Translational Oncology最新文献

{"title":"Combined anti-leukemic effect of gilteritinib and GSK-J4 in FLT3-ITD+ acute myeloid leukemia","authors":"Qi Zhou ,&nbsp;Yongyu Guan ,&nbsp;Pingping Zhao ,&nbsp;Huiyuan Chu ,&nbsp;Yaming Xi","doi":"10.1016/j.tranon.2025.102271","DOIUrl":"10.1016/j.tranon.2025.102271","url":null,"abstract":"<div><div>Gilteritinib treats acute myeloid leukemia (AML) with the FMS-like receptor tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutation. Dysregulation of histone modification affects the genesis and progression of AML. Strategies targeting key histone regulators have not been applied to the treatment of AML. Lysine demethylase 6B (KDM6B) is dysregulated in a variety of cancers and regulates the expression of oncogenes, which has potential in anticancer therapy. We explored whether GSK-J4 (an inhibitor of the demethylase KDM6B) has an anti-leukemic effect in the gilteritinib treatment of FLT3-ITD⁺ AML and the effect of gilteritinib combined with GSK-J4 in leukemia. In our study, we evaluated the anti-leukemic effect of GSK-J4 in gilteritinib therapy through in vitro and in vivo experiments. The results revealed that the combined treatment of gilteritinib and GSK-J4 has greater anti-proliferation and pro-apoptosis effects than gilteritinib alone. Gilteritinib and GSK-J4 performed synergistically to arrest the cell cycle. Gilteritinib mainly induces cell cycle phase arrest at the S or G0/G1, and GSK-J4 inhibits the cell cycle progression in the S phase and reduces cell viability by reducing the expression of key regulatory factors from the G1 phase to the S phase. At the same time, GSK-J4 enhances the expression of apoptosis-related proteins (Bax and cleavage caspase-9). In addition, gilteritinib or GSK-J4 monotherapy increases reactive oxygen species (ROS) production, and the combination has a synergistic effect, accelerating leukemic cell death. Our study provides proof that the combined therapy of gilteritinib and GSK-J4 has a synergistic antileukemic effect on FLT3-ITD⁺ AML.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102271"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRTX1133 attenuates KRASG12D mutated-colorectal cancer progression through activating ferroptosis activity via METTL14/LINC02159/FOXC2 axis","authors":"Junwei Zou ,&nbsp;Xiuhua Shi ,&nbsp;Zhaoying Wu ,&nbsp;Siyuan Zuo ,&nbsp;Xiaolei Tang ,&nbsp;Hailang Zhou ,&nbsp;Yong Huang","doi":"10.1016/j.tranon.2024.102235","DOIUrl":"10.1016/j.tranon.2024.102235","url":null,"abstract":"<div><div>Colorectal cancer (CRC) ranks as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Studies have shown that CRC patients with KRAS mutations, especially KRAS^G12D, have an increased risk of metastasis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are crucial in the carcinogenesis and progression of various cancers, regulating multiple biological processes but the link between KRAS^G12D mutations and lncRNAs in CRC remains unclear. Therefore, this study was designed to identify a novel lncRNA involved in KRAS^G12D-mutated CRC and to elucidate its molecular mechanisms. The analysis of differentially expressed lncRNAs in the GSE201412 dataset revealed that LINC02159 was significantly upregulated following treatment with the KRAS^G12D inhibitor MTRX1133 Data from the GTEx database indicated that LINC02159 is highly expressed in CRC tumour tissues and is associated with better patient outcomes. In vitro and in vivo experiments suggest that LINC02159 acts as a tumour suppressor in CRC progression. Specifically, LINC02159 knockdown negated the inhibitory effects of MRTX1133 on tumourigenesis and its promotive effect on ferroptosis in KRAS^G12D-mutated CRC cells. LINC02159 expression is regulated by METTL14, with METTL14 knockdown decreasing m6A methylation of LINC02159, leading to its increased expression in CRC cells. Additionally, LINC02159 stabilised FOXC2 expression through de-ubiquitination. Rescue experiments further clarified that the METTL14/LINC02159/FOXC2 signalling axis is crucial for the inhibitory effects of MRTX1133 in KRAS^G12D-mutated CRC. Our study provides novel insights into the therapeutic potential of MRTX1133 in treating KRAS^G12D-mutated CRC by identifying a METTL14/LINC02159/FOXC2 signalling axis that mediates drug response. Our findings highlight the importance of understanding the molecular mechanisms of lncRNAs in cancer to develop effective targeted therapies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102235"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4","authors":"Shaoliang Zhu ,&nbsp;Gang Wang ,&nbsp;Yuxuan Zhang ,&nbsp;Mengjie Zou ,&nbsp;Zhi Li ,&nbsp;Shenhong Qu ,&nbsp;Xiaosu Zou ,&nbsp;Wenqian Nong ,&nbsp;Weiwei Miao ,&nbsp;Qicong Chen ,&nbsp;Juanmei Mo ,&nbsp;Huibing Chen ,&nbsp;Lequn Li ,&nbsp;Xiaofeng Dong ,&nbsp;Honglin Luo","doi":"10.1016/j.tranon.2024.102254","DOIUrl":"10.1016/j.tranon.2024.102254","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) represents a major malignancy globally, characterized by high malignancy and intricate molecular mechanisms. This study aims to explore the role of the long non-coding RNA (lncRNA) lnc-EST885 in HCC development.</div></div><div><h3>Methods</h3><div>Cell experiments including FISH, western blot, flow cytometry and functional analysis were used to elucidate the effects of lnc-EST885 on cell proliferation, apoptosis, migration and EMT processes. RNA pull-down and ESI-FT-ICR-MS were used to identify proteins that interact with lnc-EST885 and were verified by RIP-qPCR. Furthermore, the association of lnc-EST885 and TRAF4 with HCC prognosis and metastasis was evaluated through bioinformatics analysis and animal models.</div></div><div><h3>Results</h3><div>lnc-EST885 is one of the lncRNAs with the highest expression levels in M2-type macrophages. The expression of lnc-EST885 in HCC tissues is significantly higher than in normal tissues, and high expression is associated with poor prognosis. Functional experiments have shown that lnc-EST885 significantly promotes the proliferation and migration of liver cancer cells, inhibits apoptosis, and induces EMT. Studies in a mouse lung metastasis model have also confirmed that lnc-EST885 promotes the pulmonary metastasis of HCC cells in vivo. Mechanistic studies have revealed that lnc-EST885 can bind to the TRAF4 protein, activating the PI3K/AKT signaling pathway, thereby promoting the proliferation, migration, and EMT capability of liver cancer cells, contributing to the malignant phenotype of HCC.</div></div><div><h3>Conclusion</h3><div>lnc-EST885 plays a crucial role in the development of liver cancer, serving as a potential biomarker for predicting HCC prognosis and providing a new target for HCC treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102254"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma","authors":"Bo Li ,&nbsp;Meilong Shi ,&nbsp;Yang Wang ,&nbsp;Penghao Li ,&nbsp;Xiaoyi Yin ,&nbsp;Guoxiao Zhang ,&nbsp;Xiaochao Kang ,&nbsp;Huan Wang ,&nbsp;Suizhi Gao ,&nbsp;Kailian Zheng ,&nbsp;Xiaohan Shi ,&nbsp;Xiongfei Xu ,&nbsp;Yukun Zhou ,&nbsp;Hui Jiang ,&nbsp;Wei Jing ,&nbsp;Shiwei Guo ,&nbsp;Gang Jin","doi":"10.1016/j.tranon.2025.102282","DOIUrl":"10.1016/j.tranon.2025.102282","url":null,"abstract":"<div><div><strong>Purpose</strong> The present study aimed to clarify the distribution pattern of carcinoma associated fibroblasts (CAFs) across pancreatic ductal adenocarcinoma (PDAC) and its prognostic prediction value.</div><div><strong>Methods</strong> Data of two cohorts were retrospectively collected from consecutive patients who underwent primary pancreatic resection from January 2015 to December 2017. We used tumor specimens to screen out the most suitable markers for the spatial distribution analysis for CAFs subpopulations. We utilized a tissue microarray to assess the spatial intensity of α-SMA expression within the tumor microenvironment. Specifically, we classified CAFs into two types based on their α-SMA spatial expression. Type II CAFs were designated as those located in the juxtatumoural stroma with α-SMA expression that was moderate or higher, and those in the peripheral stroma with α-SMA expression that was less than moderate. All other cases, where the α-SMA expression did not meet these criteria, were categorized as Type I CAFs. Multivariable Cox proportional hazards regression was used to assess risk factors associated with patient outcomes. RNA sequencing data were obtained from bulk tumor samples and isolated CAFs from patients to reveal the distinct pattern and elucidated their fundamental characteristics.</div><div><strong>Results</strong> The α-SMA spatial intensity was the most suitable variable for representative of CAFs spatial characteristics. Patients with Type Ⅰ CAFs were more likely to be allocated into N1 or N2 of the N stage and Ⅱ and Ⅲ of the TNM stage. The spatial distribution pattern of CAFs (Type Ⅰ v.s. Type Ⅱ: HR, 1.568; 95 % CI, 1.053–2.334; <em>P</em> = 0.027) was an independent prognostic factor in the discovery cohort, so as in the validation (Type Ⅰ vs. Type Ⅱ: HR, 2.197; 95 % CI, 1.410–3.422; <em>P</em> = 0.001). RNA sequencing analysis revealed that the differentially expressed genes (DEGs) in Type I CAFs are closely associated with those in corresponding tumor tissues, highlighting the enhanced biological significance of immune-related and oncogenic invasive pathways.</div><div><strong>Conclusions</strong> Our findings that two types of α-SMA-positive CAFs with different spatial patterns present heterogeneously across tissues of PDACs and correlated with patients’ outcomes. The spatial location of CAFs may facilitate patients’ selection in precision medicine of PDACs.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102282"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a prognostic and drug sensitivity model for gastric cancer utilizing telomere-related genes","authors":"Xiaoxiao Li ,&nbsp;Xiaoxuan Wang ,&nbsp;Fuxiang Yu ,&nbsp;Zhongguo Li ,&nbsp;Daxin Chen ,&nbsp;Yingxue Qi ,&nbsp;Zhongyu Lu ,&nbsp;Yaqin Liu ,&nbsp;Dongsheng Chen ,&nbsp;Yaoqiang Wu","doi":"10.1016/j.tranon.2024.102232","DOIUrl":"10.1016/j.tranon.2024.102232","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) poses a major global health challenge because of its unfavorable prognosis. Elevated telomerase activity has been linked to the rapid growth and invasiveness of GC tumors. Investigating the expression profiles of telomerase could improve our understanding of the mechanisms underlying telomere-related GC advancement and its applicability as potential targets for diverse therapeutic strategies for GC.</div></div><div><h3>Methods</h3><div>The TCGA and GEO databases were utilized to access transcriptome and clinical data related to GC. After assessing differentially expressed genes (DEGs), a prognostic risk model was developed through Cox univariate regression, LASSO–Cox regression. The prognostic risk model was validated using data from the GSE62254 cohort. The significant influence of the risk model on the tumor immune microenvironment (TIME) and its sensitivity to various drugs was assessed.</div></div><div><h3>Results</h3><div>Differential expression analysis identified 328 significantly telomere-related DEGs in GC, with 35 of them showing a significant association with GC prognosis. A predictive risk model composed of four telomere-related genes (TRGs) was established, enabling the accurate stratification of GC patients into two distinct prognostic groups. The LASSO risk model demonstrated notable variations in immune-cell infiltration and drug sensitivity patterns between high- and low-risk groups.</div></div><div><h3>Conclusions</h3><div>The study establishes suggestive relationships between four TRGs (<em>LRRN1, SNCG, GAMT</em>, and <em>PDE1B</em>) and the prognosis of GC. The comprehensive characterization of the TRG model reveals their possible roles in the prognosis, TIME, and drug sensitivity in GC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102232"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of S100A8/A9 and neutrophils as prognostic markers in metastatic melanoma patients under immune-checkpoint inhibition","authors":"Yasmin F Melzer ,&nbsp;Nadine L Fergen ,&nbsp;Christian Mess ,&nbsp;Julia-Christina Stadler ,&nbsp;Glenn Geidel ,&nbsp;Ysabel A Schwietzer ,&nbsp;Julian Kött ,&nbsp;Klaus Pantel ,&nbsp;Stefan W Schneider ,&nbsp;Jochen Utikal ,&nbsp;Ewa Wladykowski ,&nbsp;Sabine Vidal-y-Sy ,&nbsp;Alexander T Bauer ,&nbsp;Christoffer Gebhardt","doi":"10.1016/j.tranon.2024.102224","DOIUrl":"10.1016/j.tranon.2024.102224","url":null,"abstract":"<div><div>Immune-checkpoint inhibitors (ICIs) have revolutionized melanoma treatment, yet approximately half of patients do not respond to these therapies. Identifying prognostic biomarkers is crucial for treatment decisions. Our retrospective study assessed liquid biopsies and tumor tissue analyses for two potential biomarkers: danger-associated molecular pattern (DAMP) S100A8/A9 and its source, neutrophils. In 43 metastatic unresected stage III/IV melanoma patients, elevated serum levels of S100A8/A9 and neutrophils before and during ICI treatment correlated with worse outcomes. Furthermore, in 113 melanoma patients, neutrophil expression in the tumor microenvironment (TME) was associated with relapse and reduced survival. Measuring S100A8/A9 and neutrophils could enhance immunotherapy monitoring by predicting impaired clinical outcomes and non-response to ICIs. Serum S100A8/A9 levels and neutrophil counts at baseline (T0) and during treatment (T3) correlated with reduced progression-free survival (PFS). Elevated S100A8/A9 levels at T0 and T3 negatively impacted overall survival (OS). Notably, neutrophil infiltration was more prevalent in primary melanomas than in nevi and metastases, and its presence in primary melanomas was linked to poorer survival. S100A8/A9 serum levels, neutrophil counts, and tumor-associated neutrophil infiltration represent promising biomarkers for predicting treatment response and clinical outcomes in melanoma patients receiving ICIs.</div></div><div><h3>Significance</h3><div>These findings underscore the critical need for reliable biomarkers in melanoma research, particularly for predicting responses to immune-checkpoint inhibitors (ICIs). Identifying S100A8/A9 levels and neutrophil infiltration as potential indicators of treatment outcomes offers valuable insights for personalized therapy decisions. By enhancing monitoring and prognosis assessment, these biomarkers contribute to refining treatment strategies, ultimately improving patient care and outcomes. This research bridges gaps in understanding melanoma response mechanisms and highlights avenues for further investigation into immune-related markers, fostering advancements in precision medicine for melanoma patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102224"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma","authors":"Lingling Li ,&nbsp;Xiaocui Bu ,&nbsp;Shuhui Wang ,&nbsp;Yan Liu ,&nbsp;Chongdao Chen ,&nbsp;Wei Zhang ,&nbsp;Peng Zhao","doi":"10.1016/j.tranon.2024.102248","DOIUrl":"10.1016/j.tranon.2024.102248","url":null,"abstract":"<div><div>It has been well established that tumor-infiltrating lymphocytes (TILs) play a critical role in the pathogenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the mechanism on the interactions between TILs and tumor cells in the tumor-immune microenvironment remains unclear. In the present study, the expression of Response Gene to Complement 32 (RGC-32) was evaluated using immunohistochemistry. We analyzed the associations of RGC-32 expression with patient characteristics and survival. We also assessed TILs and their subsets (CD3⁺, CD4⁺, CD8⁺ and PD-1⁺) in the tumor nest. The level of RGC-32 expression was positively correlated with ISUP grade and Ki67 expression and was an independent poor prognosis factor of patients with ccRCC. RGC-32 expression was negatively correlated with the infiltration of TIL and CD3⁺T cells, but positively correlated with infiltration of PD-1⁺cells. In vitro studies showed that RGC-32 expression in renal cancer cells was downregulated by activated immune cells. Further investigation revealed that RGC-32 expression in renal cancer cells was inhibited by TNF-α and IL-1β secreted by activated immune cells. Collectively, these data indicate that RGC-32 could be a novel prognostic and druggable target related to the tumor-immune microenvironment in renal cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102248"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circICMT upregulates and suppresses the malignant behavior of bladder cancer","authors":"Xin Luo ,&nbsp;FangMei Xie ,&nbsp;Guoqiang Qin ,&nbsp;Ge Zou ,&nbsp;Xu Lu ,&nbsp;Chaofeng Zhang ,&nbsp;Zeping Han ,&nbsp;Ying Zhao ,&nbsp;Xiaoyu Song ,&nbsp;WenFeng Luo ,&nbsp;Yongsheng Li ,&nbsp;JinHua He ,&nbsp;Jian Shen","doi":"10.1016/j.tranon.2024.102262","DOIUrl":"10.1016/j.tranon.2024.102262","url":null,"abstract":"<div><h3>Background</h3><div>Circular RNA (circRNA) is a new type of endogenous single-stranded RNA with a covalently closed circular structure. Increasing evidence shows that circRNA plays an important role in regulating gene expression in tumors. circICMT is a circular RNA produced by the ICMT gene. Currently, the molecular function of circICMT in bladder cancer remains unclear.</div></div><div><h3>Method</h3><div>Differentially expressed circRNAs were identified from RNA sequencing data and circICMT was identified as a new candidate circRNA. qRT-PCR and sanger sequencing were used to detect the expression of circICMT in bladder cancer tissue specimens. Stable cell lines overexpressing and knocking down circICMT were constructed to explore the effect of circICMT on bladder cancer cells. Its biological effects were detected through wound healing experiments, colony formation experiments, CCK-8 experiments and xenogeneic tumorigenesis experiments.</div></div><div><h3>Result</h3><div>This study found that circICMT was significantly upregulated in bladder cancer tissue specimens. Overexpression of circICMT can inhibit cell migration, proliferation and colony formation ability, while knockdown of circICMT promotes the malignant phenotype of bladder cancer cells. Bioinformatics predictions have found that circICMT can bind to a variety of miRNAs and RBPs and may form a complex regulatory network to regulate the progression of bladder cancer.</div></div><div><h3>Conclusion</h3><div>circICMT is significantly highly expressed in bladder cancer, and intervening circICMT expression affects the malignant phenotype of bladder cancer cells in vivo and in vitro, which may provide potential biomarkers and therapeutic targets for the management of bladder cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102262"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of perioperative circulating CD56bright NK cell and recovery of NK cell activity in patients with colorectal cancer undergoing radical surgery","authors":"Jeng-Fu You ,&nbsp;Cheng-Chi Lee ,&nbsp;Yun-Shien Lee ,&nbsp;Yih-Jong Chern ,&nbsp;Chun-Kai Liao ,&nbsp;Hung-Chih Hsu","doi":"10.1016/j.tranon.2024.102198","DOIUrl":"10.1016/j.tranon.2024.102198","url":null,"abstract":"<div><h3>Introduction</h3><div>Natural killer (NK) cell activity (NKA) is downregulated in patients with colorectal cancer (CRC), and its dysfunction is possibly associated with increased risk of recurrence. However, its role in prognosis of CRC remains unclear. Prior research has shown that surgical stress can suppress NKA. This study explores the relationship between NK cell/NKA and clinicopathological factors during the perioperative period in patients with CRC.</div></div><div><h3>Methods</h3><div>We prospectively enrolled 45 patients with CRC. Venous blood samples were collected preoperatively and on postoperative day 3 (POD3) and 30 (POD30). NKA was assessed by measuring the plasma levels of NK cell-secreted IFN-γ.</div></div><div><h3>Results</h3><div>NKA was significantly reduced on POD3 compared with baseline levels before surgery but showed significant recovery by POD30. NKA on POD30 was considerably higher in patients with advanced disease stages or one or more high-risk preoperative factors. Additionally, a higher NKA recovery in patients with advanced stage exhibited improved recurrence-free survival (RFS) and progression-free survival (PFS) (hazards ratio (HR): 0.2442). Furthermore, an increased percentage of CD56^bright NK cells and a higher CD56^bright/CD56^dim NK cell ratio postoperatively on POD30 were associated with better RFS/PFS (HR: 0.2732, <em>P</em> = 0.0433 and HR: 0.2193, <em>P</em> = 0.024, respectively).</div></div><div><h3>Conclusions</h3><div>Our findings indicate that a notable postoperative increase in CD56^bright NK cells on POD30, both in percentage and ratio, correlates with a more favorable prognosis in CRC patients. Additionally, higher recovery rates of NKA in patients with advanced stages may offer potential applications in risk stratification and the development of treatment strategies for CRC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102198"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-based deep learning and radiomics for predicting the efficacy of PD-1 inhibitor combined with induction chemotherapy in advanced nasopharyngeal carcinoma: A prospective cohort study","authors":"Yiru Wang ,&nbsp;Fuli Chen ,&nbsp;Zhechen Ouyang ,&nbsp;Siyi He ,&nbsp;Xinling Qin ,&nbsp;Xian Liang ,&nbsp;Weimei Huang ,&nbsp;Rensheng Wang ,&nbsp;Kai Hu","doi":"10.1016/j.tranon.2024.102245","DOIUrl":"10.1016/j.tranon.2024.102245","url":null,"abstract":"<div><h3>Background</h3><div>An increasing number of nasopharyngeal carcinoma (NPC) patients benefit from immunotherapy with chemotherapy as an induction treatment. Currently, there isn't a reliable method to assess the efficacy of this regimen, which hinders informed decision-making for follow-up care.</div></div><div><h3>Aim</h3><div>To establish and evaluate a model for predicting the efficacy of programmed death-1 (PD-1) inhibitor combined with GP (gemcitabine and cisplatin) induction chemotherapy based on deep learning features (DLFs) and radiomic features.</div></div><div><h3>Methods</h3><div>Ninety-nine patients diagnosed with advanced NPC were enrolled and randomly divided into training set and test set in a 7:3 ratio. From MRI scans, DLFs and conventional radiomic characteristics were recovered. The random forest algorithm was employed to identify the most valuable features. A prediction model was then created using these radiomic characteristics and DLFs to determine the effectiveness of PD-1 inhibitor combined with GP chemotherapy. The model's performance was assessed using Receiver Operating Characteristic (ROC) curve analysis, area under the curve (AUC), accuracy (ACC), and negative predictive value (NPV).</div></div><div><h3>Results</h3><div>Twenty-one prediction models were constructed. The Tf_Radiomics+Resnet101 model, which combines radiomic features and DLFs, demonstrated the best performance. The model's AUC, ACC, and NPV values in the training and test sets were 0.936 (95%CI: 0.827–1.0), 0.9, and 0.923, respectively.</div></div><div><h3>Conclusion</h3><div>The Tf_Radiomics+Resnet101 model, based on MRI and Resnet101 deep learning, shows a high ability to predict the clinically complete response (cCR) efficacy of PD-1 inhibitor combined with GP in advanced NPC. This model can significantly enhance the treatment management of patients with advanced NPC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"52 ","pages":"Article 102245"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}