{"title":"Dynamics of tumor in situ fluid circulating tumor DNA in recurrent glioblastomas forecasts treatment efficacy of immune checkpoint blockade coupled with low-dose bevacizumab.","authors":"Dayang Wang, Jiubing Zhang, Chaojie Bu, Guanzheng Liu, Guangzhong Guo, Ziyue Zhang, Guangming Lv, Zhiyuan Sheng, Zhaoyue Yan, Yvshuai Gao, Meiyun Wang, Gang Liu, Ruijiao Zhao, Tianxiao Li, Chunxiao Ma, Xingyao Bu","doi":"10.1007/s00432-024-05997-8","DOIUrl":"10.1007/s00432-024-05997-8","url":null,"abstract":"<p><strong>Purpose: </strong>Immune checkpoint blockade (ICB) therapies have shown efficacy in various tumors, but long-term responses in glioblastoma are less than 10%. Quantifying tumor in situ fluid circulating tumor DNA (TISF-ctDNA) and therapeutic dynamics may enable real-time GBM disease burden evaluation. This study explores the potential of tumor in situ fluid circulating tumor DNA (TISF-ctDNA) dynamics in predicting treatment efficacy.</p><p><strong>Methods: </strong>TISF and peripheral blood samples were collected from patients with recurrent glioblastoma (rGBM) undergoing tislelizumab (a programmed death 1 inhibitor) combined with low-dose bevacizumab (an anti-vascular endothelial growth factor antibody) treatment before and during each immunotherapy cycle. Biomarkers evaluated included TISF-ctDNA, measured using Next Generation Sequencing (NGS), and host inflammation markers such as the platelet-to-lymphocyte ratio (PLR).</p><p><strong>Results: </strong>All 32 patients received tislelizumab plus low-dose bevacizumab regularly. The median progression-free survival (PFS) was 4.0 months, and overall survival (OS) was 22.3 months. An analysis of 19 patients with continuous evaluable TISF showed baseline TISF-ctDNA abundance did not correlate with OS (p = 0.23) or PFS (p = 0.23). However, a change in TISF-ctDNA maximal Somatic Variant Allelic Frequency (MVAF) after six treatment cycles predicted both PFS (p = 0.02) and OS (p < 0.0001). Lower baseline PLR also correlated with better survival outcomes.</p><p><strong>Conclusion: </strong>The combination of tislelizumab and low-dose bevacizumab therapy appears to be effective in extending both OS and PFS in rGBM patients. Continuous TISF-ctDNA testing shows potential utility in complementing radiological monitoring. The temporal change pattern of TISF MVAF is more predictive of immunotherapy response than imaging. PLR before immunotherapy can screen patients likely to benefit from tislelizumab plus low-dose bevacizumab therapy.</p><p><strong>Trial registration: </strong>The trial registration number: NCT05502991; Date of registration: 2022-08-14.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466188","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 impact of clonal hematopoiesis mutations at complete molecular remission in acute myeloid leukemia with NPM1 mutation.","authors":"Linlin Wang, Mingkai Shu, Zhibo Zhang, Xueqing Dou, Xiaoyu Xu, Yanan Ma, Lijun Wen, Xiaofei Yang, Suning Chen","doi":"10.1007/s00432-024-05999-6","DOIUrl":"10.1007/s00432-024-05999-6","url":null,"abstract":"<p><p>The prognostic impact of clonal hematopoiesis (CH) in complete molecular remission (CMR) in acute myeloid leukemia (AML) remains controversial. Here, we explored the prognosis of CH-related gene mutations (CH-mutation) at CMR in patients with AML with NPM1 mutation (NPM1c AML). Ninety-one patients with de novo NPM1c AML were included between June 2018 and June 2023, including 32 patients with CH-related mutation at CMR and 59 patients without. A cutoff of ≥ 2.0% for variant allele frequency (VAF) of residual mutations was used to define CH-mutation at CMR. Thirty-two patients with CH-mutation at CMR had a greater median age and higher white blood cell (WBC) counts than those without (median age, 50.5 and 45 years, respectively; p = 0.028 and WBC count: 34.5 and 10 × 10<sup>9</sup>/l, respectively; p = 0.004). The incidence of DNMT3A and TET2 mutations before treatment was higher in the group with CH-mutations at CMR compared to the one without (71.9% vs. 13.6%, and 21.9% vs. 6.8%, respectively). Notably, all patients did not carry any CH of oncogenic potential (CHOP)-like mutations in CMR. There was no significant difference in event-free survival (EFS) or overall survival (OS) between the patients with and without CH-mutations at CMR or between the patients without allogeneic hematopoietic stem cell transplantation (allo-HSCT) of the two groups. In conclusion, our results suggested that CH-mutations probably did not have prognostic significance in patients with NPM1c AML who achieved CMR, and may be inappropriately for MRD monitoring.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466196","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}
Yu Xiaojian, Qu Zhanbo, Chu Jian, Wang Zefeng, Liu Jian, Liu Jin, Pan Yuefen, Han Shuwen
{"title":"Deep learning application in prediction of cancer molecular alterations based on pathological images: a bibliographic analysis via CiteSpace.","authors":"Yu Xiaojian, Qu Zhanbo, Chu Jian, Wang Zefeng, Liu Jian, Liu Jin, Pan Yuefen, Han Shuwen","doi":"10.1007/s00432-024-05992-z","DOIUrl":"10.1007/s00432-024-05992-z","url":null,"abstract":"<p><strong>Background: </strong>The advancements in artificial intelligence (AI) technology for image recognition were propelling molecular pathology research into a new era.</p><p><strong>Objective: </strong>To summarize the hot spots and research trends in the field of molecular pathology image recognition.</p><p><strong>Methods: </strong>Relevant articles from January 1st, 2010, to August 25th, 2023, were retrieved from the Web of Science Core Collection. Subsequently, CiteSpace was employed for bibliometric and visual analysis, generating diverse network diagrams illustrating keywords, highly cited references, hot topics, and research trends.</p><p><strong>Results: </strong>A total of 110 relevant articles were extracted from a pool of 10,205 articles. The overall publication count exhibited a rising trend each year. The leading contributors in terms of institutions, countries, and authors were Maastricht University (11 articles), the United States (38 articles), and Kather Jacob Nicholas (9 articles), respectively. Half of the top ten research institutions, based on publication volume, were affiliated with Germany. The most frequently cited article was authored by Nicolas Coudray et al. accumulating 703 citations. The keyword \"Deep learning\" had the highest frequency in 2019. Notably, the highlighted keywords from 2022 to 2023 included \"microsatellite instability\", and there were 21 articles focusing on utilizing algorithms to recognize microsatellite instability (MSI) in colorectal cancer (CRC) pathological images.</p><p><strong>Conclusion: </strong>The use of DL is expected to provide a new strategy to effectively solve the current problem of time-consuming and expensive molecular pathology detection. Therefore, further research is needed to address issues, such as data quality and standardization, model interpretability, and resource and infrastructure requirements.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466186","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}
Nicole Ernstmann, Hannah Nakata, Lina Heier, Christian Heuser, Marc Dohmen, Rebecca Bremen, Franziska Geiser, Steffen Holsteg, Andre Karger, Anja Viehmann, Manuela Brüne, Andrea Icks, Burkhard Haastert, Tim H Brümmendorf, Andrea Petermann-Meyer
{"title":"Feasibility of a complex psychosocial intervention for families with parental cancer: acceptability, suitability, implementability, and perceived support.","authors":"Nicole Ernstmann, Hannah Nakata, Lina Heier, Christian Heuser, Marc Dohmen, Rebecca Bremen, Franziska Geiser, Steffen Holsteg, Andre Karger, Anja Viehmann, Manuela Brüne, Andrea Icks, Burkhard Haastert, Tim H Brümmendorf, Andrea Petermann-Meyer","doi":"10.1007/s00432-024-05946-5","DOIUrl":"10.1007/s00432-024-05946-5","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess the feasibility of a comprehensive psychosocial intervention for families coping with parental cancer.</p><p><strong>Methods: </strong>A quasi-experimental trial with intervention and control group, employing a mixed-methods approach, was conducted. A total of 472 families affected by parental cancer participated. The feasibility of the intervention was evaluated based on study monitoring measures (on-site visits, team supervision meeting observations, case conference observations, best practice workshops, coordinating information exchange between intervention sites, and reviewing intervention documentation), process evaluation (semi-structured interviews, focus group discussion) and survey data. Data analysis involved thematic coding and descriptive statistics.</p><p><strong>Results: </strong>The intervention was well-received by the participating families, with a high degree of acceptance observed. The feasibility of the intervention was found to be associated with specific dynamics within each family system and the motivation of the family members. The success of the intervention was described as dependent on the family-centered arrangement of the encounters, including factors such as frequency, duration, and mode, which greatly influenced its overall acceptability.</p><p><strong>Conclusion: </strong>The family-scout intervention demonstrates its feasibility as an effective intervention to reduce the burden experienced by families coping with parental cancer. Psychosocial oncology services should continue to develop and implement family-centered interventions to offer support to families during their cancer journey.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT04186923. Retrospectively registered on 4 December 2019.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466192","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}
David Heimdörfer, Nastasiia Artamonova, Zoran Culig, Isabel Heidegger
{"title":"Unraveling molecular characteristics and tumor microenvironment dynamics of neuroendocrine prostate cancer.","authors":"David Heimdörfer, Nastasiia Artamonova, Zoran Culig, Isabel Heidegger","doi":"10.1007/s00432-024-05983-0","DOIUrl":"10.1007/s00432-024-05983-0","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the most prevalent malignancy and the second leading cause of cancer-related deaths among men. While adenocarcinoma of the prostate (adeno-PCa) is well-characterized, neuroendocrine prostate cancer (NEPC) remains poorly understood. Generally, NEPC is a rare but highly aggressive histological variant, however its limited patho-physiological understanding leads to insufficient treatment options associated with low survival rates for NEPC patients. Current treatments for NEPC, including platinum-based therapies, offer some efficacy, but there is a significant need for more targeted approaches. This review summarizes the molecular characteristics of NEPC in contrast to adeno-PCa, providing a comprehensive comparison. A significant portion of the discussion is dedicated to the tumor microenvironment (TME), which has recently been identified as a key factor in tumor progression. The TME includes various cells, signaling molecules, and the extracellular matrix surrounding the tumor, all of which play critical roles in cancer development and response to treatment. Understanding the TME's influence on NEPC could uncover new avenues for innovative treatment strategies, potentially improving outcomes for patients with this challenging variant of PCa.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466198","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}
Hailong Xie, Mingjiang Dan, Yi Cen, Jing Ning, Chong Sun, Guangbin Zhu, Shourui Feng, Haiyan Wang, Jinxian Pu
{"title":"AR expression-independent XRCC3 mediates DNA damage-induced p53/Bax signaling pathway activation against prostate cancer.","authors":"Hailong Xie, Mingjiang Dan, Yi Cen, Jing Ning, Chong Sun, Guangbin Zhu, Shourui Feng, Haiyan Wang, Jinxian Pu","doi":"10.1007/s00432-024-05989-8","DOIUrl":"10.1007/s00432-024-05989-8","url":null,"abstract":"<p><strong>Background: </strong>Androgen deprivation therapy (ADT) resistance is closely associated with altered AR status. Aberrant AR expression is critical for the induction of ADT resistance, necessitating the identification of an anti-PCa target independent of AR expression.</p><p><strong>Methods: </strong>Transcriptomic data and clinical information of PRAD were obtained from TCGA database. Genes with PCa-related and AR expression-independent were screened by bioinformatics, and characterized by PPI and GO functional enrichment analyses. Candidate genes were locked by co-expression correlation and disease-free survival (DFS) analyses. A prognostic gene set was established using LASSO Cox regression algorithm. Cox proportional risk regression was performed to identify a key prognostic gene. Expression of the target protein in PCa tissues was verified by The Human Protein Atlas database. In vitro validation of cellular function and molecular mechanism by knockdown and overexpression of the target gene.</p><p><strong>Results: </strong>Two AR expression-independent genes (SLC43A1 and XRCC3) were available for the optimal prognostic model. This gene set effectively predicted PRAD patients' DFS at 1-, 3- and 5-year, where XRCC3 and tumor (T) stage were independent risk factors. XRCC3 was higher expressed in PRAD patients with T3-T4 stages and accompanied by poorer DFS. IHC staining also validated its higher expression in high-risk PCa tissues. In vitro experiments demonstrated that silencing XRCC3 significantly inhibited 22Rv1 and DU145 cell proliferation, migration and invasion, while promoted apoptosis. Further, silencing XRCC3 promoted DNA damage-induced p53/Bax signaling pathway activation, which was absent with overexpression.</p><p><strong>Conclusion: </strong>Silencing XRCC3 exerts anti-PCa effects by promoting DNA damage-induced p53/Bax signaling pathway activation in an AR expression-independent manner.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466184","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}
Hang Zhou, Yong Jiang, Yang Zhou, Zhao Zhang, Shaoyin Li
{"title":"miR-182-5p promotes the proliferation and invasion of hilar cholangiocarcinoma cells by inhibiting FBXW7.","authors":"Hang Zhou, Yong Jiang, Yang Zhou, Zhao Zhang, Shaoyin Li","doi":"10.1007/s00432-024-05961-6","DOIUrl":"10.1007/s00432-024-05961-6","url":null,"abstract":"<p><strong>Background: </strong>Hilar cholangiocarcinoma (HCCA) is a common type of cholangiocarcinoma (CHOL) that originates from the right and/or left hepatic duct near the biliary tract confluence. The objective of this study is to investigate the impact of miR-182-5p on the proliferation and invasion of HCCA cells and identify a potential target for HCCA treatment.</p><p><strong>Methods: </strong>HCCA tissues were collected and HCCA cells were cultured. miR-182-5p and F-box and WD repeat domain containing 7 (FBXW7) were detected. After transfection of miR-182-5p inhibitor into HCCA cells, cell proliferation and invasion were detected by cell counting 8-kit and Transwell assay. FBXW7 expression was detected by Western blot. The targeted relationship between miR-182-5p and FBXW7 3'UTR was verified by dual-luciferase report assay. si-FBXW7 and miR-182-5p inhibitor were transfected into cells for combined experiments. HCCA cells with lowly-expressed miR-182-5p were injected into nude mice to establish the xenograft tumor model, and subsequent observations were made on tumor growth and gene expression changes.</p><p><strong>Results: </strong>miR-182-5p exhibited high expression levels in both HCCA tissues and cell lines. Inhibiting miR-182-5p effectively suppressed the proliferation and migration of HCCA cells. miR-182-5p bounded to FBXW7 3 'UTR and inhibited FBWX7 expression. Suppressing FBXW7 expression partially reversed the inhibitory effect of miR-182-5p inhibitor on HCCA cell proliferation and invasion. Silencing miR-182-5p could inhibit the HCCA growth in vivo.</p><p><strong>Conclusion: </strong>miR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466193","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}
Gerd Jomrich, Winny Yan, Dagmar Kollmann, Ivan Kristo, Daniel Winkler, Hannah Puhr, Aysegül Lhan-Mutlu, Marlene Hollenstein, Reza Asari, Sebastian F Schoppmann
{"title":"Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma.","authors":"Gerd Jomrich, Winny Yan, Dagmar Kollmann, Ivan Kristo, Daniel Winkler, Hannah Puhr, Aysegül Lhan-Mutlu, Marlene Hollenstein, Reza Asari, Sebastian F Schoppmann","doi":"10.1007/s00432-024-05976-z","DOIUrl":"10.1007/s00432-024-05976-z","url":null,"abstract":"<p><strong>Purpose: </strong>Serum fibrinogen and albumin play important roles in systemic inflammation and are implicated in tumor progression. The fibrinogen-to-albumin ratio (FAR) has shown a prognostic impact in several malignancies. This study aims to assess the prognostic value of the pretherapeutic FAR in patients with adenocarcinoma of the gastroesophageal junction (AEG) who underwent upfront resection.</p><p><strong>Methods: </strong>Consecutive patients who underwent surgical resection at the Department of Surgery at the Medical University of Vienna between 1992 and 2014 were included into this study. Optimal cut-off values were determined with the receiver-operating characteristic (ROC) curve, uni- and multivariate analyzes were calculated by the Cox proportional hazard regression model for overall survival (OS).</p><p><strong>Results: </strong>Among 135 included patients, the majority were male (79.26%), with a mean age of 66.53 years. Elevated FAR correlated significantly (p = 0.002) with shorter OS in univariate analysis, also confirmed as independent prognostic factor (p = 0.005) in multivariable analysis. The ROC curve of FAR (AUC = 0.744) outperformed fibrinogen (AUC = 0.738) and albumin (AUC = 0.378) in predicting OS for AEG patients.</p><p><strong>Conclusion: </strong>The FAR serves as an independent prognostic factor for OS in patients undergoing primarily resection for AEG. Given its routine availability and ease of calculation, FAR could help in diagnosis and treatment selection for AEG patients. Further validation studies are warranted to confirm these findings conclusively.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466189","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":"Predicting chemotherapy-induced thrombotoxicity by NARX neural networks and transfer learning.","authors":"Marie Steinacker, Yuri Kheifetz, Markus Scholz","doi":"10.1007/s00432-024-05985-y","DOIUrl":"10.1007/s00432-024-05985-y","url":null,"abstract":"<p><strong>Background: </strong>Thrombocytopenia is a common side effect of cytotoxic chemotherapies, which is often dose-limiting. Predicting an individual's risk is of high clinical importance, as otherwise, a small subgroup of patients limits dosages for the overall population for safety reasons.</p><p><strong>Methods: </strong>We aim to predict individual platelet dynamics using non-linear auto-regressive networks with exogenous inputs (NARX). We consider different architectures of the NARX networks, namely feed-forward networks (FNN) and gated recurrent units (GRU). To cope with the relative sparsity of individual patient data, we employ transfer learning (TL) approaches based on a semi-mechanistic model of hematotoxicity. We use a large data set of patients with high-grade non-Hodgkin's lymphoma to learn the respective models on an individual scale and to compare prediction performances with that of the semi-mechanistic model.</p><p><strong>Results: </strong>Of the examined network models, the NARX with GRU architecture performs best. In comparison to the semi-mechanistic model, the network model can result in a substantial improvement of prediction accuracy for patients with irregular dynamics, given well-spaced measurements. TL improves individual prediction performances.</p><p><strong>Conclusion: </strong>NARX networks can be utilized to predict an individual's thrombotoxic response to cytotoxic chemotherapy treatment. For reasonable model learning, we recommend at least three well-spaced measurements per cycle: at baseline, during the nadir phase and during the recovery phase. We aim at generalizing our approach to other treatment scenarios and blood lineages in the future.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466195","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}
Qingge Gong, La Zhang, Jiao Guo, Wei Zhao, Baoyong Zhou, Changhong Yang, Ning Jiang
{"title":"FBXO family genes promotes hepatocellular carcinoma via ubiquitination of p53.","authors":"Qingge Gong, La Zhang, Jiao Guo, Wei Zhao, Baoyong Zhou, Changhong Yang, Ning Jiang","doi":"10.1007/s00432-024-05948-3","DOIUrl":"10.1007/s00432-024-05948-3","url":null,"abstract":"<p><p>FBXO protein family plays an essential role in the ubiquitination process acting as E3 ligases, which may contribute to the progression of cancers. However, the molecular functions of FBXOs in hepatocellular carcinoma (HCC) remain incompletely understood. Here, we investigated the overlapping genes between the FBXOs and differentially expressed genes (DEGs) of HCC identified by utilizing The Cancer Genome Atlas (TCGA) dataset, then, a prognostic model with effective predictive capacity was constructed based on the uni-cox and LASSO regression analyses. To elucidate the underlying mechanism of the FBXO model genes, KEGG analysis was carried out. Drug metabolism-cytochrome P450 and retinol metabolism were revealed as the potential pathway, which Increased the credibility of subsequent drug prediction research. Meanwhile, patients divided by the prognostic model showed a different immune infiltrating status and we also found FBXO model genes may ubiquitinate P53, inducing TP53 more prone to mutations, thereby promoting the occurrence and development of tumors. Consistent with these findings, the result of immunohistochemistry (IHC) validated an elevated expression of these model genes in HCC tissues than in the adjacent tissues. The primary aim of this investigation is to formulate a prognostic model while exploring the underlying mechanisms associated with FBXO genes in HCC. These findings offer initial research perspectives on the involvement of FBXO genes in HCC and contribute to the discovery of dependable biomarkers for the management, prognostication, and early detection of HCC in patients.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466191","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}