the pharmacological targets that could have important biological roles in liver cancer.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"27 3","pages":"94"},"PeriodicalIF":2.5,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576105","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}