Translational cancer research最新文献

{"title":"Diagnostics and immunological function of CENPN in human tumors: from pan-cancer analysis to validation in breast cancer.","authors":"Yubo Jing, Yiyang Wang, Yongxiang Li, Xinzhu Huang, Junyi Wang, Dlraba Yelihamu, Chenming Guo","doi":"10.21037/tcr-24-1291","DOIUrl":"10.21037/tcr-24-1291","url":null,"abstract":"<p><strong>Background: </strong>Centromere protein N (<i>CENPN</i>), a member of the centromere protein family, contributes to ribonucleic assembly, mitosis progression, and chromosome separation. <i>CENPN</i> manifests a close link with the occurrence and progression of several malignant cancers, but there is no pan-cancer study on <i>CENPN</i>, and we aim to ascertain the connection between <i>CENPN</i> and human cancer prognosis and immunotherapy.</p><p><strong>Methods: </strong>The <i>CENPN</i> function in multiple malignant tumors was comprehensively investigated with data from The Cancer Genome Atlas (TCGA) and integrated Gene Expression Omnibus (GEO) database. We examined the transcriptional level, prognostic effect, diagnostic value, genetic and epigenetic alteration, methylation level, and immunological importance of <i>CENPN</i>. Furthermore, this work provided further confirmation of the phenotypic regulating function of <i>CENPN</i> in breast cancer (BC) cells.</p><p><strong>Results: </strong><i>CENPN</i> exhibited significant upregulation in diverse cancer tissues and had different expression patterns across immunological and molecular subgroups in several cancer types. Elevated expression of <i>CENPN</i> may correlate with a worse prognosis. <i>CENPN</i> effectively differentiates most cancers from healthy tissues. Hypomethylate was shown to be <i>CENPN</i> promoter in most cancers. <i>CENPN</i> was shown to be connected with levels of different immune cell infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Set Enrichment Analysis (GSEA) analysis suggested that <i>CENPN</i> may mediate neutrophil extranuclear trap formation, cell cycle, and P53 signaling pathways in cancer. <i>In vitro</i> studies showed that the overexpression of <i>CENPN</i> promotes the proliferation, invasion, and migration of BC cells, while concurrently inhibiting their apoptosis.</p><p><strong>Conclusions: </strong><i>CENPN</i> may operate as a novel predictive indicator and molecular target for targeted therapy in pan-cancer. Significantly, <i>CENPN</i> contributed to controlling the BC growth and advancement.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"881-906"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658719","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":"<i>CALD1</i> inhibits invasion of human ovarian cancer cells by affecting cytoskeletal structure and the number of focal adhesion.","authors":"Yongchao Li, Zhao Yang, Menglong Xu, Haocheng Guan, Zhenhui Wu, Shuwei Li","doi":"10.21037/tcr-24-1375","DOIUrl":"10.21037/tcr-24-1375","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OV) is associated with the highest mortality rate among gynecological cancers, largely due to late diagnosis and chemoresistance. The identification of novel diagnostic markers and therapeutic targets is crucial. Caldesmon 1 (<i>CALD1</i>), a cytoskeleton-regulating protein, has been implicated in various cancers. This study aims to investigate the expression and functional significance of <i>CALD1</i> in OV, focusing on its potential impact on cell invasion and metastasis.</p><p><strong>Methods: </strong>We analyzed <i>CALD1</i> expression using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, along with tissue microarray immunohistochemistry (IHC). Drug sensitivity analysis was performed using the 'oncopredict' R package. A <i>CALD1</i> gene network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. SK-OV-3 cell lines with stable <i>CALD1</i> knockdown were established and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB). We then assessed cell invasiveness using Transwell assays and visualized cytoskeletal changes through immunofluorescence staining of F-actin and Vinculin.</p><p><strong>Results: </strong>The expression of <i>CALD1</i> was significantly reduced in OV tissues compared to normal tissues. Patients with high and low expression levels of <i>CALD1</i> showed significant differences in their response to chemotherapeutic drugs. <i>CALD1</i> and its related genes were found to play an essential role in regulating cytoskeleton organization, focal adhesion formation, and cell movement processes. <i>CALD1</i> knockdown cells exhibited a significant reduction in F-actin stress fibers, a loose cytoskeleton structure, decreased Vinculin expression, and enhanced migration ability.</p><p><strong>Conclusions: </strong>Attenuated expression of <i>CALD1</i> in SK-OV-3 cells leads to fewer F-actin stress fibers, reducing the association between the cytoskeleton and Vinculin. This results in reduced cellular focal adhesions and increased invasiveness of SK-OV-3 cells, promoting OV cell metastasis. These findings suggest that <i>CALD1</i> may have important clinical implications in the diagnosis and treatment of OV.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1323-1335"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657202","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":"<i>OPN3</i> enhances the proliferation, migration, and invasion of triple-negative breast cancer cells via the regulation of the TGF-β signaling pathway.","authors":"Yameng Liu, Yue Zhao, Jingjing Zhang, Xiao Wu, Yumei Li, Ke Tang, Zhengquan Han","doi":"10.21037/tcr-24-1374","DOIUrl":"10.21037/tcr-24-1374","url":null,"abstract":"<p><strong>Background: </strong><i>Opsin3</i> (<i>OPN3</i>) belongs to the guanine nucleotide-binding protein-coupled receptor superfamily, implicated in several pathological mechanisms that contribute to tumor development and resistance to treatment. This study examined <i>OPN3</i> expression in triple-negative breast cancer (TNBC) tissues and its function in TNBC cell propagation, invasion, and migration.</p><p><strong>Methods: </strong>The study analyzed OPN3 expression in TNBC patients and its diagnostic value using immunohistochemistry (IHC) staining and The Cancer Genome Atlas (TCGA) data. To evaluate the impact of <i>OPN3</i> on the growth, invasion, and migration of TNBC cells, both <i>in</i> <i>vitro</i> and <i>in</i> <i>vivo</i> experiments were carried out. The biological mechanisms of <i>OPN3</i>-induced cell migration and invasion were evaluated <i>via</i> quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) analyses.</p><p><strong>Results: </strong>In this study, <i>OPN3</i> upregulation in TNBC tissues was found to be correlated with decreased overall survival (OS) and progression-free survival (PFS) rates. The propagation, invasion, and migration of BT-549 cells were promoted and apoptosis was reduced after <i>OPN3</i> overexpression. It was silenced in BT-549 cells, which resulted in the opposite effects. Further, the transforming growth factor-beta (TGF-β)/SMAD2 signaling pathway was stimulated and the epithelial-mesenchymal transition (EMT) was modulated by <i>OPN3</i> overexpression in BT-549 cells.</p><p><strong>Conclusions: </strong>The findings revealed that <i>OPN3</i> is involved in the stimulation of the TGF-β/SMAD2 signaling pathway, which promotes the growth, migration, and dissemination of TNBC cells. Moreover, <i>OPN3</i> can serve as a diagnostic biomarker and a treatment target for TNBC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1141-1156"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658016","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":"Characterization of immune landscape and prognostic value of IL-17-related signature in invasive breast cancer.","authors":"Wenge Dong, Xiaojie Gu, Jiejing Li, Zhigang Zhuang","doi":"10.21037/tcr-24-1632","DOIUrl":"10.21037/tcr-24-1632","url":null,"abstract":"<p><strong>Background: </strong>Recently, interleukin 17 (IL-17) has been found to play a critical role in the development of breast cancer. However, its prognostic significance in invasive breast cancer (IBC) remains unclear. This study aims to determine the role of IL-17-related signatures in IBC to identify novel therapeutic options.</p><p><strong>Methods: </strong>IBC data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used to identify IL-17-related prognostic genes. A predictive model was developed using TCGA data and validated using METABRIC data. The relationship between IL-17 scores and immune landscape, chemotherapy drug sensitivity [half maximal inhibitory concentration (IC50)], and immune checkpoint gene expression was analyzed. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate key gene expression in breast tumor and normal tissue samples.</p><p><strong>Results: </strong>The predictive model identified core IL-17-related prognostic genes and successfully estimated the prognosis of IBC patients. The model's validity was confirmed using METABRIC data. Patients with high IL-17 scores had worse overall survival (OS) compared to those with low IL-17 scores. Low IL-17 scores were associated with higher immune checkpoint gene expression and predicted enhanced responses to cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death protein 1 (PD-1) therapies. Patients with low IL-17 scores exhibited a higher abundance of immune microenvironment components. Furthermore, qRT-PCR confirmed the lower expression of <i>OR51E1, NDRG2, RGS2</i>, and <i>TSPAN7</i> in breast tumors compared to normal tissue.</p><p><strong>Conclusions: </strong>IL-17-related signatures are promising biomarkers for predicting the prognosis of IBC patients. These findings suggest that IL-17-related markers could be used to guide individualized therapeutic strategies, potentially improving outcomes for IBC patients.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"907-929"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658594","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":"Analysis of risk and prognostic factors for pulmonary metastasis in gastric cancer: a study based on the Surveillance, Epidemiology, and End Results database.","authors":"Wei Kong, Su Yan","doi":"10.21037/tcr-24-2019","DOIUrl":"10.21037/tcr-24-2019","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Pulmonary metastasis in patients with gastric cancer (GC) is closely associated with adverse clinical outcomes and reduced survival rates. This study aimed to investigate the incidence, risk factors, and prognostic factors of pulmonary metastasis in GC patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective cohort study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2021), involving 48,474 GC patients, of whom 2,694 (5.56%) had pulmonary metastasis. Descriptive statistics, multivariable logistic regression, and Cox regression analyses were performed using R software, complemented by Kaplan-Meier survival curves and receiver operating characteristic curve construction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Logistic regression revealed that the risk of pulmonary metastasis was significantly higher in patients with squamous cell carcinoma than adenocarcinoma [adjusted odds ratio (aOR) 1.575, 95% confidence interval (CI): 1.152-2.120], while other pathological types showed a lower risk (aOR 0.269, 95% CI: 0.214-0.333). Stage T4 patients had a significantly higher risk than T1 (aOR 1.487, 95% CI: 1.130-1.954). Surgical intervention (aOR 0.198, 95% CI: 0.145-0.265) and clearance of four or more lymph nodes (aOR 0.489, 95% CI: 0.330-0.725) were associated with reduced pulmonary metastasis risks. Conversely, patients with liver, brain, and bone metastases exhibited significantly increased risks of pulmonary metastasis (aOR 3.888, 95% CI: 3.568-4.238; aOR 4.434, 95% CI: 3.480-5.631; and aOR 2.883, 95% CI: 2.568-3.234, respectively). Multivariate Cox regression analysis of overall survival (OS) and cancer-specific survival (CSS) demonstrated that patients with other epithelial tumors had significantly higher mortality risks [hazard ratio (HR) 1.194, 95% CI: 1.019-1.399; HR 1.191, 95% CI: 1.006-1.409]. Conversely, surgical treatment significantly reduced mortality risks (HR 0.632, 95% CI: 0.473-0.843; HR 0.659, 95% CI: 0.486-0.894), as did chemotherapy (HR 0.322, 95% CI: 0.295-0.351; HR 0.336, 95% CI: 0.307-0.369). Single patients (never married) exhibited higher mortality risks (HR 1.142, 95% CI: 1.020-1.278; HR 1.159, 95% CI: 1.030-1.305), as did patients with liver metastasis (HR 1.240, 95% CI: 1.144-1.344; HR 1.275, 95% CI: 1.171-1.388). Patients with primary lesions located in the lower stomach showed increased mortality risk (HR 1.289, 95% CI: 1.110-1.496; HR 1.203, 95% CI: 1.026-1.410), and those with bone metastases also increased OS mortality risk (HR 1.183, 95% CI: 1.071-1.307). The median OS for patients with pulmonary metastasis was 2 months, compared to 14 months for those without (P&lt;0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Surgical treatment and chemotherapy significantly prolonged OS and CSS. Pulmonary metastasis in GC is associated with extremely poor survival rates. Comprehensive screening for high-risk patients, combined with detailed clinical and pathologi","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"990-1007"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658622","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":"Androgen receptor expression distribution characteristics in young female breast cancer patients in China: a study of clinicopathological features.","authors":"Jianhong Tu, Xiyan Li, Yuexia Chen, Wei Qu, Dan Gong, Adam Ofri, Rainer J Klement, Swarna Lakshmi Arumugam, Yao Zhou","doi":"10.21037/tcr-2025-147","DOIUrl":"10.21037/tcr-2025-147","url":null,"abstract":"<p><strong>Background: </strong>The expression of androgen receptor (AR) in breast cancer has potential implications for predicting clinical outcomes, especially amongst young female patients. Numerous studies have reported that the co-expression of AR with hormone receptors (HRs) is correlated with a favorable prognosis in breast cancer. However, research on the frequency and distribution of AR expression in Chinese breast cancer patients is limited. This study aims to investigate the relationship between AR expression and the expression of progesterone receptor (PR), estrogen receptor (ER), P53, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) in breast cancer patients, and the distribution of molecular subtypes of breast cancer. Further, we aim to explore the pattern of AR expression and its correlation with clinicopathological features and prognosis among young female patients in China.</p><p><strong>Methods: </strong>Formalin-fixed paraffin-embedded tissue samples from 321 young female breast cancer patients were collected from the Third Hospital of Nanchang. Immunohistochemistry was used to assess the expression of AR, ER, PR, HER2, and Ki67. A statistical analysis was conducted to explore the correlation between the expression of AR and these molecular markers, as well as their distribution across different molecular subtypes of breast cancer, and their prognostic significance.</p><p><strong>Results: </strong>A total of 321 breast cancer patients were included in this study. Significant correlations were found between the positive expression of AR and the high expression of PR and ER (P<0.001). The rate of P53 positivity was significantly higher in the AR-positive patients than the AR-negative patients (P=0.01). Additionally, HER2 expression was significantly higher in the AR-positive patients than the AR-negative patients (P<0.001). Notably, the rate of EGFR positivity was significantly lower in the AR-positive patients compared to AR-negative patients (P<0.001). In relation to the molecular subtypes, AR positivity was significantly associated with the luminal A subtype (P<0.001), while the triple-negative breast cancer (TNBC)/basal-like subtype was more common in the AR-negative patients.</p><p><strong>Conclusions: </strong>This study revealed that in young female breast cancer patients in China, AR-positive breast cancer was significantly associated with the high expression of HRs, increased P53 expression and reduced EGFR expression. The expression status of AR can serve as a biomarker to predict therapeutic responses but could also influence the classification of molecular subtypes and the selection of treatment strategies.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1388-1400"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic significance of fragile X mental retardation syndrome-related protein 1 (FXR1) in breast cancer.","authors":"Ohud A Alsalmi, Abrar I Aljohani, Afaf A Alharthi, Amal F Gharib, Abdulrahman R Alrubayee, Ramy M Abbas, Meshari A Alsuwat, Khalid J Alzahrani, Batool S Alsaleh","doi":"10.21037/tcr-24-1542","DOIUrl":"10.21037/tcr-24-1542","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is a highly heterogeneous disease with variable histological appearance, biological features, clinical outcomes, and treatment responses. The number of BC cases in Saudi Arabia has more than tripled during the last 17 years to constitute 30% of all cancer cases in women. Therefore, greater efforts are needed to evaluate prognostic factors for BC in Saudi Arabia to improve prognostication and provide more personalized therapy. Recently, fragile X mental retardation syndrome-related protein 1 (FXR1) was identified as a novel biomarker that contributes to oncogenesis; however, its role in BC has not been well studied. This study aims to evaluate the clinicopathological significance of FXR1 in women with primary BC.</p><p><strong>Methods: </strong>The protein levels of FXR1 in BC tissue samples (n=100) were determined immunohistochemically. The associations between FXR1 levels and clinicopathological parameters and outcomes were evaluated, and significant associations were validated by assessing <i>FXR1</i> mRNA levels in publicly available cohorts in the BC Gene-Expression Miner database (version 5).</p><p><strong>Results: </strong>High protein levels of <i>FXR1</i> were significantly associated with tumor aggressiveness, including stage IIB and IIIC and hormone receptor negativity, the triple-negative BC (TNBC) subtype, and poor outcomes. Consistent with the protein results, high mRNA levels of FXR1 were significantly associated with hormone receptor negativity and the TNBC subtype.</p><p><strong>Conclusions: </strong>This study revealed that FXR1 is a prognostic factor for poor prognosis in women with BC. Further functional studies are needed to confirm its role in aggressive BC and its value as a therapeutic target.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"980-989"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658637","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":"Vanillic acid inhibits TGF-β type I receptor to protect bone marrow mesenchymal stem cells from radiation-induced bystander effects.","authors":"Ting Zhou, Yi-Ming Zhang, Gu-Cheng Zhou, Fu-Xian Liu, Zhi-Ming Miao, Li-Ying Zhang, Yang-Yang Li, Zhi-Wei Liu, Shang-Zu Zhang, Jing Li, Fan Niu, Yan Chen, Yong-Qi Liu","doi":"10.21037/tcr-24-1080","DOIUrl":"10.21037/tcr-24-1080","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is a major treatment option for non-small cell lung cancer (NSCLC); however, irradiated tumor cells can damage non-irradiated cells through radiation-induced bystander effects (RIBE), which can affect the therapeutic efficacy. The study aimed to investigate the mechanism underlying RIBE and the protective effects of vanillic acid (VA) on human bone marrow mesenchymal stem cells (BMSCs).</p><p><strong>Methods: </strong>We established two irradiation models to investigate RIBE. First, we established the A549 cell irradiation model alone, and tested the expression of cathepsin B (CTSB) and transforming growth factor-beta 1 (TGF-β1) by western blot and immunofluorescence staining. Next, we established a co-culture model of A549 cells and BMSCs. After 2 Gy X-rays irradiation of A549 cells, BMSCs cell viability was detected using Cell Counting Kit-8 (CCK-8), reactive oxygen species (ROS) level was detected using flow cytometry, and CTSB, TGF-β type I receptor (TGFβRI), p62 (sequestosome 1), BECLIN1, microtubule-associated protein light chain 3 (LC3), etc., were detected using western blot. Phosphorylated histone H2AX (γH2AX), CTSB, lysosomal-associated membrane protein 1 (LAMP1), and TGFβRI expression levels were detected by immunofluorescence staining. Molecular docking and molecular dynamics simulation, and a CCK-8 assay were used to screen for molecules from <i>Astragalus membranceus</i> that inhibited TGFβRI activity, to protect BMSCs from RIBE. Lastly, we validated VA activity <i>in vivo</i>.</p><p><strong>Results: </strong>In this study, 2 Gy X-rays radiation on A549 cells was found to result in an increase in CTSB and TGF-β1, while CTSB inhibitor CA074Me reduced the radiation-induced TGF-β1 increase. In the co-culture model of A549 cells and BMSCs, 2 Gy X-rays radiation on A549 cells resulted in increase of TGFβRI expression in BMSCs, which led to an increase in ROS, and resulted in DNA damage and the inhibition of BMSCs proliferation. The small molecule VA from <i>Astragalus membranaceus</i> inhibited TGFβRI activity and restored the proliferation of BMSCs.</p><p><strong>Conclusions: </strong>Our findings reveal that radiation causes CTSB overexpression in A549 cells, which further promotes TGF-β1 expression. TGF-β1 activates its receptors on BMSCs to increase ROS levels in BMSCs, while reducing lysosomal double-chain CTSB (dc-CTSB), which results in decreased BMSCs autophagy and an inability to clear ROS, and thus inhibits proliferation. VA inhibits TGFβRI to restore the proliferation of BMSCs, and <i>in vivo</i>, VA can enhance the killing effect of radiation on tumors.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1223-1236"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658644","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":"Oncogenic role and prognostic significance of PIMREG in melanoma.","authors":"Xiao Wei, Yujia Jiang, Tianxiang Xia, Jun Du","doi":"10.21037/tcr-24-1861","DOIUrl":"10.21037/tcr-24-1861","url":null,"abstract":"<p><strong>Background: </strong>Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) plays a significant role in metaphase-to-anaphase transition in cell cycle. Its aberrant expression has been reported to be in correlation with the development of several tumors. However, its role in melanoma remains unknown. This study aimed to investigate the diagnostic and prognostic roles of PIMREG in skin cutaneous melanoma (SKCM).</p><p><strong>Methods: </strong>The expression levels of PIMREG were analyzed in SKCM using datasets downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO). The diagnostic accuracy was assessed using the receiver operating characteristic (ROC) curve. PIMREG was correlated to the functional states of SKCM cells using CancerSEA. Additionally, a protein-protein interaction network was constructed using STRING (https://cn.string-db.org), and hub genes were identified using Cytoscape. Enrichment analysis through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) was utilized to explore the potential functions of PIMREG. The single-sample GSEA (ssGSEA) method was employed to investigate the correlation between PIMREG expression and the level of immune infiltration in SKCM. Drug sensitivity and resistance were analyzed using GSCALite and Cellminer.</p><p><strong>Results: </strong>The expression of PIMREG was significantly higher in SKCM tissues. Its overexpression correlated with poor survival outcome in melanoma patients. ROC analysis also revealed that PIMREG had high diagnostic potential, with area under the ROC curve (AUC) value of 0.874. Multivariate regression also identified PIMREG could serve as an independent diagnostic indicator for SKCM. Using the web tool of CancerSEA, we demonstrated that PIMREG is involved in cell cycle, DNA repair, DNA damage, epithelial-mesenchymal transition (EMT), invasion, and proliferation. Functional enrichment analysis revealed that PIMREG might be correlated with some biological processes (BPs) and important pathways related to cancer, including Wnt signaling and epidermis development.</p><p><strong>Conclusions: </strong>PIMREG is a promising diagnostic and prognostic biomarker and may be regarded as a possible therapeutic target for SKCM.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1070-1084"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658239","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":"PRSS3 is a potential prognostic biomarker for lung adenocarcinoma.","authors":"Lu Nie, Xueqing Zhang, Jie Wu","doi":"10.21037/tcr-24-1556","DOIUrl":"10.21037/tcr-24-1556","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is a highly prevalent and deadly form of lung cancer and is a significant health concern worldwide. Although the expression of serine protease 3 (PRSS3) is elevated in certain cancers, its function in LUAD is yet unclear. The aim of this study was to investigate the mechanism of PRSS3 in lung adenocarcinoma, and validate PRSS3 as a reliable prognostic biomarker in lung adenocarcinoma.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) provides RNA expression data and patient medical information for LUAD patients. To determine which genes are expressed differently in LUAD and normal lung tissues, we carefully examined these data. We then used Cox regression analysis to examine the expression and survival data to pinpoint the genes that are strongly associated with patient survival. The PRSS3 gene affects patient prognosis. Afterward, we divided LUAD patients into low- and high-expression groups on the basis of the median PRSS3 expression to examine the relationship between immune cells and PRSS3. The results of the CIBERSORT and CIBERSORTx studies revealed correlations between PRSS3 and the degree of infiltration of several immune cell types. After the groups with low and high PRSS3 expressions were compared, PRSS3-related genes were identified, and functional enrichment analysis was performed. Furthermore, a model was developed to predict patient prognosis according to clinical characteristics and PRSS3 expression. After the bioinformatics analyses were completed, we validated the differential expression of PRSS3 in samples obtained from our center via Western blotting and immunohistochemistry (IHC).</p><p><strong>Results: </strong>We found that PRSS3 expression is highly upregulated in LUAD and that high PRSS3 expression is associated with a poorer prognosis in the TCGA database. Single-sample gene enrichment analysis revealed a strong correlation between PRSS3 and the immunological microenvironment. The clinical model developed on the basis of the PRSS3 showed great accuracy and can be used as a significant diagnostic indicator for LUAD. Western blotting and IHC confirmed a substantial increase in PRSS3 expression in LUAD. Herein, we analyzed an available dataset for a clinical cohort and revealed that elevated levels of PRSS3 are indicative of unfavorable outcomes in patients diagnosed with LUAD.</p><p><strong>Conclusions: </strong>PRSS3 is significantly upregulated in LUAD and can be used as a marker for LUAD diagnosis and prognosis assessment. Further study of PRSS3 could provide valuable insight into the mechanisms underlying the occurrence and progression of LUAD.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1124-1140"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658422","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}