Jinhai Tian, Xu Cao, Zongying Jiang, Jia Wang, Wan Fan, Shaoting Zhang, Sien Zhao, Jianmin Sun
Background
Colorectal cancer (CRC) is a prevalent and lethal tumor, with metastasis being the leading cause of mortality. Previous research has indicated that the long non-coding RNA (lncRNA) CCAT2 is involved in the regulation of various tumor progression mechanisms. However, the precise role of CCAT2 in CRC proliferation and metastasis remains ambiguous. This study seeks to elucidate the mechanisms through which CCAT2 influences CRC.
Methods
High-throughput sequencing and RT-qPCR were used to detect CCAT2 expression in CRC. Functional analyses including CCK8, colony formation, wound healing migration, transwell chamber, and Muse® Cell Analyzer assays were performed to study the effects of CCAT2 gene deletion on CRC cells. RNA-pulldown and protein mass spectrometry were employed to identify the interaction between CCAT2 and GNB2 protein.
Results
Increased CCAT2 expression was found in CRC, especially in metastatic CRC. Deletion of CCAT2 gene inhibited CRC cell proliferation, migration, and invasion while promoting apoptosis. The interaction between CCAT2 and GNB2 protein was shown to modulate GNB2 protein alterations and affect the ERK and Wnt signaling pathways, thereby promoting CRC proliferation and metastasis.
Conclusion
CCAT2 plays a crucial role in CRC progression by modulating the ERK and Wnt signaling pathways through its interaction with GNB2. These findings highlight the importance of CCAT2 as a key regulatory element in the mechanisms underlying CRC proliferation and metastasis.
{"title":"LncRNA CCAT2 promotes the proliferation and metastasis of colorectal cancer through activation of the ERK and Wnt signaling pathways by regulating GNB2 expression","authors":"Jinhai Tian, Xu Cao, Zongying Jiang, Jia Wang, Wan Fan, Shaoting Zhang, Sien Zhao, Jianmin Sun","doi":"10.1002/cam4.70169","DOIUrl":"10.1002/cam4.70169","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal cancer (CRC) is a prevalent and lethal tumor, with metastasis being the leading cause of mortality. Previous research has indicated that the long non-coding RNA (lncRNA) CCAT2 is involved in the regulation of various tumor progression mechanisms. However, the precise role of CCAT2 in CRC proliferation and metastasis remains ambiguous. This study seeks to elucidate the mechanisms through which CCAT2 influences CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>High-throughput sequencing and RT-qPCR were used to detect CCAT2 expression in CRC. Functional analyses including CCK8, colony formation, wound healing migration, transwell chamber, and Muse® Cell Analyzer assays were performed to study the effects of CCAT2 gene deletion on CRC cells. RNA-pulldown and protein mass spectrometry were employed to identify the interaction between CCAT2 and GNB2 protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Increased CCAT2 expression was found in CRC, especially in metastatic CRC. Deletion of CCAT2 gene inhibited CRC cell proliferation, migration, and invasion while promoting apoptosis. The interaction between CCAT2 and GNB2 protein was shown to modulate GNB2 protein alterations and affect the ERK and Wnt signaling pathways, thereby promoting CRC proliferation and metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CCAT2 plays a crucial role in CRC progression by modulating the ERK and Wnt signaling pathways through its interaction with GNB2. These findings highlight the importance of CCAT2 as a key regulatory element in the mechanisms underlying CRC proliferation and metastasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118520","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}
Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence-based approaches are urgently needed to optimize treatment.
Methods
A systematic review and network meta-analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model.
Results
Seven placebo-controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83–8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73–6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84–2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42–2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07–0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30–2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42–1.88). However, network meta-analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety.
Conclusion
Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.
背景：癌症恶病质影响着一半以上的癌症患者，降低了他们的生存率。目前迫切需要基于证据的方法来优化治疗：方法：我们进行了一项系统综述和网络荟萃分析，以评估不同药物疗法治疗癌症恶病质的有效性和安全性。检索了 2000 年 1 月 1 日至 2024 年 3 月 20 日期间的三个数据库（PubMed、Cochrane Library 和 Web of Science）。采用随机效应模型，使用 R 软件中的 netmeta 软件包计算汇总效应：结果：分析了涉及 1421 名患者的七项安慰剂对照随机试验。配对分析显示，奥氮平的体重增加幅度为4.6千克（95%置信区间[CI] 0.83-8.37千克），埃辛洛尔（20毫克）的体重增加幅度为3.82千克（95%置信区间0.73-6.91千克），阿那莫瑞林（100毫克）的体重增加幅度为2.36千克（95%置信区间1.84-2.89千克），阿那莫瑞林（50毫克）的体重增加幅度为1.31千克（95%置信区间0.42-2.19千克）。在安全性方面，与安慰剂相比，奥氮平的几率最低，为 0.26（95% CI 0.07-0.94），其次是阿那莫瑞林（50 毫克），为 0.86（95% CI 0.30-2.48），阿那莫瑞林（100 毫克）为 0.89（95% CI 0.42-1.88）。然而，网络荟萃分析无法证实奥氮平在疗效和安全性方面优于阿那莫瑞林：结论：奥氮平和阿那莫林都有助于改善癌症恶病质患者的体重。个性化治疗可能对不同患者有所帮助。
{"title":"Efficacy and safety of pharmacotherapy for cancer cachexia: A systematic review and network meta-analysis","authors":"Hao Chen, Masashi Ishihara, Hiroki Kazahari, Ryusuke Ochiai, Shigeru Tanzawa, Takeshi Honda, Yasuko Ichikawa, Nobuyuki Horita, Hisashi Nagai, Kiyotaka Watanabe, Nobuhiko Seki","doi":"10.1002/cam4.70166","DOIUrl":"10.1002/cam4.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence-based approaches are urgently needed to optimize treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review and network meta-analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven placebo-controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83–8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73–6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84–2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42–2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07–0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30–2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42–1.88). However, network meta-analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118519","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}
Camille Tessier, Richard LeBlanc, Jean Roy, Sabrina Trudel, Julie Côté, Marc Lalancette, Jean-Samuel Boudreault, Émilie Lemieux-Blanchard, Rayan Kaedbey, Michel Pavic
Background
Plasma cell leukemia (PCL) is a rare monoclonal gammopathy, associated with short survival. Because of its very low incidence, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand the clinical features, prognostic factors, and efficacy of modern treatments in both primary PCL (pPCL) and secondary PCL (sPCL).
Methods
We performed a retrospective, multicenter study of patients diagnosed with PCL, defined as circulating plasma cells ≥20% of total leukocytes and/or ≥2 × 109/L.
Results
We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. The median progression-free survival (PFS) to frontline treatment and overall survival (OS) were, respectively, 4.8 (95% CI, 0.4–9.2) and 18.3 months (95% CI, 0.0–39.0) for pPCL and 0.8 (95% CI, 0.5–1.1) and 1.2 months (95% CI, 0.9–1.5) for sPCL (both p < 0.001). We observed no improvement in OS over time (2005–2012 vs. 2013–2020, p = 0.629 for pPCL and p = 0.329 for sPCL). Finally, our data suggested that sPCL originates from a high-risk multiple myeloma (MM) population with a short OS (median 30.2 months), early relapse after stem cell transplant (median 11.9 months) and a high proportion of patients with multiple cytogenetic abnormalities (36% with ≥2 abnormalities).
Conclusions
This study is one of the largest PCL cohorts reported. We are also the first to investigate characteristics of MM before its transformation into sPCL and demonstrate that high-risk biologic features already present at the time of MM diagnosis. Moreover, our data highlights the lack of improvement in PCL survival in recent years and the urgent need for better treatment options.
{"title":"Poor outcome despite modern treatments: A retrospective study of 99 patients with primary and secondary plasma cell leukemia","authors":"Camille Tessier, Richard LeBlanc, Jean Roy, Sabrina Trudel, Julie Côté, Marc Lalancette, Jean-Samuel Boudreault, Émilie Lemieux-Blanchard, Rayan Kaedbey, Michel Pavic","doi":"10.1002/cam4.70192","DOIUrl":"10.1002/cam4.70192","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Plasma cell leukemia (PCL) is a rare monoclonal gammopathy, associated with short survival. Because of its very low incidence, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand the clinical features, prognostic factors, and efficacy of modern treatments in both primary PCL (pPCL) and secondary PCL (sPCL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a retrospective, multicenter study of patients diagnosed with PCL, defined as circulating plasma cells ≥20% of total leukocytes and/or ≥2 × 10<sup>9</sup>/L.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. The median progression-free survival (PFS) to frontline treatment and overall survival (OS) were, respectively, 4.8 (95% CI, 0.4–9.2) and 18.3 months (95% CI, 0.0–39.0) for pPCL and 0.8 (95% CI, 0.5–1.1) and 1.2 months (95% CI, 0.9–1.5) for sPCL (both <i>p</i> < 0.001). We observed no improvement in OS over time (2005–2012 vs. 2013–2020, <i>p</i> = 0.629 for pPCL and <i>p</i> = 0.329 for sPCL). Finally, our data suggested that sPCL originates from a high-risk multiple myeloma (MM) population with a short OS (median 30.2 months), early relapse after stem cell transplant (median 11.9 months) and a high proportion of patients with multiple cytogenetic abnormalities (36% with ≥2 abnormalities).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study is one of the largest PCL cohorts reported. We are also the first to investigate characteristics of MM before its transformation into sPCL and demonstrate that high-risk biologic features already present at the time of MM diagnosis. Moreover, our data highlights the lack of improvement in PCL survival in recent years and the urgent need for better treatment options.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118528","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}
Jieran Long, Xuefei Li, Lin Wu, Guohua Yu, Aimin Zang, Yanqiu Zhao, Jinsheng Shi, Ligong Nie, Xuan Zhao, Jian Fang
Purpose
To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second-line monotherapy for treating small-cell lung cancer (SCLC) patients.
Methods
According to the “3 + 3” dose-escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m2 once every 3 weeks for four cycles. Progression-free survival (PFS), overall survival (OS), median progression-free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan–Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS.
Results
This study included 29 patients with stage III–IV SCLC (stage IIIa, n = 1; stage IIIb, n = 1; and stage IV, n = 27). Of these, 26 patients were enrolled in the 180 mg/m2 dose group, and 3 patients were enrolled in the 220 mg/m2 dose group. No dose-limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m2 group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m2 group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m2 group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m2 group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively.
Conclusion
JK1201I exhibits promising efficacy and relatively low toxicities as a second-line monotherapy for SCLC, warranting further large-scale clinical studies to evaluate its efficacy in greater detail.
{"title":"Phase Ib/II study on the safety, tolerability, and preliminary efficacy of pegylated irinotecan (JK1201I) as second-line monotherapy for patients with small-cell lung cancer","authors":"Jieran Long, Xuefei Li, Lin Wu, Guohua Yu, Aimin Zang, Yanqiu Zhao, Jinsheng Shi, Ligong Nie, Xuan Zhao, Jian Fang","doi":"10.1002/cam4.70059","DOIUrl":"10.1002/cam4.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second-line monotherapy for treating small-cell lung cancer (SCLC) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>According to the “3 + 3” dose-escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m<sup>2</sup> once every 3 weeks for four cycles. Progression-free survival (PFS), overall survival (OS), median progression-free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan–Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study included 29 patients with stage III–IV SCLC (stage IIIa, <i>n</i> = 1; stage IIIb, <i>n</i> = 1; and stage IV, <i>n</i> = 27). Of these, 26 patients were enrolled in the 180 mg/m<sup>2</sup> dose group, and 3 patients were enrolled in the 220 mg/m<sup>2</sup> dose group. No dose-limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m<sup>2</sup> group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m<sup>2</sup> group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m<sup>2</sup> group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m<sup>2</sup> group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>JK1201I exhibits promising efficacy and relatively low toxicities as a second-line monotherapy for SCLC, warranting further large-scale clinical studies to evaluate its efficacy in greater detail.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118527","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}
Lymphoma is the most common secondary cause of hemophagocytic lymphohistiocytosis (HLH) in adults. Lymphoma-associated HLH (LA-HLH) in the elderly population is not rare, however, little has been reported regarding clinicopathological characteristics, prognostic factors, and outcomes of LA-HLH in the elderly population.
Methods
We retrospectively analyzed a multicenter cohort of elderly patients with LA-HLH. Clinicopathological features and treatment information were collected. The impacts of baseline characteristics and treatments on survival outcomes were analyzed.
Results
A total of 173 elderly patients with LA-HLH were included. Compared with young patients, elderly patients showed different clinical and laboratory features. Regarding lymphoma subtypes, B-cell lymphoma was more common in elderly patients (elderly 61.3% vs. young 32.3%, p < 0.001) while T/NK-cell lymphoma was more common in young patients (65.3% vs. 35.3%, p < 0.001). The median survival of elderly patients with LA-HLH was only 92 days. The prior use of HLH therapy or etoposide-containing HLH therapy was not associated with improved overall survival. T/NK-cell subtype, a lower platelet count (≤53 × 109/L), a lower albumin level (≤32.1 g/L), a higher LDH level (>1407 U/L), and a higher creatinine level (>96.8 μmol/L) were independent predictors of decreased overall survival and 60-day survival. A prognostic index was established and demonstrated to be robust in predicting the overall survival and 60-day survival of elderly patients with LA-HLH.
Conclusions
LA-HLH in elderly patients displayed heterogeneous clinicopathological features and survival outcomes. Treatments need to be optimized to improve the outcomes of elderly patients with LA-HLH.
{"title":"Clinicopathological characteristics, prognostic factors, and outcomes of elderly patients with lymphoma-associated hemophagocytic lymphohistiocytosis: A multicenter analysis","authors":"Yi Miao, Jing Zhang, Xuzhang Lu, Meng Wu, Bingzong Li, Liang Yu, Miao Sun, Yun Zhuang, Yuqing Miao, Haiwen Ni, Xiaoyan Xie, Jingyan Xu, Yunping Zhang, Min Zhao, Min Xu, Wanchuan Zhuang, Weiying Gu, Guoqiang Lin, Haiying Hua, Jianfeng Zhu, Maozhong Xu, Tao Jia, Ping Liu, Lijia Zhai, Tongtong Zhang, Qiurong Shan, Qiudan Shen, Jun Qian, Chunling Wang, Jianyong Li, Wenyu Shi","doi":"10.1002/cam4.70178","DOIUrl":"10.1002/cam4.70178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lymphoma is the most common secondary cause of hemophagocytic lymphohistiocytosis (HLH) in adults. Lymphoma-associated HLH (LA-HLH) in the elderly population is not rare, however, little has been reported regarding clinicopathological characteristics, prognostic factors, and outcomes of LA-HLH in the elderly population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed a multicenter cohort of elderly patients with LA-HLH. Clinicopathological features and treatment information were collected. The impacts of baseline characteristics and treatments on survival outcomes were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 173 elderly patients with LA-HLH were included. Compared with young patients, elderly patients showed different clinical and laboratory features. Regarding lymphoma subtypes, B-cell lymphoma was more common in elderly patients (elderly 61.3% vs. young 32.3%, <i>p</i> < 0.001) while T/NK-cell lymphoma was more common in young patients (65.3% vs. 35.3%, <i>p</i> < 0.001). The median survival of elderly patients with LA-HLH was only 92 days. The prior use of HLH therapy or etoposide-containing HLH therapy was not associated with improved overall survival. T/NK-cell subtype, a lower platelet count (≤53 × 10<sup>9</sup>/L), a lower albumin level (≤32.1 g/L), a higher LDH level (>1407 U/L), and a higher creatinine level (>96.8 μmol/L) were independent predictors of decreased overall survival and 60-day survival. A prognostic index was established and demonstrated to be robust in predicting the overall survival and 60-day survival of elderly patients with LA-HLH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LA-HLH in elderly patients displayed heterogeneous clinicopathological features and survival outcomes. Treatments need to be optimized to improve the outcomes of elderly patients with LA-HLH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102532","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}
Ting Sun, Yiwen Qiu, Tao Wang, Yi Yang, Haizhou Qiu, Shu Shen, Huasheng Pang, Wentao Wang
Background
Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status.
Methods
This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics.
Results
Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348–3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537–4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001).
Conclusions
These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.
背景：尽管核苷类似物（NAs）被认为可降低乙型肝炎病毒（HBV）相关肝细胞癌（HCC）的风险，但肝切除术后停用NAs对HBV相关HCC预后的影响却鲜有报道。我们旨在研究乙肝病毒e抗原（HBeAg）阴性的HBV相关HCC患者根据术前乙肝病毒表面抗原（HBsAg）状态停用NAs的可能性：这项历史队列研究涉及2014年至2019年期间因HBV相关HCC接受根治性肝切除术的1232例NA治疗的HBeAg阴性患者。研究人员比较了手术前停止NA治疗的患者与继续NA治疗的患者的无复发生存期（RFS）和总生存期（OS）。采用倾向评分匹配法（PSM）平衡基线特征：在所有入组患者中，有839名（68.1%）患者继续服用NAs，393名（31.9%）患者停止服用NAs。继续服用 NAs 被确定为 RFS 的独立风险因素（HR 2.047，95% CI 1.348-3.109，p 结论：这些研究结果表明，HBeAgs 有可能成为治疗 HBeAgs 的新方法：这些研究结果表明，HBeAg阴性、HBsAg血清清除的HBV相关HCC患者有可能在严格监测下停用NAs。
{"title":"Effect of nucleos(t)ide analogue discontinuation on the prognosis of HBeAg-negative hepatitis B virus-related hepatocellular carcinoma after hepatectomy: A propensity score matching analysis","authors":"Ting Sun, Yiwen Qiu, Tao Wang, Yi Yang, Haizhou Qiu, Shu Shen, Huasheng Pang, Wentao Wang","doi":"10.1002/cam4.70185","DOIUrl":"10.1002/cam4.70185","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348–3.109, <i>p</i> < 0.001 before PSM and HR 2.756, 95% CI 1.537–4.942, <i>p</i> < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (<i>p</i> = 0.029 before PSM and <i>p</i> < 0.001 after PSM) and comparable OS (<i>p</i> = 0.935 before PSM and <i>p</i> = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (<i>p</i> for interaction <0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102533","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}
Md. Tobibul Islam, Md Enamul Hoque, Mohammad Ullah, Md. Toufiqul Islam, Nabila Akter Nishu, Md. Rabiul Islam
Objective
Breast cancer is one of the leading cancer causes among women worldwide. It can be classified as invasive ductal carcinoma (IDC) or metastatic cancer. Early detection of breast cancer is challenging due to the lack of early warning signs. Generally, a mammogram is recommended by specialists for screening. Existing approaches are not accurate enough for real-time diagnostic applications and thus require better and smarter cancer diagnostic approaches. This study aims to develop a customized machine-learning framework that will give more accurate predictions for IDC and metastasis cancer classification.
Methods
This work proposes a convolutional neural network (CNN) model for classifying IDC and metastatic breast cancer. The study utilized a large-scale dataset of microscopic histopathological images to automatically perceive a hierarchical manner of learning and understanding.
Results
It is evident that using machine learning techniques significantly (15%–25%) boost the effectiveness of determining cancer vulnerability, malignancy, and demise. The results demonstrate an excellent performance ensuring an average of 95% accuracy in classifying metastatic cells against benign ones and 89% accuracy was obtained in terms of detecting IDC.
Conclusions
The results suggest that the proposed model improves classification accuracy. Therefore, it could be applied effectively in classifying IDC and metastatic cancer in comparison to other state-of-the-art models.
{"title":"CNN-based deep learning approach for classification of invasive ductal and metastasis types of breast carcinoma","authors":"Md. Tobibul Islam, Md Enamul Hoque, Mohammad Ullah, Md. Toufiqul Islam, Nabila Akter Nishu, Md. Rabiul Islam","doi":"10.1002/cam4.70069","DOIUrl":"https://doi.org/10.1002/cam4.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Breast cancer is one of the leading cancer causes among women worldwide. It can be classified as invasive ductal carcinoma (IDC) or metastatic cancer. Early detection of breast cancer is challenging due to the lack of early warning signs. Generally, a mammogram is recommended by specialists for screening. Existing approaches are not accurate enough for real-time diagnostic applications and thus require better and smarter cancer diagnostic approaches. This study aims to develop a customized machine-learning framework that will give more accurate predictions for IDC and metastasis cancer classification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This work proposes a convolutional neural network (CNN) model for classifying IDC and metastatic breast cancer. The study utilized a large-scale dataset of microscopic histopathological images to automatically perceive a hierarchical manner of learning and understanding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It is evident that using machine learning techniques significantly (15%–25%) boost the effectiveness of determining cancer vulnerability, malignancy, and demise. The results demonstrate an excellent performance ensuring an average of 95% accuracy in classifying metastatic cells against benign ones and 89% accuracy was obtained in terms of detecting IDC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results suggest that the proposed model improves classification accuracy. Therefore, it could be applied effectively in classifying IDC and metastatic cancer in comparison to other state-of-the-art models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100464","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}
Guang-Liang Chen, Kai Xue, Qunling Zhang, Zu-guang Xia, Jia Jin, Ran Li, Yizhen Liu, Fangfang Lv, Xiaonan Hong, Xiaoqiu Li, Junning Cao
Background
In relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), a negative prognosis is frequently linked to heightened epigenetic heterogeneity. Chidamide, a selective histone deacetylase inhibitor, shows promise as a targeted therapy for R/R DLBCL by targeting abnormal epigenetic changes associated with poor prognosis.
Methods
A cohort of 27 ineligible patients with R/R DLBCL participated in an open — label, single — arm study. Chidamide was administered orally at a dose of 30 mg twice weekly for one week during the induction monotherapy phase. The subsequent combination therapy phase involved oral chidamide at a dose of 20 mg twice weekly for two weeks, followed by a one-week discontinuation period, in conjunction with intravenous R-GDP every 21 days.
Results
Among the cohort of 31 patients who underwent screening (median age: 67 years), 27 were ultimately included in the study, with 14 individuals successfully completing six cycles of C-R-GDP treatment. The overall best objective response rate was determined to be 79.1% (95% CI: 75.1%–83.3%), comprising a complete response rate of 45.8% (95% CI: 41.6%–49.9%) and a partial response rate of 33.3% (95% CI: 29.3%–37.4%). Within the subgroup of 14 patients who completed the full treatment regimen, the best objective response rate reached 100%, with 71.4% achieving complete response (n = 10) and 28.6% achieving partial response (n = 4). The median follow-up period for these patients was 17.0 months, ranging from 3.5 to 55 months. Progression-free survival was 5.9 months and overall survival was 48.3 months. Anemia was the most common adverse event, affecting all patients. Thrombocytopenia led to treatment interruption or dose reduction in 13 patients. Other common adverse events included hypocalcemia, hyponatremia, and hypokalemia. Three patients experienced grade 3 pneumonitis and one had grade 3 skin rash.
Conclusions
Chidamide combined with R-GDP is a safe and effective treatment option for patients with R/R DLBCL who are not eligible for autologous stem cell transplantation.
{"title":"Chidamide plus R-GDP for relapsed/refractory diffuse large B-cell lymphoma in patients ineligible for autologous transplantation: A prospective, single-arm, phase II study","authors":"Guang-Liang Chen, Kai Xue, Qunling Zhang, Zu-guang Xia, Jia Jin, Ran Li, Yizhen Liu, Fangfang Lv, Xiaonan Hong, Xiaoqiu Li, Junning Cao","doi":"10.1002/cam4.70142","DOIUrl":"https://doi.org/10.1002/cam4.70142","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), a negative prognosis is frequently linked to heightened epigenetic heterogeneity. Chidamide, a selective histone deacetylase inhibitor, shows promise as a targeted therapy for R/R DLBCL by targeting abnormal epigenetic changes associated with poor prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort of 27 ineligible patients with R/R DLBCL participated in an open — label, single — arm study. Chidamide was administered orally at a dose of 30 mg twice weekly for one week during the induction monotherapy phase. The subsequent combination therapy phase involved oral chidamide at a dose of 20 mg twice weekly for two weeks, followed by a one-week discontinuation period, in conjunction with intravenous R-GDP every 21 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the cohort of 31 patients who underwent screening (median age: 67 years), 27 were ultimately included in the study, with 14 individuals successfully completing six cycles of C-R-GDP treatment. The overall best objective response rate was determined to be 79.1% (95% CI: 75.1%–83.3%), comprising a complete response rate of 45.8% (95% CI: 41.6%–49.9%) and a partial response rate of 33.3% (95% CI: 29.3%–37.4%). Within the subgroup of 14 patients who completed the full treatment regimen, the best objective response rate reached 100%, with 71.4% achieving complete response (<i>n</i> = 10) and 28.6% achieving partial response (<i>n</i> = 4). The median follow-up period for these patients was 17.0 months, ranging from 3.5 to 55 months. Progression-free survival was 5.9 months and overall survival was 48.3 months. Anemia was the most common adverse event, affecting all patients. Thrombocytopenia led to treatment interruption or dose reduction in 13 patients. Other common adverse events included hypocalcemia, hyponatremia, and hypokalemia. Three patients experienced grade 3 pneumonitis and one had grade 3 skin rash.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Chidamide combined with R-GDP is a safe and effective treatment option for patients with R/R DLBCL who are not eligible for autologous stem cell transplantation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100307","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}
First-line osimertinib plus chemotherapy significantly prolonged progression-free survival of patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) compared to osimertinib, according to the FLAURA2 trial.
Methods
We established a Markov model to compare the cost-effectiveness of osimertinib plus chemotherapy with that of osimertinib alone. Clinical data were obtained from the FLAURA and FLAURA2 trials, and additional data were extracted from online resources and publications. Sensitivity analyses were conducted to evaluate the robustness of the findings. We used A willingness-to-pay threshold of $150,000 per quality-adjusted life-years (QALYs) gained. The main outcomes were QALYs, overall costs, incremental cost-effectiveness ratio (ICER), incremental net monetary benefit, and incremental net health benefit. Subgroup analyses were conducted according to patients' mutation type and central nervous system (CNS) metastatic status.
Results
In a 20-year time horizon, the ICER of osimertinib plus chemotherapy versus osimertinib alone was $223,727.1 per QALY gained. The sensitivity analyses identified the cost of osimertinib and the hazard ratio for overall survival as the top 2 influential factors and a 1.9% probability of osimertinib plus chemotherapy to be cost-effective. The subgroup analyses revealed ICERs of $132,614.1, $224,449.8, $201,464.1, and $130,159.7 per QALY gained for L858R mutations, exon 19 deletions, CNS metastases, and no CNS metastases subgroups, respectively.
Conclusions
From the perspective of the United States health care system, osimertinib plus chemotherapy is not cost-effective compared to osimertinib alone for treatment-naïve patients with EGFR-mutated advanced NSCLC, but more favorable cost-effectiveness occurs in patients with L858R mutations and patients without baseline CNS metastases.
{"title":"Cost-effectiveness analysis of osimertinib plus chemotherapy for patients with EGFR-mutated advanced non-small cell lung cancer","authors":"Wentao Tian, Lishui Niu, Rongrong Zhou, Ziqi Wang, Jiaoyang Ning, Ruoyu Lu, Yin Shi, Zhaohua Tan","doi":"10.1002/cam4.70083","DOIUrl":"https://doi.org/10.1002/cam4.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>First-line osimertinib plus chemotherapy significantly prolonged progression-free survival of patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) compared to osimertinib, according to the FLAURA2 trial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We established a Markov model to compare the cost-effectiveness of osimertinib plus chemotherapy with that of osimertinib alone. Clinical data were obtained from the FLAURA and FLAURA2 trials, and additional data were extracted from online resources and publications. Sensitivity analyses were conducted to evaluate the robustness of the findings. We used A willingness-to-pay threshold of $150,000 per quality-adjusted life-years (QALYs) gained. The main outcomes were QALYs, overall costs, incremental cost-effectiveness ratio (ICER), incremental net monetary benefit, and incremental net health benefit. Subgroup analyses were conducted according to patients' mutation type and central nervous system (CNS) metastatic status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In a 20-year time horizon, the ICER of osimertinib plus chemotherapy versus osimertinib alone was $223,727.1 per QALY gained. The sensitivity analyses identified the cost of osimertinib and the hazard ratio for overall survival as the top 2 influential factors and a 1.9% probability of osimertinib plus chemotherapy to be cost-effective. The subgroup analyses revealed ICERs of $132,614.1, $224,449.8, $201,464.1, and $130,159.7 per QALY gained for L858R mutations, exon 19 deletions, CNS metastases, and no CNS metastases subgroups, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>From the perspective of the United States health care system, osimertinib plus chemotherapy is not cost-effective compared to osimertinib alone for treatment-naïve patients with EGFR-mutated advanced NSCLC, but more favorable cost-effectiveness occurs in patients with L858R mutations and patients without baseline CNS metastases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100306","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}
Baoluhe Zhang, Bao Jin, Xiang'an Wu, Jiali Xing, Xiao Liu, Xueshuai Wan, Haifeng Xu, Yiyao Xu, Yilei Mao, Qian Chen, Yating Bai, Mei Guan, Shunda Du
Background
This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA).
Methods and Results
The transcriptomic and whole-exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression-free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (p = 0.0287) and upregulation of genes associated with cancer-related transcriptional misregulation, chemokine signaling, and cytokine-cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (p = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer-related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti-tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients.
Conclusions
In this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi-omics analysis.
背景 本研究探讨了与胆管癌（CCA）较好预后相关的分子特征。 方法和结果 分析了 70 例配对组织的转录组和全外显子组测序数据，并根据无进展生存期（PFS）、分化程度和淋巴结转移情况对患者进行分组。在 70 例患者中，TP53 基因突变频率最高（53%），而 FLG 基因突变仅发生在长无进展生存期组。在长生存期组和短生存期组的比较中，短生存期组的单核细胞浸润水平更高（p = 0.0287），与癌症相关的转录失调、趋化因子信号转导和细胞因子-细胞因子受体相互作用相关的基因上调。不同分化组和淋巴结转移组的免疫细胞浸润和基因表达差异显著。尤其值得注意的是，淋巴结转移组的 CD8 T 细胞和 NK 细胞浸润明显增加（p = 0.0291，0.0459），对预后有显著影响。此外，与铂类抗性、Th17 细胞分化、Th1 和 Th2 细胞分化途径相关的基因在该组中过度表达。总之，短PFS组的单核细胞浸润水平较高，与癌症相关通路的相关基因表达升高，这表明预后较差。CD8 T 细胞和 NK 细胞浸润的明显增加反映了抗肿瘤免疫反应的增强，强调了免疫浸润水平和基因表达在预测 CCA 患者预后中的相关性。 结论 本研究通过全面的多组学分析，阐明了影响 CCA 预后的相关分子机制和通路。
{"title":"Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma","authors":"Baoluhe Zhang, Bao Jin, Xiang'an Wu, Jiali Xing, Xiao Liu, Xueshuai Wan, Haifeng Xu, Yiyao Xu, Yilei Mao, Qian Chen, Yating Bai, Mei Guan, Shunda Du","doi":"10.1002/cam4.70135","DOIUrl":"https://doi.org/10.1002/cam4.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>The transcriptomic and whole-exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression-free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (<i>p</i> = 0.0287) and upregulation of genes associated with cancer-related transcriptional misregulation, chemokine signaling, and cytokine-cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (<i>p</i> = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer-related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti-tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi-omics analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100308","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}
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