NeoplasmaPub Date : 2024-12-01DOI: 10.4149/neo_2024_241030N441
Estera Bubláková, Miroslava Makohusová, Anna Ballová, Kristína Husáková, Stanislava Hederová, Andrea Mocná, Robert Chrenko, Svorad Trnovec, Salome Jakešová, Matúš Durdík, Boris Rýchly, Andrea Hrašková, Alexandra Kolenová
{"title":"Clinical features, treatment modalities, and survival rates of pediatric central nervous system tumors: A retrospective analysis from a single center (2000-2020).","authors":"Estera Bubláková, Miroslava Makohusová, Anna Ballová, Kristína Husáková, Stanislava Hederová, Andrea Mocná, Robert Chrenko, Svorad Trnovec, Salome Jakešová, Matúš Durdík, Boris Rýchly, Andrea Hrašková, Alexandra Kolenová","doi":"10.4149/neo_2024_241030N441","DOIUrl":"10.4149/neo_2024_241030N441","url":null,"abstract":"<p><p>Pediatric central nervous system (CNS) tumors represent 20-25% of childhood malignancies, with 35-40 new cases annually in Slovakia. Despite treatment advances, high mortality and poor quality of life in a lot of cases persist. This study assesses the clinical features, treatment modalities, and survival rates of pediatric CNS tumor patients in the single largest center in Slovakia. A retrospective analysis was conducted on pediatric CNS tumors from January 1, 2000, to December 31, 2020, at the Department of Pediatric Oncology and Hematology at the National Institute of Children's Diseases in Bratislava, Slovakia. Among 397 patients (242 males, 155 females), the most common histological types were astrocytomas (42.8%), followed by embryonal tumors (18.4%), brain stem tumors (10.3%), and ependymal tumors (8.1%). Tumor locations were supratentorial (48.1%), infratentorial (46.9%), and spinal (4.3%). Surgical interventions included radical excision (30.2%), subtotal/partial excision (41.8%), and biopsy (9.3%). Treatment modalities varied, with 31.2% receiving combined surgery, chemotherapy, and radiotherapy; 27.5% surgery alone; 9.6% surgery with radiotherapy; 7.8% chemotherapy only; and 6.3% having no treatment. By 2020, 74.3% of patients were alive, with a 25.7% mortality rate. This study outlines the characteristics of pediatric CNS tumors in Bratislava, highlighting the need for multidisciplinary national and international collaboration to advance diagnosis and treatment. Our data align with global findings from other centers.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 6","pages":"603-609"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008898","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}
NeoplasmaPub Date : 2024-12-01DOI: 10.4149/neo_2024_240604N243
Jie Lin, Qiuping Zhu, Fanlin Zeng
{"title":"hsa_circ_0021727 facilitates esophageal squamous cell carcinoma progression by stabilizing GBX2 mRNA through interacting with EIF4A3.","authors":"Jie Lin, Qiuping Zhu, Fanlin Zeng","doi":"10.4149/neo_2024_240604N243","DOIUrl":"10.4149/neo_2024_240604N243","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) has high mortality. The role and regulatory mechanism of hsa_circ_0021727 (circ_0021727) in ESCC remain largely unknown. This study focused on the undiscovered impact of circ_0021727 on cell cycle progression, apoptosis, and angiogenesis of ESCC. We found that circ_0021727 levels were significantly upregulated in ESCC cells. TUNEL, flow cytometry, and tubule formation assay indicated that knockdown of circ_0021727 in ESCC induced cell arrest at the G0/G1 phase, promoted apoptosis, and inhibited angiogenesis, whereas overexpression of circ_0021727 produced the opposite effect. Gastrulation brain homeobox 2 (GBX2) GBX2 was a downstream target gene of circ_0021727, and overexpression of GBX2 reversed the effect of circ_0021727 knockdown in ESCC progression. The results of the RIP and RNA pull-down showed that circ_0021727 and GBX2 mRNA bound with eukaryotic translation initiation factor 4A3 (EIF4A3). Overexpression of circ_0021727 promoted GBX2 mRNA stability by binding with EIF4A3. In a tumor xenograft model, the knockdown of circ_0021727 inhibited tumor growth, which was reversed by further overexpression of GBX2. In conclusion, circ_0021727 increased GBX2 mRNA stability by recruiting EIF4A3, which promoted cell cycle progression and angiogenesis in ESCC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 6","pages":"581-593"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059784","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}
NeoplasmaPub Date : 2024-12-01DOI: 10.4149/neo_2024_240719N305
Qingqing Zhang, Jun Mao, Luhan Xie, Ying Lu, Xiaobo Li, Xiaotang Yu, Lianhong Li
{"title":"MTHFD2 promotes breast cancer cell proliferation through IFRD1 RNA m6A methylation-mediated HDAC3/p53/mTOR pathway.","authors":"Qingqing Zhang, Jun Mao, Luhan Xie, Ying Lu, Xiaobo Li, Xiaotang Yu, Lianhong Li","doi":"10.4149/neo_2024_240719N305","DOIUrl":"10.4149/neo_2024_240719N305","url":null,"abstract":"<p><p>MTHFD2 is highly overexpressed in breast cancer tissues, indicating that it might be used as a target in breast cancer treatment. This study aims to determine the role of MTHFD2 in breast cancer cell proliferation and the molecular pathways involved. In order to investigate MTHFD2 gene expression and its downstream pathways in breast cancer, we started our inquiry with a bioinformatics analysis. We then engineered breast cancer cell lines with either silenced or overexpressed MTHFD2 to study its effects on the cell cycle, proliferation, and the m6A methylation status of the gene IFRD1, predicted as a downstream target. Overexpression of MTHFD2 enhanced cellular proliferation, increased the proportion of EdU-positive cells, and accelerated progression into the S+G2/M phase. In contrast, MTHFD2 knockdown led to opposite effects. MTHFD2 and IFRD1 expression levels showed a strong positive association. Increased MTHFD2 activity boosted HDAC3 and mTOR phosphorylation, activating p70 S6K and 4EBP1-key regulators of cell proliferation. Moreover, overexpression of MTHFD2 was associated with reduced p53 acetylation and total protein levels. Silencing MTHFD2 decreased m6A methylation of IFRD1 RNA, whereas its overexpression increased methylation. Notably, IFRD1 siRNA transfection reversed the proliferative effects induced by MTHFD2 overexpression. Furthermore, MTHFD2 knockdown enhanced the sensitivity of breast cancer cells to several chemotherapeutic agents. In conclusion, MTHFD2 influences breast cancer cell proliferation by modulating the m6A methylation of IFRD1 RNA, which regulates the HDAC3/p53/mTOR pathway. These findings suggest that MTHFD2 inhibitors may synergistically enhance the efficacy of existing chemotherapies.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 6","pages":"544-558"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008914","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":"Disruption of lipid raft reverses drug resistance in colorectal cancer cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B pathway and P-glycoprotein.","authors":"Jing Chen, Wei Zheng, Qian Li, RanRan Xu, TingTing Bai, Chao Pan","doi":"10.4149/neo_2024_240422N179","DOIUrl":"10.4149/neo_2024_240422N179","url":null,"abstract":"<p><p>Regarding flotillin knockdown, drug resistance is reversed in colorectal cancer (CRC) cell lines; this is associated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, as our previous experimental results indicated. However, the exact mechanism underlying this pathway remains unclear. PI3K inhibitor and activator were added separately to clarify the role of the PI3K pathway in reversing drug resistance. The results showed decreased resistance after inhibiting PI3K activity. Furthermore, the reduced resistance due to flotillin knockdown was restored after adding the PI3K activator. Additional results showed no changes in PI3K molecules. However, p-AKT expression was downregulated. Further results suggested that the phosphatidylinositol (3,4,5)-trisphosphate/phosphatidylinositol 4,5-bisphosphate (PIP3/PIP2) ratio was downregulated, whereas the phosphatase and tensin homolog (PTEN) expression was upregulated. In addition, we also found that P-gp activity inhibition resulted in increased adriamycin accumulation and reversal of resistance, and flotillin knockdown was accompanied by a downregulation of P-gp expression in CRC cells. In conclusion, our study demonstrated that flotillin knockdown could reverse drug resistance in CRC cells by downregulating the PTEN/PI3K/AKT pathway and P-gp.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 6","pages":"571-580"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008902","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":"IFIH1 promotes apoptosis through the TBK1/IRF3 pathway in triple-negative breast cancer.","authors":"Chao Shi, Xiaohan Wang, Jingping Li, Shang Wu, Zhihui Liu, Xiaofei Ren, Xiangmei Zhang, Yunjiang Liu","doi":"10.4149/neo_2024_240614N255","DOIUrl":"10.4149/neo_2024_240614N255","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast malignancy. Although some patients benefit from immune checkpoint therapy, current treatment methods rely mainly on chemotherapy. It is imperative to develop predictors of efficacy and identify individuals who will be sensitive to particular treatment regimens. This study analyzed peripheral interferons and immune cell subsets in TNBC patients receiving pre-operative neoadjuvant therapy. The effects of interferon-induced helicase 1 (IFIH1) on the biological characteristics of apoptosis and PD-L1 expression of cancer cells and its potential mechanism were investigated using bioinformatics analysis, clinical specimens, and in vitro study. We found that serum interferon-γ and interferon-α2 levels were significantly higher in TNBC patients with pathologic complete response (pCR). The expression of IFIH1 is markedly upregulated in various tumors, including breast cancer. Immunohistochemical results revealed that IFIH1 was specifically located in the cytoplasm of cancer cells. Gene set enrichment analysis showed that genes co-expressed with IFIH1 were involved in tumor immune-related pathways and apoptosis. Knockdown of IFIH1 in MDA-MB-231 and BT-549 cells resulted in significantly increased cell proliferation and colony formation. Regarding apoptosis-related pathway proteins, there was a significant decrease in levels of phosphorylated TANK-binding kinase 1 (TBK1) and phosphorylated interferon regulatory factor 3 (IRF3). In addition, the expression of PD-L1 was significantly downregulated. Furthermore, we demonstrated the existence of binding sites between IRF3 and PD-L1 promotors. Our data indicate that cancer cell IFIH1 promotes apoptosis and PD-L1 expression, suggesting its potential as a predictive marker of efficacy and therapeutic target in TNBC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 6","pages":"533-543"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008907","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}
NeoplasmaPub Date : 2024-10-01DOI: 10.4149/neo_2024_240511N214
Jianwang Li, Xiaozhen Cheng, Denggao Huang, Ronghua Cui
{"title":"Six2 regulates the malignant progression and 5-FU resistance of hepatocellular carcinoma through the PI3K/AKT/mTOR pathway and DNMT1/E-cadherin methylation mechanism.","authors":"Jianwang Li, Xiaozhen Cheng, Denggao Huang, Ronghua Cui","doi":"10.4149/neo_2024_240511N214","DOIUrl":"10.4149/neo_2024_240511N214","url":null,"abstract":"<p><p>This study focuses on exploring the role of Six2 in the progression of hepatocellular carcinoma (HCC) and its resistance to the chemotherapy drug 5-fluorouracil (5-FU). Using Hep3B and Huh7 cell lines, we analyzed how Six2 affects various cellular functions, including viability, proliferation, apoptosis, and invasion. Our research also delved into Six2's regulatory impact on DNMT1 levels, E-cadherin expression, and the methylation of the E-cadherin promoter, all of which are crucial for 5-FU resistance in HCC cells. Additionally, we examined the effects of Six2 knockdown on the PI3K/AKT/mTOR signaling pathway. Our findings indicate that overexpression of Six2 enhances cell viability and proliferation, encourages invasive behavior, increases methylation at the E-cadherin promoter, and reduces apoptosis. These changes correspond with increased levels of DNMT1 and decreased levels of E-cadherin, culminating in heightened resistance to 5-FU. Conversely, knocking down Six2 increases the sensitivity of HCC cells to 5-FU and reduces activation of the PI3K/AKT/mTOR pathway. These results suggest that Six2 plays a significant role in promoting HCC proliferation, invasion, and chemotherapy resistance, particularly through mechanisms involving DNMT1 and the PI3K/AKT/mTOR pathway, highlighting its potential as a target for HCC treatment.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 5","pages":"451-462"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646569","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":"Exploring the role of eIF3m in prostate cancer: regulation of c-Myc signaling pathway and therapeutic implications.","authors":"Dongdong Guo, Cheng Ma, Jianyi Gu, Xinyu Zhai, Xinlin Chen, Guanqun Ju, Chuanmin Chu, Xiangyang Zhan, Tao Wang, Mingyue Tan, Dongliang Xu","doi":"10.4149/neo_2024_240603N242","DOIUrl":"10.4149/neo_2024_240603N242","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in males, and there are currently few effective therapeutic targets following hormone therapy resistance. Subunits of eukaryotic initiation factor 3 (eIF3) have been implicated in the progression of various cancers. This study aims to investigate the biological functions of the eIF3m subunit in PCa and assess its potential as a novel therapeutic target for treatment. We utilized open-access datasets and patient tissues to analyze the expression and prognostic value of eIF3m in PCa. To explore the role of eIF3m in PCa growth, we established eIF3m knockdown models in PC3 and 22Rv1 cells for both in vitro and in vivo studies. Gene set enrichment analysis (GSEA) was utilized to identify signaling pathways regulated by eIF3m in PCa. Additionally, western blotting and immunochemistry were used to confirm the regulation of c-Myc signaling by eIF3m in PCa. Our results indicated that eIF3m expression was elevated in PCa tissues, with higher levels correlating with an increased risk of biochemical recurrence following radical prostatectomy. Both in vitro and in vivo experiments demonstrated that inhibiting eIF3m significantly impeded the growth of PCa cells. GSEA and immunochemistry further revealed that high eIF3m expression contributed to the activation of c-Myc signaling in PCa patients. Notably, the downregulation of eIF3m resulted in a significant decrease in the expression of c-Myc mRNA and protein in PCa cells. Overall, our findings suggest that eIF3m inhibition significantly suppressed PCa cell growth and c-Myc signaling, indicating that eIF3m is a promising therapeutic target for PCa patients.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 5","pages":"442-450"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648579","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}
NeoplasmaPub Date : 2024-10-01DOI: 10.4149/neo_2024_240716N299
Xiaobing Li, De Wu, Jing Tang, Yuebing Wu
{"title":"Albumin bound-paclitaxel combined with anlotinib and immunotherapy in the second-line treatment of ES-SCLC: a retrospective cohort study.","authors":"Xiaobing Li, De Wu, Jing Tang, Yuebing Wu","doi":"10.4149/neo_2024_240716N299","DOIUrl":"10.4149/neo_2024_240716N299","url":null,"abstract":"<p><p>Effective treatment strategies for second-line therapy in extensive-stage small cell lung cancer (ES-SCLC) are currently lacking. For this reason, we collected and recorded efficacy and safety data from patients with ES-SCLC who had disease progression after first-line treatment and received albumin-bound paclitaxel, anlotinib, and immunotherapy. Preliminary data showed an objective response rate of 37.78%. Median progression-free survival and overall survival were 5 months and 10 months, respectively. Treatment-related adverse events were mostly tolerable. Subgroup analysis indicated that efficacy correlated with the interval from last chemotherapy to treatment initiation and specific drug-related adverse events. Further analysis of immune cell subtypes suggested that the mechanism may involve depletion of immune suppression to activate immune responses synergistically against tumors. With its promising efficacy and manageable adverse effects, this regimen holds potential as a significant option for second-line therapy in ES-SCLC. However, due to the limited sample size, further clinical validation is needed to ascertain its true clinical value.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 5","pages":"482-489"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648537","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}
NeoplasmaPub Date : 2024-10-01DOI: 10.4149/neo_2024_240802N325
Zhenghong Huang, Wanxin Zhang, Kun Huang, Jiafu Feng
{"title":"Determination of serum vitamin D in patients with renal, bladder, and prostate cancer by ultra-performance liquid chromatography-tandem mass spectrometry.","authors":"Zhenghong Huang, Wanxin Zhang, Kun Huang, Jiafu Feng","doi":"10.4149/neo_2024_240802N325","DOIUrl":"10.4149/neo_2024_240802N325","url":null,"abstract":"<p><p>The purpose of this study is to detect the vitamin D (VitD) levels in patients with renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PC) using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology to assess the VitD status in subjects using different methods, to understand the true level of VitD in RCC, BC, and PC patients. A total of 170 subjects were included in this study, and their serum VitD metabolite levels were measured, including 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [C3-epi-25(OH)D3, C3-epi], and calculations for 25(OH)D, 25(OH)D2/25(OH)D3, and C3-epi/25(OH)D3 were made. The variations in serum VitD, calcium (Ca), inorganic phosphorus (IP), vitamin D receptor (VDR), and renal function indicators were measured, and their correlations were analyzed. The levels of 25(OH)D, 25(OH)D3, C3-epi, C3-epi /25(OH)D3, and free 25(OH)D [ F25(OH)D] in RCC, BC, and PC patients were significantly lower than that in the healthy control (HC) group (all p<0.05). The ratio of 25(OH)D2/25(OH)D3 was significantly higher in these groups compared to the HC group (all p<0.05). 25(OH)D3 distinguished the HC group from common cancers of the urinary system (including RCC, BC, and PC) in male patients and showed good diagnostic performance. The level of 25(OH)D3 in all three groups was positively correlated with F25(OH)D levels, and in the disease groups, C3-epi levels were positively correlated with both 25(OH)D3 and F25(OH)D levels. This study found that RCC, BC, and PC patients had lower serum levels of 25(OH)D3, C3-epi, and F25(OH)D compared to healthy individuals, with most RCC, BC, and PC patients displaying VitD deficiency.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 5","pages":"463-472"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648570","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}
NeoplasmaPub Date : 2024-10-01DOI: 10.4149/neo_2024_240701N280
Eunah Shin, Ja Seung Koo
{"title":"Protein level of epithelial membrane protein (EMP) 1, EMP 2, and EMP 3 in carcinoma of unknown primary.","authors":"Eunah Shin, Ja Seung Koo","doi":"10.4149/neo_2024_240701N280","DOIUrl":"10.4149/neo_2024_240701N280","url":null,"abstract":"<p><p>Carcinoma of unknown primary (CUP) is defined as a metastatic carcinoma whose primary site cannot be determined, and the absence of a known primary tumor in CUP poses a significant challenge in treatment planning. The purpose of this study was to investigate the protein level of epithelial membrane proteins (EMP) 1, EMP 2, and EMP 3 in CUP and explore their clinical implications. Tissue microarrays were constructed using samples from 72 CUP cases. The histologic subtypes were adenocarcinoma (ADC) in 22% of cases, poorly differentiated carcinoma (PDC) in 15%, squamous cell carcinoma (SCC) in 19%, and undifferentiated carcinoma (UDC) in 14%. Clinically, 17 cases (23.6%) were of favorable type, and 55 cases (76.4%) were of unfavorable type. Immunohistochemical staining for EMP 1, EMP 2, and EMP 3 was performed on the tissue microarrays to investigate the correlation between staining results and clinicopathologic parameters. The investigation of EMP 1, EMP 2, and EMP 3 protein levels in CUP revealed that EMP 2 H-score was significantly higher (p=0.013) in the favorable type, and there was a higher proportion of stromal EMP 1-positivity (p=0.034) and high protein level of tumoral EMP 3 (p=0.002). A positive correlation was observed between EMP 1 and EMP 3 (r=0.425 and p<0.001). In conclusion, CUP exhibits EMP 1, EMP 2, and EMP 3 protein levels, and their protein levels are different according to the clinical subtype.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 5","pages":"473-481"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646651","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}