HPV status in a subset of HNSCC is linked with distinct treatment outcomes. Present investigation aims to elucidate the distinct clinicopathological features of HPV-positive and HPV-negative HNSCC and investigate their association with the HNSCC patient survival. The total RNA of exosomes from HPV-positive (93VU147T) and HPV-negative (OCT-1) HNSCC cells was isolated, and the transcripts were estimated using Illumina HiSeq X. The expression of altered transcripts and their clinical relevance were further analyzed using publicly available cancer transcriptome data from The Cancer Genome Atlas (TCGA). Transcriptomic analyses identified 3785 differentially exported transcripts (DETs) in HPV-positive exosomes compared to HPV-negative exosomes. DETs that regulate the protein machinery, cellular redox potential, and various neurological disorder-related pathways were over-represented in HPV-positive exosomes. TCGA database revealed the clinical relevance of altered transcripts. Among commonly exported abundant transcripts, SGK1 and MAD1L1 showed high expression, which has been correlated with poor survival in HNSCC patients. In the top 20 DETs of HPV-negative exosomes, high expression of FADS3, SGK3, and TESK2 correlated with poor survival of the HNSCC patients in the TCGA database. Overall, our study demonstrates that HPV-positive and HPV-negative cells’ exosomes carried differential transcripts cargo that may be related to pathways associated with neurological disorders. Additionally, the altered transcripts identified have clinical relevance, correlating with patient survival in HNSCC, thereby highlighting their potential as biomarkers and as therapeutic targets.
{"title":"Exosomal transcript cargo and functional correlation with HNSCC patients’ survival","authors":"Joni Yadav, Apoorva Chaudhary, Tanya Tripathi, Divya Janjua, Udit Joshi, Nikita Aggarwal, Arun Chhokar, Chetkar Chandra Keshavam, Anna Senrung, Alok Chandra Bharti","doi":"10.1186/s12885-024-12759-9","DOIUrl":"https://doi.org/10.1186/s12885-024-12759-9","url":null,"abstract":"HPV status in a subset of HNSCC is linked with distinct treatment outcomes. Present investigation aims to elucidate the distinct clinicopathological features of HPV-positive and HPV-negative HNSCC and investigate their association with the HNSCC patient survival. The total RNA of exosomes from HPV-positive (93VU147T) and HPV-negative (OCT-1) HNSCC cells was isolated, and the transcripts were estimated using Illumina HiSeq X. The expression of altered transcripts and their clinical relevance were further analyzed using publicly available cancer transcriptome data from The Cancer Genome Atlas (TCGA). Transcriptomic analyses identified 3785 differentially exported transcripts (DETs) in HPV-positive exosomes compared to HPV-negative exosomes. DETs that regulate the protein machinery, cellular redox potential, and various neurological disorder-related pathways were over-represented in HPV-positive exosomes. TCGA database revealed the clinical relevance of altered transcripts. Among commonly exported abundant transcripts, SGK1 and MAD1L1 showed high expression, which has been correlated with poor survival in HNSCC patients. In the top 20 DETs of HPV-negative exosomes, high expression of FADS3, SGK3, and TESK2 correlated with poor survival of the HNSCC patients in the TCGA database. Overall, our study demonstrates that HPV-positive and HPV-negative cells’ exosomes carried differential transcripts cargo that may be related to pathways associated with neurological disorders. Additionally, the altered transcripts identified have clinical relevance, correlating with patient survival in HNSCC, thereby highlighting their potential as biomarkers and as therapeutic targets.\u0000","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1186/s12885-024-12892-5
Qingyuan Zhang, Zhonghua Wang, Wei Yao, Shufang Wang, Gaochong Zhang, Jianmin Chen, Qingsong Hou, Simon Li, Hongsheng Li, Changsheng Ye, Tao Sun, Hongjian Yang, Zhendong Chen, Zhihong Wang, Xiaoan Liu, Cuizhi Geng, Xingrui Li, Jin Zhang, Hong Zheng, Zhimin Shao
F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. ClinicalTrials.gov: NCT04174599, on 22/11/2019.
{"title":"A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer","authors":"Qingyuan Zhang, Zhonghua Wang, Wei Yao, Shufang Wang, Gaochong Zhang, Jianmin Chen, Qingsong Hou, Simon Li, Hongsheng Li, Changsheng Ye, Tao Sun, Hongjian Yang, Zhendong Chen, Zhihong Wang, Xiaoan Liu, Cuizhi Geng, Xingrui Li, Jin Zhang, Hong Zheng, Zhimin Shao","doi":"10.1186/s12885-024-12892-5","DOIUrl":"https://doi.org/10.1186/s12885-024-12892-5","url":null,"abstract":"F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. ClinicalTrials.gov: NCT04174599, on 22/11/2019.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1186/s12885-024-12890-7
Jiankun Zhu, Shilin Zhi, Jintao Zeng, Shengning Zhou, Yong Ji, Fanghai Han
Colorectal cancer ranks among the most prevalent malignancies globally. Accurate prediction of metachronous liver metastasis is crucial for optimizing postoperative management. Tripartite motif-containing protein 27 (TRIM27), an E3 ubiquitin ligase, is implicated in diverse cellular functions and tumorigenesis. This study aimed to develop and validate a TRIM27-based nomogram for prognostication in colorectal cancer patients. Transcriptome sequencing of five paired tumor and normal tissue samples identified TRIM27 as a potential prognostic biomarker. Immunohistochemistry was employed to assess TRIM27 expression in colorectal cancer cohorts from two institutions. TRIM27 expression correlated significantly with both the prognosis of colorectal cancer patients and the occurrence of metachronous liver metastasis. A nomogram incorporating TRIM27 and clinical factors was constructed and demonstrated robust predictive accuracy in an independent validation cohort. The TRIM27-based nomogram is a valuable prognostic tool for predicting prognosis and metachronous liver metastasis in colorectal cancer patients, aiding in personalized treatment decisions.
{"title":"Development and validation of a TRIM27-based nomogram for predicting metachronous liver metastasis and prognosis in postoperative colorectal cancer patients","authors":"Jiankun Zhu, Shilin Zhi, Jintao Zeng, Shengning Zhou, Yong Ji, Fanghai Han","doi":"10.1186/s12885-024-12890-7","DOIUrl":"https://doi.org/10.1186/s12885-024-12890-7","url":null,"abstract":"Colorectal cancer ranks among the most prevalent malignancies globally. Accurate prediction of metachronous liver metastasis is crucial for optimizing postoperative management. Tripartite motif-containing protein 27 (TRIM27), an E3 ubiquitin ligase, is implicated in diverse cellular functions and tumorigenesis. This study aimed to develop and validate a TRIM27-based nomogram for prognostication in colorectal cancer patients. Transcriptome sequencing of five paired tumor and normal tissue samples identified TRIM27 as a potential prognostic biomarker. Immunohistochemistry was employed to assess TRIM27 expression in colorectal cancer cohorts from two institutions. TRIM27 expression correlated significantly with both the prognosis of colorectal cancer patients and the occurrence of metachronous liver metastasis. A nomogram incorporating TRIM27 and clinical factors was constructed and demonstrated robust predictive accuracy in an independent validation cohort. The TRIM27-based nomogram is a valuable prognostic tool for predicting prognosis and metachronous liver metastasis in colorectal cancer patients, aiding in personalized treatment decisions.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12885-024-12911-5
Shengshan Xu, Xiguang Chen, Haoxuan Ying, Jiarong Chen, Min Ye, Zhichao Lin, Xin Zhang, Tao Shen, Zumei Li, Youbin Zheng, Dongxi Zhang, Yongwen Ke, Zhuowen Chen, Zhuming Lu
Lung adenocarcinoma (LUAD) significantly contributes to cancer-related mortality worldwide. The heterogeneity of the tumor immune microenvironment in LUAD results in varied prognoses and responses to immunotherapy among patients. Consequently, a clinical stratification algorithm is necessary and inevitable to effectively differentiate molecular features and tumor microenvironments, facilitating personalized treatment approaches. We constructed a comprehensive single-cell transcriptional atlas using single-cell RNA sequencing data to reveal the cellular diversity of malignant epithelial cells of LUAD and identified a novel signature through a computational framework coupled with 10 machine learning algorithms. Our study further investigates the immunological characteristics and therapeutic responses associated with this prognostic signature and validates the predictive efficacy of the model across multiple independent cohorts. We developed a six-gene prognostic model (MYO1E, FEN1, NMI, ZNF506, ALDOA, and MLLT6) using the TCGA-LUAD dataset, categorizing patients into high- and low-risk groups. This model demonstrates robust performance in predicting survival across various LUAD cohorts. We observed distinct molecular patterns and biological processes in different risk groups. Additionally, analysis of two immunotherapy cohorts (N = 317) showed that patients with a high-risk signature responded more favorably to immunotherapy compared to those in the low-risk group. Experimental validation further confirmed that MYO1E enhances the proliferation and migration of LUAD cells. We have identified malignant cell-associated ligand–receptor subtypes in LUAD cells and developed a robust prognostic signature by thoroughly analyzing genomic, transcriptomic, and immunologic data. This study presents a novel method to assess the prognosis of patients with LUAD and provides insights into developing more effective immunotherapies.
{"title":"Multi‑omics identification of a signature based on malignant cell-associated ligand–receptor genes for lung adenocarcinoma","authors":"Shengshan Xu, Xiguang Chen, Haoxuan Ying, Jiarong Chen, Min Ye, Zhichao Lin, Xin Zhang, Tao Shen, Zumei Li, Youbin Zheng, Dongxi Zhang, Yongwen Ke, Zhuowen Chen, Zhuming Lu","doi":"10.1186/s12885-024-12911-5","DOIUrl":"https://doi.org/10.1186/s12885-024-12911-5","url":null,"abstract":"Lung adenocarcinoma (LUAD) significantly contributes to cancer-related mortality worldwide. The heterogeneity of the tumor immune microenvironment in LUAD results in varied prognoses and responses to immunotherapy among patients. Consequently, a clinical stratification algorithm is necessary and inevitable to effectively differentiate molecular features and tumor microenvironments, facilitating personalized treatment approaches. We constructed a comprehensive single-cell transcriptional atlas using single-cell RNA sequencing data to reveal the cellular diversity of malignant epithelial cells of LUAD and identified a novel signature through a computational framework coupled with 10 machine learning algorithms. Our study further investigates the immunological characteristics and therapeutic responses associated with this prognostic signature and validates the predictive efficacy of the model across multiple independent cohorts. We developed a six-gene prognostic model (MYO1E, FEN1, NMI, ZNF506, ALDOA, and MLLT6) using the TCGA-LUAD dataset, categorizing patients into high- and low-risk groups. This model demonstrates robust performance in predicting survival across various LUAD cohorts. We observed distinct molecular patterns and biological processes in different risk groups. Additionally, analysis of two immunotherapy cohorts (N = 317) showed that patients with a high-risk signature responded more favorably to immunotherapy compared to those in the low-risk group. Experimental validation further confirmed that MYO1E enhances the proliferation and migration of LUAD cells. We have identified malignant cell-associated ligand–receptor subtypes in LUAD cells and developed a robust prognostic signature by thoroughly analyzing genomic, transcriptomic, and immunologic data. This study presents a novel method to assess the prognosis of patients with LUAD and provides insights into developing more effective immunotherapies.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12885-024-12909-z
Eya Khadhraoui, Leon Schmidt, Stefan Klebingat, Roland Schwab, Silvia Hernández-Durán, Georg Gihr, Harald Paukisch, Klaus-Peter Stein, Daniel Behme, Sebastian Johannes Müller
MR perfusion is a standard marker to distinguish progression and therapy-associated changes after surgery and radiochemotherapy for glioblastoma. TRAMs (Treatment Response Assessment Maps) were introduced, which are intended to facilitate the differentiation of vital tumor cells and radiation necrosis by means of late (20–90 min) contrast clearance and enhancement. The differences of MR perfusion and late-enhancement are not fully understood yet. We have implemented and established a fully automated creation of rapid wash-out (15–20 min interval) maps in our clinic. We included patients with glioblastoma, CNS lymphoma or brain metastases who underwent our MR protocol with MR perfusion and rapid wash-out between 01/01/2024 and 30/06/2024. Since both wash-out and hyperperfusion are intended to depict the active tumor area, this study involves a quantitative and qualitative comparison of both methods. For this purpose, we volumetrically measured rCBV (relative cerebral blood volume) maps and rapid wash-out maps separately (two raters). Additionally, we rated the agreement between both maps on a Likert scale (0–10). Thirty-two patients were included in the study: 15 with glioblastoma, 7 with CNS lymphomas and 10 with brain metastasis. We calculated 36 rapid wash-out maps (9 initial diagnosis, 27 follow-up). Visual agreement of MR perfusion with rapid wash-out by rating were found in 44 ± 40% for initial diagnosis, and 75 ± 31% for follow-up. We found a strong correlation (Pearson coefficient 0.92, p < 0.001) between the measured volumes of MR perfusion and rapid wash-out. The measured volumes of MR perfusion and rapid wash-out did not differ significantly. Small lesions were often not detected by MR perfusion. Nevertheless, the measured volumes showed no significant differences in this small cohort. Rapid wash-out calculation is a simple tool that provides new information and, when used in conjunction with MR perfusion, may increase diagnostic accuracy. The method shows promising results, particularly in the evaluation of small lesions.
{"title":"Comparison of a new MR rapid wash-out map with MR perfusion in brain tumors","authors":"Eya Khadhraoui, Leon Schmidt, Stefan Klebingat, Roland Schwab, Silvia Hernández-Durán, Georg Gihr, Harald Paukisch, Klaus-Peter Stein, Daniel Behme, Sebastian Johannes Müller","doi":"10.1186/s12885-024-12909-z","DOIUrl":"https://doi.org/10.1186/s12885-024-12909-z","url":null,"abstract":"MR perfusion is a standard marker to distinguish progression and therapy-associated changes after surgery and radiochemotherapy for glioblastoma. TRAMs (Treatment Response Assessment Maps) were introduced, which are intended to facilitate the differentiation of vital tumor cells and radiation necrosis by means of late (20–90 min) contrast clearance and enhancement. The differences of MR perfusion and late-enhancement are not fully understood yet. We have implemented and established a fully automated creation of rapid wash-out (15–20 min interval) maps in our clinic. We included patients with glioblastoma, CNS lymphoma or brain metastases who underwent our MR protocol with MR perfusion and rapid wash-out between 01/01/2024 and 30/06/2024. Since both wash-out and hyperperfusion are intended to depict the active tumor area, this study involves a quantitative and qualitative comparison of both methods. For this purpose, we volumetrically measured rCBV (relative cerebral blood volume) maps and rapid wash-out maps separately (two raters). Additionally, we rated the agreement between both maps on a Likert scale (0–10). Thirty-two patients were included in the study: 15 with glioblastoma, 7 with CNS lymphomas and 10 with brain metastasis. We calculated 36 rapid wash-out maps (9 initial diagnosis, 27 follow-up). Visual agreement of MR perfusion with rapid wash-out by rating were found in 44 ± 40% for initial diagnosis, and 75 ± 31% for follow-up. We found a strong correlation (Pearson coefficient 0.92, p < 0.001) between the measured volumes of MR perfusion and rapid wash-out. The measured volumes of MR perfusion and rapid wash-out did not differ significantly. Small lesions were often not detected by MR perfusion. Nevertheless, the measured volumes showed no significant differences in this small cohort. Rapid wash-out calculation is a simple tool that provides new information and, when used in conjunction with MR perfusion, may increase diagnostic accuracy. The method shows promising results, particularly in the evaluation of small lesions.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12885-024-12883-6
Martha A. Cancilla, Donya Nemati, Danielle Halsey, Niraj Shah, Melissa Sherman, Nicholas Kelly, Pengyue Zhang, Nada Kassem, Navin Kaushal, Kelly Shanahan, Lesley Kailani Glenn, Jennifer A. Ligibel, Tarah J. Ballinger
Exercise is associated with improved survival, physical functioning, treatment tolerability, and quality of life in early-stage breast cancer. These same endpoints matter in metastatic breast cancer (MBC). Prior trials in MBC have found exercise to be not feasible or of limited benefit, possibly due to inclusion of patients with heterogeneous disease trajectories. Patients with MBC have variable disease trajectories and supportive care needs; those with indolent MBC have longer life expectancy, lower symptom burden and distinct priorities, and are well-positioned to participate in and benefit from an exercise program. The EMBody trial aims to determine the impact of a multimodal exercise intervention on cardiorespiratory fitness, physical function, body composition, and patient-reported outcomes, specifically in patients with stable, indolent MBC. Eligible patients have MBC with no evidence of disease progression on current therapy in the prior 12 months and cannot be receiving cytotoxic chemotherapy. The trial aims to enroll 100 patients, randomized 1:1 to the exercise intervention versus usual care, stratified by baseline function. The virtually-delivered exercise intervention arm achieves moderate intensity exercise with exercise physiologists 3 days/week for 16 weeks. The 60-minute sessions include aerobic, resistance, balance and stretching exercises. The exercise arm receives informational sessions on the role of exercise in cancer and principles of habit and self-efficacy. The primary endpoint is 16 week change in fitness on a ramp treadmill test between the exercise and control arms. Secondary endpoints include change in a physical function, muscle mass assessed by CT scans, and PROs of fatigue and quality of life. Exploratory analysis includes behavioral modifiers of exercise adherence and effectiveness and serologic measures of inflammatory, metabolic, and immune pathway biomarkers. The EMBody trial evaluates exercise in a unique patient population with indolent, non-progressive MBC. Patients living with MBC experience similar symptom burden to those undergoing therapy for early-stage disease and the benefits achieved with exercise could be similarly impactful. This trial will contribute evidence to support expansion of exercise recommendations, among other survivorship care efforts, to those living with metastatic disease. Clinical trial information: NCT05468034. NCT05468034. Date of registration: 7/12/2022.
在早期乳腺癌患者中，运动与生存期、身体机能、治疗耐受性和生活质量的改善有关。这些终点对转移性乳腺癌（MBC）同样重要。之前对 MBC 进行的试验发现，运动并不可行或获益有限，这可能是由于纳入了不同疾病轨迹的患者。MBC患者的疾病轨迹和支持性护理需求各不相同；而惰性MBC患者的预期寿命较长、症状负担较轻且有不同的优先考虑事项，他们完全有能力参与锻炼计划并从中获益。EMBody 试验旨在确定多模式运动干预对心肺功能、身体机能、身体成分和患者报告结果的影响，特别是对病情稳定、不活跃的 MBC 患者的影响。符合条件的 MBC 患者在过去 12 个月内接受当前治疗后无疾病进展迹象，且不能接受细胞毒性化疗。该试验的目标是招募 100 名患者，按基线功能分层，以 1:1 随机分配给运动干预与常规护理。虚拟运动干预组在运动生理学家的指导下进行中等强度的运动，每周 3 天，共 16 周。60 分钟的课程包括有氧、阻力、平衡和伸展运动。运动干预组将接受关于运动在癌症中的作用以及习惯和自我效能原则的信息讲座。主要终点是运动组和对照组在斜坡跑步机测试中 16 周的体能变化。次要终点包括身体机能的变化、CT 扫描评估的肌肉质量以及疲劳和生活质量的主要指标。探索性分析包括运动依从性和有效性的行为调节因素，以及炎症、代谢和免疫途径生物标记物的血清学测量。EMBody 试验评估的是一个独特的患者群体，他们都是非进展性、轻度 MBC 患者。MBC 患者的症状负担与接受早期疾病治疗的患者相似，而通过锻炼获得的益处可能会产生类似的影响。这项试验将为支持将运动建议和其他幸存者护理工作扩展到转移性疾病患者提供证据。临床试验信息：NCT05468034。NCT05468034。注册日期：7/12/2022.
{"title":"Exercise as part of survivorship care in metastatic breast cancer: protocol for the randomized EMBody trial","authors":"Martha A. Cancilla, Donya Nemati, Danielle Halsey, Niraj Shah, Melissa Sherman, Nicholas Kelly, Pengyue Zhang, Nada Kassem, Navin Kaushal, Kelly Shanahan, Lesley Kailani Glenn, Jennifer A. Ligibel, Tarah J. Ballinger","doi":"10.1186/s12885-024-12883-6","DOIUrl":"https://doi.org/10.1186/s12885-024-12883-6","url":null,"abstract":"Exercise is associated with improved survival, physical functioning, treatment tolerability, and quality of life in early-stage breast cancer. These same endpoints matter in metastatic breast cancer (MBC). Prior trials in MBC have found exercise to be not feasible or of limited benefit, possibly due to inclusion of patients with heterogeneous disease trajectories. Patients with MBC have variable disease trajectories and supportive care needs; those with indolent MBC have longer life expectancy, lower symptom burden and distinct priorities, and are well-positioned to participate in and benefit from an exercise program. The EMBody trial aims to determine the impact of a multimodal exercise intervention on cardiorespiratory fitness, physical function, body composition, and patient-reported outcomes, specifically in patients with stable, indolent MBC. Eligible patients have MBC with no evidence of disease progression on current therapy in the prior 12 months and cannot be receiving cytotoxic chemotherapy. The trial aims to enroll 100 patients, randomized 1:1 to the exercise intervention versus usual care, stratified by baseline function. The virtually-delivered exercise intervention arm achieves moderate intensity exercise with exercise physiologists 3 days/week for 16 weeks. The 60-minute sessions include aerobic, resistance, balance and stretching exercises. The exercise arm receives informational sessions on the role of exercise in cancer and principles of habit and self-efficacy. The primary endpoint is 16 week change in fitness on a ramp treadmill test between the exercise and control arms. Secondary endpoints include change in a physical function, muscle mass assessed by CT scans, and PROs of fatigue and quality of life. Exploratory analysis includes behavioral modifiers of exercise adherence and effectiveness and serologic measures of inflammatory, metabolic, and immune pathway biomarkers. The EMBody trial evaluates exercise in a unique patient population with indolent, non-progressive MBC. Patients living with MBC experience similar symptom burden to those undergoing therapy for early-stage disease and the benefits achieved with exercise could be similarly impactful. This trial will contribute evidence to support expansion of exercise recommendations, among other survivorship care efforts, to those living with metastatic disease. Clinical trial information: NCT05468034. NCT05468034. Date of registration: 7/12/2022.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12885-024-12884-5
Xiaoshan Liu, Xiaomin Peng, Shu Yang, Haijin Liu, Shouhua Zhang, Jinhu Wang, Yuhan Ma, Yu Wu, Zhixuan Wang, Wenjun Weng, Yang Li
In patients with relapsed or refractory neuroblastoma (NB), the limited efficacy of conventional chemotherapies necessitates the exploration of new treatment options. Previous studies have highlighted the anti-tumor properties of arsenic trioxide (ATO) in high-risk NB (HR-NB). This study aims to assess the effectiveness and safety of ATO combined with salvage chemotherapy regimens, featuring cyclophosphamide and topotecan, as a foundational treatment for children with relapsed or refractory NB. Eleven patients (four relapsed, seven refractory NB) were retrospectively analyzed for efficacy and treatment relevance. Salvage treatments, incorporating ATO (0.18 mg/kg daily for 8 h intravenously on days 1 to 10), were administered upon disease progression or relapse, with assessments conducted every two cycles. Treatments had 63.6% efficacy, with six cases of partial response, one case of stable disease, and four cases of disease progression. The overall response rate was 54.5%, and the disease control rate was 63.6%. Importantly, the systemic toxicity experienced by patients following salvage chemotherapy with ATO was mild. Salvage chemotherapy regimens featuring ATO demonstrated potential for prolonging disease stabilization for relapsed or refractory HR-NB patients, exhibiting both favorable efficacy and safety profiles. This suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB. Point 1. The inadequate effectiveness of traditional chemotherapy in individuals with recurrent or resistant neuroblastoma (NB) necessitates the investigation of novel therapeutic approaches. Point 2. Arsenic trioxide (ATO)-based salvage treatments are both effective and less toxic in relapsed or refractory NB. Point 3. Salvage chemotherapy regimens incorporating ATO have shown promise in extending disease stabilization in relapsed or refractory high-risk NB patients, with favorable efficacy and safety profiles, which suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.
对于复发或难治性神经母细胞瘤（NB）患者，传统化疗的疗效有限，因此有必要探索新的治疗方案。先前的研究强调了三氧化二砷（ATO）在高危神经母细胞瘤（HR-NB）中的抗肿瘤特性。本研究旨在评估三氧化二砷联合环磷酰胺和托泊替康等挽救性化疗方案作为复发或难治性NB儿童基础治疗的有效性和安全性。我们对11例患者（4例复发，7例难治性NB）的疗效和治疗相关性进行了回顾性分析。在疾病进展或复发时进行挽救治疗，包括ATO（每天0.18毫克/千克，第1至10天静脉注射8小时），每两个周期进行一次评估。疗效为63.6%，其中6例部分应答，1例病情稳定，4例病情进展。总体反应率为 54.5%，疾病控制率为 63.6%。重要的是，使用 ATO 进行挽救性化疗后，患者全身毒性较轻。以ATO为特色的挽救性化疗方案显示出延长复发或难治HR-NB患者病情稳定期的潜力，并表现出良好的疗效和安全性。这表明，在治疗 NB 时应进一步临床探索和推广这种治疗方法。要点 1.传统化疗对复发性或耐药性神经母细胞瘤（NB）患者的疗效不佳，因此有必要研究新型治疗方法。要点 2.以三氧化二砷（ATO）为基础的挽救治疗对复发或难治性 NB 既有效又毒性较低。要点 3.在复发或难治的高危 NB 患者中，含有 ATO 的挽救性化疗方案有望延长疾病稳定期，且疗效和安全性良好，这表明在 NB 治疗中应进一步进行临床探索和推广。
{"title":"Salvage chemotherapy regimens with arsenic trioxide for relapsed or refractory neuroblastoma: a promising approach","authors":"Xiaoshan Liu, Xiaomin Peng, Shu Yang, Haijin Liu, Shouhua Zhang, Jinhu Wang, Yuhan Ma, Yu Wu, Zhixuan Wang, Wenjun Weng, Yang Li","doi":"10.1186/s12885-024-12884-5","DOIUrl":"https://doi.org/10.1186/s12885-024-12884-5","url":null,"abstract":"In patients with relapsed or refractory neuroblastoma (NB), the limited efficacy of conventional chemotherapies necessitates the exploration of new treatment options. Previous studies have highlighted the anti-tumor properties of arsenic trioxide (ATO) in high-risk NB (HR-NB). This study aims to assess the effectiveness and safety of ATO combined with salvage chemotherapy regimens, featuring cyclophosphamide and topotecan, as a foundational treatment for children with relapsed or refractory NB. Eleven patients (four relapsed, seven refractory NB) were retrospectively analyzed for efficacy and treatment relevance. Salvage treatments, incorporating ATO (0.18 mg/kg daily for 8 h intravenously on days 1 to 10), were administered upon disease progression or relapse, with assessments conducted every two cycles. Treatments had 63.6% efficacy, with six cases of partial response, one case of stable disease, and four cases of disease progression. The overall response rate was 54.5%, and the disease control rate was 63.6%. Importantly, the systemic toxicity experienced by patients following salvage chemotherapy with ATO was mild. Salvage chemotherapy regimens featuring ATO demonstrated potential for prolonging disease stabilization for relapsed or refractory HR-NB patients, exhibiting both favorable efficacy and safety profiles. This suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB. Point 1. The inadequate effectiveness of traditional chemotherapy in individuals with recurrent or resistant neuroblastoma (NB) necessitates the investigation of novel therapeutic approaches. Point 2. Arsenic trioxide (ATO)-based salvage treatments are both effective and less toxic in relapsed or refractory NB. Point 3. Salvage chemotherapy regimens incorporating ATO have shown promise in extending disease stabilization in relapsed or refractory high-risk NB patients, with favorable efficacy and safety profiles, which suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Curcumin has been reported to have activity for prevention and therapy of CRC, yet its underlying mechanisms remain largely unknown. Recently, emerging evidence suggests that the gut microbiota and its metabolites contribute to the causation and progression of Colorectal cancer (CRC). In this study, we aimed to investigate if curcumin affects the tumorigenesis of CRC by modulating gut microbiota and its metabolites. Forty male C57BL/6JGpt mice were randomly divided into four groups: negative control (NC), curcumin control, CRC model, and curcumin treatment (CRC-Cur) groups. CRC mouse model was induced by using azoxymethane (AOM) and dextran sodium sulfate (DSS), and the mice in CRC model and curcumin treatment groups received oral PBS or curcumin (150 mg/kg/day), respectively. Additionally, fecal samples were collected. 16 S rRNA sequencing and Liquid Chromatography Mass Spectrometry (LC-MS)-based untargeted metabolomics were used to observe the changes of intestinal flora and intestinal metabolites. Curcumin treatment restored colon length and structural morphology, and significantly inhibited tumor formation in AOM/DSS-induced CRC model mice. The 16S rRNA sequencing analysis indicated that the diversity and richness of core and total species of intestinal microflora in the CRC group were significantly lower than those in the NC group, which were substantially restored in the curcumin treatment group. Curcumin reduced harmful bacteria, including Ileibacterium, Monoglobus and Desulfovibrio, which were elevated in CRC model mice. Moreover, curcumin increased the abundance of Clostridia_UCG-014, Bifidobacterium and Lactobacillus, which were decreased in CRC model mice. In addition, 13 different metabolites were identified. Compared to the NC group, ethosuximide, xanthosine, and 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) were elevated in the CRC model group, whereas curcumin treatment significantly reduced their levels. Conversely, glutamylleucine, gamma-Glutamylleucine, liquiritin, ubenimex, 5’-deoxy-5’-fluorouridine, 7,8-Dihydropteroic acid, neobyakangelicol, libenzapril, xenognosin A, and 7,4’-dihydroxy-8-methylflavan were decreased in the CRC group but notably upregulated by curcumin. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed enrichment in seven pathways, including folate biosynthesis (P < 0.05). The gut microecological balance was disrupted in AOM/DSS-induced CRC mice, accompanied by metabolite dysbiosis. Curcumin restored the equilibrium of the microbiota and regulated metabolites, highly indicating that curcumin may alleviate the development of AOM/DSS induced colorectal cancer in mice by regulating intestinal flora homeostasis and intestinal metabolites.
{"title":"Curcumin suppresses colorectal tumorigenesis through restoring the gut microbiota and metabolites","authors":"Wenxin Deng, Xiaojian Xiong, Mingyang Lu, Shibo Huang, Yunfei Luo, Yujie Wang, Ying Ying","doi":"10.1186/s12885-024-12898-z","DOIUrl":"https://doi.org/10.1186/s12885-024-12898-z","url":null,"abstract":"Curcumin has been reported to have activity for prevention and therapy of CRC, yet its underlying mechanisms remain largely unknown. Recently, emerging evidence suggests that the gut microbiota and its metabolites contribute to the causation and progression of Colorectal cancer (CRC). In this study, we aimed to investigate if curcumin affects the tumorigenesis of CRC by modulating gut microbiota and its metabolites. Forty male C57BL/6JGpt mice were randomly divided into four groups: negative control (NC), curcumin control, CRC model, and curcumin treatment (CRC-Cur) groups. CRC mouse model was induced by using azoxymethane (AOM) and dextran sodium sulfate (DSS), and the mice in CRC model and curcumin treatment groups received oral PBS or curcumin (150 mg/kg/day), respectively. Additionally, fecal samples were collected. 16 S rRNA sequencing and Liquid Chromatography Mass Spectrometry (LC-MS)-based untargeted metabolomics were used to observe the changes of intestinal flora and intestinal metabolites. Curcumin treatment restored colon length and structural morphology, and significantly inhibited tumor formation in AOM/DSS-induced CRC model mice. The 16S rRNA sequencing analysis indicated that the diversity and richness of core and total species of intestinal microflora in the CRC group were significantly lower than those in the NC group, which were substantially restored in the curcumin treatment group. Curcumin reduced harmful bacteria, including Ileibacterium, Monoglobus and Desulfovibrio, which were elevated in CRC model mice. Moreover, curcumin increased the abundance of Clostridia_UCG-014, Bifidobacterium and Lactobacillus, which were decreased in CRC model mice. In addition, 13 different metabolites were identified. Compared to the NC group, ethosuximide, xanthosine, and 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) were elevated in the CRC model group, whereas curcumin treatment significantly reduced their levels. Conversely, glutamylleucine, gamma-Glutamylleucine, liquiritin, ubenimex, 5’-deoxy-5’-fluorouridine, 7,8-Dihydropteroic acid, neobyakangelicol, libenzapril, xenognosin A, and 7,4’-dihydroxy-8-methylflavan were decreased in the CRC group but notably upregulated by curcumin. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed enrichment in seven pathways, including folate biosynthesis (P < 0.05). The gut microecological balance was disrupted in AOM/DSS-induced CRC mice, accompanied by metabolite dysbiosis. Curcumin restored the equilibrium of the microbiota and regulated metabolites, highly indicating that curcumin may alleviate the development of AOM/DSS induced colorectal cancer in mice by regulating intestinal flora homeostasis and intestinal metabolites.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1186/s12885-024-12897-0
Yue-Chen Zhao, Yun-Feng Li, Ling Qiu, Shun-Zi Jin, Yan-Nan Shen, Chao-He Zhang, Jie Cui, Tie-Jun Wang
Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.
{"title":"SQLE—a promising prognostic biomarker in cervical cancer: implications for tumor malignant behavior, cholesterol synthesis, epithelial-mesenchymal transition, and immune infiltration","authors":"Yue-Chen Zhao, Yun-Feng Li, Ling Qiu, Shun-Zi Jin, Yan-Nan Shen, Chao-He Zhang, Jie Cui, Tie-Jun Wang","doi":"10.1186/s12885-024-12897-0","DOIUrl":"https://doi.org/10.1186/s12885-024-12897-0","url":null,"abstract":"Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Crohn’s disease (CD), a prominent manifestation of chronic gastrointestinal inflammation, and breast cancer (BC), seemingly disparate in the medical domain, exhibit a shared characteristic. This convergence arises from their involvement in chronic inflammation and immune responses, an aspect that has progressively captivated the attention of investigators but remain controversial. We used two-sample Mendelian Randomization (MR) and transcriptomics to explore the relationship between CD and BC. MR assessed causality of CD on different BC subtypes and reverse causality of BC on CD. We identified CD-related differentially expressed genes and their prognostic impact on BC, and developed a new molecular BC classification based on these key genes. MR revealed a causal link between CD and increased BC risk, especially in estrogen receptor-positive (ER+) patients, but not in ER-negative (ER-) cases. BC showed no causal effect on CD. Transcriptomics pinpointed genes like B4GALNT2 and FGF19 that affected BC prognosis in CD patients. A nomogram based on these genes predicted BC outcomes with high accuracy. Using these genes, a new molecular classification of BC patients was proposed. CD is a risk factor for ER + BC but not for ER- BC. BC does not causally affect CD. Our prognostic model and new BC molecular classifications offer insights for personalized treatment strategies.
克罗恩病（Crohn's disease，CD）是慢性胃肠道炎症的一种突出表现，而乳腺癌（BC）在医学领域看似毫不相干，但却具有共同的特征。这种共同之处在于它们都参与了慢性炎症和免疫反应，这一点逐渐引起了研究人员的关注，但仍存在争议。我们使用双样本孟德尔随机化（MR）和转录组学来探讨 CD 和 BC 之间的关系。MR评估了CD对不同BC亚型的因果关系，以及BC对CD的反向因果关系。我们确定了与 CD 相关的差异表达基因及其对 BC 预后的影响，并根据这些关键基因建立了新的 BC 分子分类。磁共振成像显示，CD与BC风险增加之间存在因果关系，尤其是在雌激素受体阳性（ER+）患者中，而在ER阴性（ER-）病例中则没有这种关系。BC与CD没有因果关系。转录组学发现，B4GALNT2 和 FGF19 等基因会影响 CD 患者的 BC 预后。基于这些基因的提名图能高精度地预测 BC 的预后。利用这些基因，提出了一种新的 BC 患者分子分类方法。CD是ER+BC的风险因素，但不是ER-BC的风险因素。BC与CD没有因果关系。我们的预后模型和新的BC分子分类为个性化治疗策略提供了启示。
{"title":"Unraveling the causal links and novel molecular classification of Crohn’s disease in breast Cancer: a two-sample mendelian randomization and transcriptome analysis with prognostic modeling","authors":"Xin Yu, Yushuai Yu, Xiewei Huang, Zirong Jiang, Qing Wang, Xiaoqin Yu, Chuangui Song","doi":"10.1186/s12885-024-12838-x","DOIUrl":"https://doi.org/10.1186/s12885-024-12838-x","url":null,"abstract":"Crohn’s disease (CD), a prominent manifestation of chronic gastrointestinal inflammation, and breast cancer (BC), seemingly disparate in the medical domain, exhibit a shared characteristic. This convergence arises from their involvement in chronic inflammation and immune responses, an aspect that has progressively captivated the attention of investigators but remain controversial. We used two-sample Mendelian Randomization (MR) and transcriptomics to explore the relationship between CD and BC. MR assessed causality of CD on different BC subtypes and reverse causality of BC on CD. We identified CD-related differentially expressed genes and their prognostic impact on BC, and developed a new molecular BC classification based on these key genes. MR revealed a causal link between CD and increased BC risk, especially in estrogen receptor-positive (ER+) patients, but not in ER-negative (ER-) cases. BC showed no causal effect on CD. Transcriptomics pinpointed genes like B4GALNT2 and FGF19 that affected BC prognosis in CD patients. A nomogram based on these genes predicted BC outcomes with high accuracy. Using these genes, a new molecular classification of BC patients was proposed. CD is a risk factor for ER + BC but not for ER- BC. BC does not causally affect CD. Our prognostic model and new BC molecular classifications offer insights for personalized treatment strategies.","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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