Journal of Cancer最新文献

{"title":"Integrative Analysis and Validation of a Cancer-associated Fibroblasts Senescence-related Signature for Risk Stratification and Therapeutic Prediction in Esophageal Squamous Cell Carcinoma.","authors":"Han Zhang, Kunqiao Hong, Qi Song, Beibei Zhu, Gang Wu, Baoping Yu","doi":"10.7150/jca.100430","DOIUrl":"10.7150/jca.100430","url":null,"abstract":"<p><p>Cellular senescence is closely associated with cancer development and progression. There is ample evidence that tumor stromal cells, especially cancer-associated fibroblasts (CAFs) undergo senescence in response to various stimuli. However, the possible biological roles and prognostic significance of senescent CAFs in esophageal squamous cell carcinoma (ESCC) remain unexplored. In this study, we found that CAFs exhibited a significantly higher level of cellular senescence than other cell clusters at the single-cell level. Then, we constructed a CAFs senescence-associated risk model with 7 genes (<i>GEM</i>, <i>SLC2A6</i>, <i>CXCL14</i>, <i>STX11</i>, <i>EFHD2</i>, <i>PTX3</i>, and <i>HCK</i>) through Cox regression and LASSO analysis. Kaplan-Meier survival analysis revealed that the risk model was significantly correlated with worse prognosis in training and validation cohorts. Subsequent analysis indicated that the risk model was an independent prognostic factor. In addition, the signature showed a distinct negative correlation with immune cell infiltration and immunotherapy responses. <i>In vitro</i> experiments showed remarkably higher mRNA and protein levels of prognosis-related genes (<i>STX11</i> and <i>EFHD2</i>) in senescent CAFs than control group, consistent with the bioinformatics analysis results. Moreover, senescent CAFs significantly promoted ESCC cell proliferation and migration as shown by CCK-8 and scratch assays. In conclusion, our study identified a novel CAFs senescence-based classifier that may help predict prognosis of ESCC, and a thorough characterization of the signature could also be helpful in evaluating the response of ESCC to anti-tumor therapies and provide meaningful clinical options for cancer treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daphnoretin inhibits glioblastoma cell proliferation and metastasis via PI3K/AKT signaling pathway inactivation.","authors":"Jiaming Lei, Hong Zhou, Shijiao Cheng, Wenwen Yu, Meiting Yang, Li Lin","doi":"10.7150/jca.98915","DOIUrl":"10.7150/jca.98915","url":null,"abstract":"<p><p>Glioblastoma (GBM) was the most malignant intracranial tumor with high mortality rates and invariably poor prognosis due to its limited clinical treatments. The urgent need to develop new therapeutic drugs for GBM treatment is evident. As a coumarin derivative, daphnoretin's favorable pharmacological activities have been widely documented. However, the potential inhibitory effects of daphnoretin on GBM have not been explored. In this study, we aimed to investigate the effects of daphnoretin on GBM and elucidate its anti-GBM mechanisms for the first time. It was observed that daphnoretin inhibited GBM cell proliferation, migration, and invasion in vitro and suppressed tumor growth without significant drug toxicity in GBM xenograft tumor models <i>in vivo</i>. Mechanistically, daphnoretin was predicted to target the PI3K/AKT signaling pathway through network pharmacology and molecular docking analysis. Subsequently, it was further verified by Biacore assay for surface plasmon resonance (SPR) experiments. Experimentally, daphnoretin induced apoptosis in GBM cells via the PI3K/AKT signaling pathway. Moreover, the effects of daphnoretin on GBM cells could be reversed by the AKT activator SC79. These results suggest that daphnoretin holds potential as a therapeutic drug against GBM and provides new insights into GBM treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High expression of ABL2 promotes gastric cancer cells migration, invasion and proliferation via the TGF-β and YAP signaling pathways.","authors":"Yun Liu, Tao Jin, Ruiyun Chen, Renjie Miao, Yong Zhou, Shihe Shao","doi":"10.7150/jca.99307","DOIUrl":"10.7150/jca.99307","url":null,"abstract":"<p><p><b>Background:</b> The Abelson-Related Gene (ABL2) is expressed in various malignancies. However, its role in gastric cancer (GC) regarding tumor proliferation, metastasis, and invasion remains unclear. <b>Methods:</b> ABL2 expression in clinical specimens was assessed using quantitative real-time fluorescence PCR (qRT-PCR). Western blotting and immunofluorescence assay determined protein levels. Additionally, Transwell migration and invasion, cell counting kit-8 (CCK-8) and colony-formation assays analyzed the effect of ABL2 on GC cells. Protein levels related to GC cells were assessed through Western blotting. The effects of si-ABL2 combined with GA-017 that activated YAP on cell migration, invasion and proliferation were investigated. <b>Results:</b> ABL2 expression was upregulated in human GC tissues compared to paracancer tissues, and it was positively related to tumor node metastasis classification (TNM) stage. Furthermore, high ABL2 levels promoted the proliferation, metastasis, and invasion capacity in GC cells. Elevated ABL2 expression enhanced the expression of MMP2, MMP9, and PCNA while decreasing TIMP1 and TIMP2 expression. It also increased the p-SMAD2/3 expression and YAP expression, decreased the expression of p-YAP in GC cells. Furthermore, GA-017 increased ABL2 expression in MGC-803 cells and counteracted the effects of si-ABL2 on cell migration, invasion and proliferation. <b>Conclusion:</b> These findings indicated that heightened ABL2 expression could activate TGF-β/SMAD2/3 and YAP signaling pathway, promoting epithelial mesenchymal transformation (EMT), and enhancing multiplication, metastasis, and invasion in GC cells.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-dimensional Speckle Tracking Imaging in Cardiotoxicity Caused by Treatment of Breast Carcinoma with Anthracyclines.","authors":"Wenjuan Song, Xuejuan Ma, Yue Sun, Liping Liu, Ying Gu, Yue Zhao, Yujia Ye, Yu Wang","doi":"10.7150/jca.98204","DOIUrl":"10.7150/jca.98204","url":null,"abstract":"<p><p><b>Objective:</b> This research was conducted to investigate the monitoring values of routine echocardiography (ECG) and two-dimensional speckle tracking imaging (2D-STI) in cardiotoxicity caused by the treatment of breast carcinoma with anthracyclines (ANTH). <b>Methods:</b> 100 patients with breast carcinoma were selected and enrolled into normal group (n=53 cases) and abnormal group (47 cases) according to whether ECG was abnormal. Routine ECG and 2D-STI were employed for the detection, ECG- and 2D-STI-related parameters were compared, receiver operating characteristic (ROC) curves were drawn, and the clinical application values of monitoring methods for two groups were assessed. <b>Results:</b> Before chemotherapy, no remarkable statistical difference was detected in routine ECG and 2D-STI parameters between normal and abnormal groups (<i>P</i>>0.05). After 6 cycles, E/V value of abnormal group was inferior to that of normal group ((0.93±0.16) vs (1.33±0.23). Besides, longitudinal peak strain (SRI) values of rear wall, front spacer, and rear spacer in abnormal group were inferior to those in normal group (<i>P</i><0.05). Routine ECG combined with 2D-STI had the best predictive effect followed by 2D-STI and routine ECG. <b>Conclusion:</b> To sum up, 2D-STI was a new method for assessing myocardial lesions and possessed significant early clinical monitoring values in cardiotoxicity caused by chemotherapy after the treatment of breast carcinoma with ANTH. It had higher clinical application values than routine ECG.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and Immunological Role of Cuproptosis-Related Gene MTF1 in Pan-Cancer.","authors":"Chao Zhang, Sifen Wang, Hailin Tang, Renchun Lai, Qiaoting Cai, Yaorong Su, Hao Wu, Yongwen Huang","doi":"10.7150/jca.98749","DOIUrl":"10.7150/jca.98749","url":null,"abstract":"<p><p>Metal regulatory transcription factor 1 (MTF1) has been reported to induce the expression of metallothionein and other genes involved in metal homeostasis. However, the role of MTF1 in pan-cancer and tumor immunity remains unclear. In this study, we conducted a series of bioinformatics analyses to investigate the clinical significance and potential functions of MTF1 across various types of cancer. By employing bioinformatics algorithms and immunofluorescence assays, we analyzed the associations between MTF1 and immune infiltration in the tumor microenvironment as well as the expression levels of immune-related molecules. Our findings revealed dysregulation of MTF1 in pan-cancer along with its correlation with certain clinicopathological features, suggesting its diagnostic and prognostic value for multiple cancer types. Furthermore, our immune-associated analyses and assays demonstrated strong correlations between MTF1 expression and plasmacytoid dendritic cells (pDC), central memory T cells (Tcm), as well as several immune biomarkers. Subsequent in vitro assays indicated that MTF1 reduced the sensitivity of cancer cells to cuproptosis. Overall, our study highlights that MTF1 may serve as a promising biomarker for prognosis assessment and a potential therapeutic target for more effective treatment strategies against various cancers.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SCAMP1 silencing inhibits proliferation by attenuating multiple pro-survival signaling pathways in gastric cancer.","authors":"Gang Ma, Yang Yang, Fenglin Cai, Bin Ke, Jingyu Deng","doi":"10.7150/jca.99610","DOIUrl":"10.7150/jca.99610","url":null,"abstract":"<p><p>Secretory carrier-associated membrane protein 1 (SCAMP1) is the most universally expressed member of the SCAMP family, and its ability to facilitate endocytosis was demonstrated approximately two decades ago. Nevertheless, its roles in cancer biology are largely unknown, although its expression is significantly increased in most cancer types. Herein, we examined the expression of SCAMP1 in gastric cancer (GC) tissues and found that it was aberrantly increased and positively correlated with tumor size and lymph node metastasis. More importantly, increased SCAMP1 expression was associated with poor prognosis in patients with GC. Functional experiments demonstrated that SCAMP1 knockdown markedly suppressed the proliferation of GC cells <i>in vitro</i> and <i>in vivo</i>. RNA sequencing assays demonstrated that SCAMP1 knockdown altered the expression profile of GC cells, and a significant portion of the altered genes were enriched in receptor tyrosine kinases and their related downstream signaling pathways. Immunoblotting confirmed that the Akt/MAPK/Stat signaling pathway was strongly attenuated in GC cells with SCAMP1 depletion. Taken together, these results demonstrated that SCAMP1 drives hyperproliferation in GC cells, thus suggesting that further investigation into the mechanisms and translational value of SCAMP1 in treating patients with GC is warranted.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A survival nomogram involving nutritional-inflammatory indicators for cervical cancer patients receiving adjuvant radiotherapy.","authors":"Shanshan Wang, Mengli Zhao, Zhongrong Gao, Xiaojing Yang, Yudong Wang, Keqin Hua, Jie Fu","doi":"10.7150/jca.100564","DOIUrl":"10.7150/jca.100564","url":null,"abstract":"<p><p><b>Objective:</b> The combined impact of nutritional and inflammatory status on survival of cervical cancer patients remained unclear. This study aimed to construct a survival nomogram involving both nutritional and inflammatory indicators and evaluate their potential correlation. <b>Methods:</b> This retrospective study included 325 cervical cancer patients who received adjuvant radiotherapy between September 2010 and September 2020. Baseline nutritional indicators such as body mass index (BMI), controlling nutritional status (CONUT) and serum albumin were assessed. Inflammatory indicators of platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), systemic immune inflammation index (SII) and system inflammation response index (SIRI) were evaluated respectively. The LASSO regression and Cox regression models were applied for variable selection and nomogram building. The predictive accuracy and superiority of prognostic model were assessed by area under curve (AUC), C-index, decision curve analysis (DCA), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). <b>Results:</b> Patients with high inflammatory indicators (PLR, NLR and SII) and poor nutritional status (CONUT scores > 2) suffered poorer prognosis compared to these with well nutritional status and lower inflammation levels. Our study unveiled a positive correlation between malnutrition and hyperinflammation. Even after accounting for baseline inflammatory level, malnutrition remained a significant risk factor for patients. Notably, the inflammatory level and nutritional status were further modulated by the clinical features of patients. Patients with poorer nutritional status exhibited higher levels of PLR, NLR, SII and SIRI, particularly for those in advanced clinical stages and with non-squamous cell carcinoma. In addition, our study found elevated levels of circulating basophil and serum carbohydrate antigen 125 (CA125) were associated with the poor prognosis. The prognostic nomogram which incorporated the nutritional-inflammatory indicators of PLR and CONUT showed a favorable performance with the AUC value of 0.76 at 5-year survival prediction. The DCA, IDI and NRI consistently demonstrated the favorable superiority of the model. Moreover, the nomogram-based risk stratification system could effectively classify patients into three mortality risks subgroups. <b>Conclusions:</b> Poorer nutritional and high inflammatory status collectively contributed to the poorer prognosis. The prognostic nomogram which incorporated nutritional-inflammatory indicators significantly improved the prediction of long-term outcomes of cervical cancer patients undergoing adjuvant radiotherapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the Efficacy and Safety of Axi-Cel and Tisa-Cel Based on Meta-Analysis.","authors":"Chengcheng Liao, Lin Zeng, Shengjuan Lu, Shaocu Zheng, Baoping Guo, Qing Ke, Mingyue Wang, Jie Sun, Chao Rong, Sha He, Dani Zhong, Mei Huang, Xiaohong Tan, Hong Cen","doi":"10.7150/jca.99427","DOIUrl":"10.7150/jca.99427","url":null,"abstract":"<p><p>This study aimed to analyze the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy for B-cell lymphoma using published literature data. Literature on CAR-T therapy for B-cell lymphoma was collected by searching common databases. The literature was screened, quality assessed, and data extracted according to the inclusion and exclusion criteria. We performed a quantitative meta-analysis of the efficacy and safety of combined literature data. If the data could not be combined, descriptive analysis was performed. The meta-analysis results indicated that compared with tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel) had higher objective response rate (ORR) and complete response rate, with odds ratio (OR) of 0.63 for both sides (95% confidence interval [CI], 0.50-0.79) and statistically significant differences. Partial response rate was lower with axi-cel than with tisa-cel, with an OR of 1.02 for tisa-cel versus axi-cel (95% CI, 0.75-1.40) and no statistically significant difference. Compared with tisa-cel, axi-cel had longer progression-free survival and overall survival, with risk ratios of 0.70 (95% CI, 0.62-0.80) and 0.71 (95% CI, 0.61-0.84) for axi-cel and tisa-cel, respectively. Compared with tisa-cel, axi-cel had higher incidence rates of cytokine release syndrome (CRS) and immune effector cell-related neurotoxicity syndrome (ICANS), with ORs of 3.84 (95% CI, 2.10-7.03) and 4.4 (95% CI, 2.81-6.91), respectively. CAR T-cell therapy is an effective treatment option for relapsed/refractory B-cell lymphoma. Axi-cel has better ORR and survival advantages compared with tisa-cel; however, axi-cel has higher incidence rates of CRS and ICANS compared with tisa-cel.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MLPH regulates EMT in pancreatic adenocarcinoma through the PI3K-AKT signaling pathway.","authors":"Mengda Wei, Xi Yang, Xiaoying Yang, Yanqing Huang, Zhenmin Yuan, Junjie Huang, Junren Wei, Lei Tian","doi":"10.7150/jca.94573","DOIUrl":"10.7150/jca.94573","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PAAD) is an extremely malignant tumor, and most patients develop postoperative metastases. Melanophilin (MLPH) is involved in the progression of various tumors, but its molecular mechanisms and role in pancreatic cancer progression are unknown. In this study, differential MLPH expression in cancer tissues and the adjacent tissues was evaluated using the Gene Expression Profiling Interaction Analysis 2 (GEPIA 2) and Human Protein Atlas (HPA) databases. The role of MLPH in PAAD proliferation, invasion, and migration <i>in vitro</i> was explored <i>via</i> clone formation, Cell Counting Kit-8 assay, Transwell assay, and western blot. The <i>in vivo</i> validation of function was performed using a metastatic nude mouse model. The result showed that the pancreatic cancer tissues had significantly higher MLPH expression levels than the noncancerous pancreatic tissues. MLPH expression changes were related to PAAD cell proliferation, invasion, and migration. The western blotting demonstrated that PAAD cells had reduced Epithelial-mesenchymal transition (EMT)-related marker expression. Furthermore, overexpressing MLPH enhanced cell proliferation, migration, and invasion, and increased EMT-related marker expression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the molecular mechanism underlying the effect of MLPH on PAAD was significantly related to the PI3K-AKT pathway. LY294002 blocked the MLPH overexpression-mediated enhanced cell invasion and migration and inhibited EMT-associated marker expression. Conversely, 740Y-P reversed the inhibitory effects of MLPH downregulation and led to cell migration, invasion, and EMT. MLPH regulated EMT to mediate PAAD cell invasive migration through the PI3K-AKT pathway. The results indicated that MLPH is a possible target for blocking PAAD metastasis.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis of the role of α2C-adrenergic receptor (ADRA2C) in human tumors and validation in glioblastoma multiforme models.","authors":"Xiaoxiao Zhang, Huitong Chen, Chenyang Wang, Chan Chen, Liyan Liu, Shuangfa Nie, Xiang Gao, Ning Huang, Junli Chen","doi":"10.7150/jca.98240","DOIUrl":"10.7150/jca.98240","url":null,"abstract":"<p><p><b>Background:</b> Several studies have reported the relationship between α2C-adrenergic receptor (ADRA2C) and both neoplastic and non-neoplastic diseases. However, a comprehensive pan-cancer analysis is currently lacking. <b>Methods:</b> Utilizing the RNA sequencing (RNA-seq) datasets from The Cancer Genome Atlas (TCGA) database, the roles of ADRA2C in human pan-cancer were analyzed through a variety of bioinformatics approaches, including R programming language and single-cell sequencing data analysis, <i>et al</i>. Besides, cell migration assay and immunochemistry were employed to further validate the role of ADRA2C in glioblastoma multiforme (GBM) cell lines and GBM mouse model. <b>Results:</b> A total of 33 cancer types were involved in this study. It was revealed that the expression level of ADRA2C varied across different clinical stages in patients with breast invasive carcinoma (BRCA), esophageal adenocarcinoma (ESCA), kidney renal papillary cell carcinoma (KIRP) and lung squamous cell carcinoma (LUSC). Meanwhile, it was found that ADRA2C may play roles in prognosis of adrenocortical carcinoma (ACC), glioblastoma multiforme and lower grade glioma (GBM-LGG), and uveal melanoma (UVM). Functional enrichment analysis suggested that ADRA2C expression level was highly correlated with neuronal system-related pathways. Moreover, ADRA2C may be a promising diagnostic marker for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), GBM, GBMLGG, kidney chromophobe (KICH), and KIRP. Additionally, ADRA2C expression level was correlated with the levels of several infiltrating cells and immune checkpoint genes. Besides, the single-cell sequencing data analysis indicated that ADRA2C played a role in multiple tumor development processes in GBM, retinoblastoma (RB), and UVM. Finally, <i>in vitro</i> and <i>in vivo</i> experiments confirmed that the expression level of ADRA2C may be associated with glioma cell migration, apoptosis, and invasion. <b>Conclusion:</b> ADRA2C exhibited to play a notable role in several cancer types, suggesting that ADRA2C could serve as a promising biomarker or target for cancer diagnosis, prognosis, and treatment, particularly for GBM.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}