Lin Chen, Yuan Hu, Bohao Zheng, Limei Luo, Zhenzhen Su
Background
T cells, the “superstar” of the immune system, play a crucial role in antitumor immunity. T-cell receptors (TCR) are crucial molecules that enable T cells to identify antigens and start immunological responses. The body has evolved a unique method for rearrangement, resulting in a vast diversity of TCR repertoires. A healthy TCR repertoire is essential for the particular identification of antigens by T cells.
Methods
In this article, we systematically summarized the TCR creation mechanisms and analysis methodologies, particularly focusing on the application of next-generation sequencing (NGS) technology. We explore the TCR repertoire in health and cancer, and discuss the implications of TCR repertoire analysis in understanding carcinogenesis, cancer progression, and treatment.
Results
The TCR repertoire analysis has enormous potential for monitoring the emergence and progression of malignancies, as well as assessing therapy response and prognosis. The application of NGS has dramatically accelerated our comprehension of TCR diversity and its role in cancer immunity.
Conclusions
To substantiate the significance of TCR repertoires as biomarkers, more thorough and exhaustive research should be conducted. The TCR repertoire analysis, enabled by advanced sequencing technologies, is poised to become a crucial tool in the future of cancer diagnosis, monitoring, and therapy evaluation.
{"title":"Human TCR repertoire in cancer","authors":"Lin Chen, Yuan Hu, Bohao Zheng, Limei Luo, Zhenzhen Su","doi":"10.1002/cam4.70164","DOIUrl":"10.1002/cam4.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>T cells, the “superstar” of the immune system, play a crucial role in antitumor immunity. T-cell receptors (TCR) are crucial molecules that enable T cells to identify antigens and start immunological responses. The body has evolved a unique method for rearrangement, resulting in a vast diversity of TCR repertoires. A healthy TCR repertoire is essential for the particular identification of antigens by T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this article, we systematically summarized the TCR creation mechanisms and analysis methodologies, particularly focusing on the application of next-generation sequencing (NGS) technology. We explore the TCR repertoire in health and cancer, and discuss the implications of TCR repertoire analysis in understanding carcinogenesis, cancer progression, and treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The TCR repertoire analysis has enormous potential for monitoring the emergence and progression of malignancies, as well as assessing therapy response and prognosis. The application of NGS has dramatically accelerated our comprehension of TCR diversity and its role in cancer immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>To substantiate the significance of TCR repertoires as biomarkers, more thorough and exhaustive research should be conducted. The TCR repertoire analysis, enabled by advanced sequencing technologies, is poised to become a crucial tool in the future of cancer diagnosis, monitoring, and therapy evaluation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138762","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}
Tobias Max Philipp Hartwich, Miranda Mansolf, Cem Demirkiran, Michelle Greenman, Stefania Bellone, Blair McNamara, Shuvro P. Nandi, Ludmil B. Alexandrov, Yang Yang-Hartwich, Silvia Coma, Jonathan Pachter, Alessandro D. Santin
Background
High-grade endometrial cancers (EAC) are aggressive tumors with a high risk of progression after treatment. As EAC may harbor mutations in the RAS/MAPK pathways, we evaluated the preclinical in vitro and in vivo efficacy of avutometinib, a RAF/MEK clamp, in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718, against multiple primary EAC cell lines and xenografts.
Methods
Whole-exome sequencing (WES) was used to evaluate the genetic landscape of five primary EAC cell lines. The in vitro activity of avutometinib and defactinib as single agents and in combination was evaluated using cell viability, cell cycle, and cytotoxicity assays. Mechanistic studies were performed using Western blot assays while in vivo experiments were completed in UTE10 engrafted mice treated with either vehicle, avutometinib, VS-4718, or their combination through oral gavage.
Results
WES results demonstrated multiple EAC cell lines to harbor genetic derangements in the RAS/MAPK pathway including KRAS/PTEN/PIK3CA/BRAF/ARID1A, potentially sensitizing to FAK and RAF/MEK inhibition. Five out of five of the EAC cell lines demonstrated in vitro sensitivity to FAK and/or RAF/MEK inhibition. By Western blot assays, exposure of EAC cell lines to defactinib, avutometinib, and their combination demonstrated decreased phosphorylated FAK (p-FAK) as well as decreased p-MEK and p-ERK. In vivo the combination of avutometinib/VS-4718 demonstrated superior tumor growth inhibition compared to single-agent treatment and controls starting at Day 9 (p < 0.02 and p < 0.04) in UTE10 xenografts.
Conclusions
Avutometinib, defactinib, and to a larger extent their combinations, demonstrated promising in vitro and in vivo activity against EAC cell lines and xenografts. These preclinical data support the potential clinical evaluation of this combination in high-grade EAC patients.
{"title":"Preclinical evaluation of avutometinib and defactinib in high-grade endometrioid endometrial cancer","authors":"Tobias Max Philipp Hartwich, Miranda Mansolf, Cem Demirkiran, Michelle Greenman, Stefania Bellone, Blair McNamara, Shuvro P. Nandi, Ludmil B. Alexandrov, Yang Yang-Hartwich, Silvia Coma, Jonathan Pachter, Alessandro D. Santin","doi":"10.1002/cam4.70210","DOIUrl":"10.1002/cam4.70210","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High-grade endometrial cancers (EAC) are aggressive tumors with a high risk of progression after treatment. As EAC may harbor mutations in the RAS/MAPK pathways, we evaluated the preclinical in vitro and in vivo efficacy of avutometinib, a RAF/MEK clamp, in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718, against multiple primary EAC cell lines and xenografts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-exome sequencing (WES) was used to evaluate the genetic landscape of five primary EAC cell lines. The in vitro activity of avutometinib and defactinib as single agents and in combination was evaluated using cell viability, cell cycle, and cytotoxicity assays. Mechanistic studies were performed using Western blot assays while in vivo experiments were completed in UTE10 engrafted mice treated with either vehicle, avutometinib, VS-4718, or their combination through oral gavage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>WES results demonstrated multiple EAC cell lines to harbor genetic derangements in the RAS/MAPK pathway including KRAS/PTEN/PIK3CA/BRAF/ARID1A, potentially sensitizing to FAK and RAF/MEK inhibition. Five out of five of the EAC cell lines demonstrated in vitro sensitivity to FAK and/or RAF/MEK inhibition. By Western blot assays, exposure of EAC cell lines to defactinib, avutometinib, and their combination demonstrated decreased phosphorylated FAK (p-FAK) as well as decreased p-MEK and p-ERK. In vivo the combination of avutometinib/VS-4718 demonstrated superior tumor growth inhibition compared to single-agent treatment and controls starting at Day 9 (<i>p</i> < 0.02 and <i>p</i> < 0.04) in UTE10 xenografts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Avutometinib, defactinib, and to a larger extent their combinations, demonstrated promising in vitro and in vivo activity against EAC cell lines and xenografts. These preclinical data support the potential clinical evaluation of this combination in high-grade EAC patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138764","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}
Si Chen, Caihong Yao, Na Tian, Chunying Zhang, Yuemei Chen, Xuting Wang, Yue Jiang, Tonghao Zhang, Tingting Zeng, Yali Song
Background
Chronic infections by pathogenic microorganisms play a significant role in cancer development, disrupting the body's immune system and microenvironment. This interference impairs the body's ability to eliminate these microorganisms promptly, allowing them to persist by evading immune defenses.
Aims
This study aimed to explore how chronic pathogenic infections influence the immune microenvironment, impacting tumorigenesis, cancer progression, and treatment strategies. Additionally, it seeks to investigate the effects of these infections on specific immune checkpoints and identify potential targets for immunotherapy.
Methods
We conducted searches, readings, and detailed analyses of key terms in databases like PubMed and Web of Science to evaluate the impact of chronic infections by pathogenic microorganisms on the immune microenvironment.
Results
Our analysis demonstrates a significant association between persistent chronic infections by pathogenic microorganisms and tumorigenesis. Notable impacts on the immune microenvironment include changes in immune cell function and the regulation of immune checkpoints, offering insights into potential targets for cancer immunotherapy.
Discussion
This study highlights the complex relationship between chronic infections and cancer development, presenting new opportunities for cancer immunotherapy by understanding their effects on the immune microenvironment. The influence of these infections on immune checkpoints emphasizes the crucial role of the immune system in cancer treatment.
Conclusion
Chronic infections by pathogenic microorganisms greatly affect the immune microenvironment, tumorigenesis, and cancer treatment. Unraveling the underlying mechanisms can unveil potential targets for immunotherapy, improving our comprehension of the immune response to cancer and potentially leading to more effective cancer treatments in the future.
背景：病原微生物的慢性感染在癌症发展中起着重要作用，它干扰了机体的免疫系统和微环境。目的：本研究旨在探讨慢性病原体感染如何影响免疫微环境，从而影响肿瘤发生、癌症进展和治疗策略。此外，它还试图研究这些感染对特定免疫检查点的影响，并确定免疫疗法的潜在靶点：我们对 PubMed 和 Web of Science 等数据库中的关键术语进行了检索、阅读和详细分析，以评估病原微生物慢性感染对免疫微环境的影响：结果：我们的分析表明，病原微生物的持续慢性感染与肿瘤发生之间存在显著关联。对免疫微环境的显著影响包括免疫细胞功能的变化和免疫检查点的调控，为癌症免疫疗法的潜在靶点提供了启示：本研究强调了慢性感染与癌症发展之间的复杂关系，通过了解它们对免疫微环境的影响，为癌症免疫疗法提供了新的机遇。这些感染对免疫检查点的影响强调了免疫系统在癌症治疗中的关键作用：病原微生物的慢性感染对免疫微环境、肿瘤发生和癌症治疗有很大影响。揭示其潜在机制可以发现免疫疗法的潜在靶点，从而提高我们对癌症免疫反应的理解，并有可能在未来找到更有效的癌症治疗方法。
{"title":"The interplay between persistent pathogen infections with tumor microenvironment and immunotherapy in cancer","authors":"Si Chen, Caihong Yao, Na Tian, Chunying Zhang, Yuemei Chen, Xuting Wang, Yue Jiang, Tonghao Zhang, Tingting Zeng, Yali Song","doi":"10.1002/cam4.70154","DOIUrl":"10.1002/cam4.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic infections by pathogenic microorganisms play a significant role in cancer development, disrupting the body's immune system and microenvironment. This interference impairs the body's ability to eliminate these microorganisms promptly, allowing them to persist by evading immune defenses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to explore how chronic pathogenic infections influence the immune microenvironment, impacting tumorigenesis, cancer progression, and treatment strategies. Additionally, it seeks to investigate the effects of these infections on specific immune checkpoints and identify potential targets for immunotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted searches, readings, and detailed analyses of key terms in databases like PubMed and Web of Science to evaluate the impact of chronic infections by pathogenic microorganisms on the immune microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis demonstrates a significant association between persistent chronic infections by pathogenic microorganisms and tumorigenesis. Notable impacts on the immune microenvironment include changes in immune cell function and the regulation of immune checkpoints, offering insights into potential targets for cancer immunotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This study highlights the complex relationship between chronic infections and cancer development, presenting new opportunities for cancer immunotherapy by understanding their effects on the immune microenvironment. The influence of these infections on immune checkpoints emphasizes the crucial role of the immune system in cancer treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Chronic infections by pathogenic microorganisms greatly affect the immune microenvironment, tumorigenesis, and cancer treatment. Unraveling the underlying mechanisms can unveil potential targets for immunotherapy, improving our comprehension of the immune response to cancer and potentially leading to more effective cancer treatments in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138766","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}
Currently, creating more effector T cells and augmenting their functions is a focal point in pancreatic ductal adenocarcinoma (PDAC) treatment research. T cell immunoglobulin domain and mucin domain molecule 4 (TIM-4), known for promoting cancer progression in various malignancies, is implicated in the suppressive immune microenvironment of tumors. Analyzing of the role of TIM-4 in the immune regulation of PDAC can offer novel insights for immune therapy.
Methods
We analyzed the TIM-4 expression in tumor specimens from PDAC patients. Meanwhile, multiple fluorescent immunohistochemical staining was used to study the distribution characteristics of TIM-4, and through tissue microarrays, we explored its correlation with patient prognosis. The influence of TIM-4 overexpression on cell function was analyzed using RNA-seq. Flow cytometry and ELISA were used for verification. Finally, the relationship between TIM-4 and T lymphocytes was analyzed by tissue microarray, and the impacts of TIM-4 on T cell subsets were observed by cell coculture technology and a mouse pancreatic cancer in situ model.
Results
In PDAC, TIM-4 is mainly expressed in tumor cells and negatively correlated with patient prognosis. TIM-4 influences the differentiation of Treg by inhibiting IL-6 secretion in pancreatic cancer cells and facilitates the proliferation of pancreatic cancer in mice. Additionally, the mechanism may be through the CD8+ effector T cells (CD8+Tc).
Conclusion
TIM-4 has the potential to be an immunotherapeutic target or to improve the efficacy of chemotherapy for PDAC.
{"title":"TIM-4 increases the proportion of CD4+CD25+FOXP3+ regulatory T cells in the pancreatic ductal adenocarcinoma microenvironment by inhibiting IL-6 secretion","authors":"Ziyao Wang, Zerong Xie, Yu Mou, Ruiman Geng, Chen Chen, Nengwen Ke","doi":"10.1002/cam4.70110","DOIUrl":"10.1002/cam4.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Currently, creating more effector T cells and augmenting their functions is a focal point in pancreatic ductal adenocarcinoma (PDAC) treatment research. T cell immunoglobulin domain and mucin domain molecule 4 (TIM-4), known for promoting cancer progression in various malignancies, is implicated in the suppressive immune microenvironment of tumors. Analyzing of the role of TIM-4 in the immune regulation of PDAC can offer novel insights for immune therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed the TIM-4 expression in tumor specimens from PDAC patients. Meanwhile, multiple fluorescent immunohistochemical staining was used to study the distribution characteristics of TIM-4, and through tissue microarrays, we explored its correlation with patient prognosis. The influence of TIM-4 overexpression on cell function was analyzed using RNA-seq. Flow cytometry and ELISA were used for verification. Finally, the relationship between TIM-4 and T lymphocytes was analyzed by tissue microarray, and the impacts of TIM-4 on T cell subsets were observed by cell coculture technology and a mouse pancreatic cancer in situ model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In PDAC, TIM-4 is mainly expressed in tumor cells and negatively correlated with patient prognosis. TIM-4 influences the differentiation of Treg by inhibiting IL-6 secretion in pancreatic cancer cells and facilitates the proliferation of pancreatic cancer in mice. Additionally, the mechanism may be through the CD8<sup>+</sup> effector T cells (CD8<sup>+</sup>Tc).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TIM-4 has the potential to be an immunotherapeutic target or to improve the efficacy of chemotherapy for PDAC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131362","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}
Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high-risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively.
Methods
In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the β-value of the corresponding regression coefficient. A predictive risk-scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21-involved risk with the established R-ISS and R2-ISS models.
Results
Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p < 0.05), which could be effectively mitigated by ASCT. The +1q21-involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no-ASCT, and TP53 deletion. This model, termed the ultra-high-risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R-ISS stage 3 and R2-ISS stage 4.
Conclusion
The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.
{"title":"A predictive risk-scoring model for survival prognosis of multiple myeloma based on gain/amplification of 1q21: Experience in a tertiary hospital in South-Western China","authors":"Yanqiu Xiong, Shanshan Liang, Wenjiao Tang, Li Zhang, Yuhuan Zheng, Ling Pan, Ting Niu","doi":"10.1002/cam4.70193","DOIUrl":"10.1002/cam4.70193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high-risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, <i>n</i> = 244) and a validation set (33.5%, <i>n</i> = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the β-value of the corresponding regression coefficient. A predictive risk-scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21-involved risk with the established R-ISS and R2-ISS models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (<i>p</i> < 0.05), which could be effectively mitigated by ASCT. The +1q21-involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no-ASCT, and TP53 deletion. This model, termed the ultra-high-risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R-ISS stage 3 and R2-ISS stage 4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131354","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}
Shuwen Han, Jing Zhuang, Yifei Song, Xinyue Wu, Xiaojian Yu, Ye Tao, Jian Chu, Zhanbo Qu, Yinhang Wu, Shugao Han, Xi Yang
Background
Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics.
Objective
To develop gut bacterial subtypes and explore potential microbial targets for CRC.
Methods
Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC-associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA).
Results
Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were Escherichia-Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. Bacilli, Lactobacillales, etc., were positively correlated with subtype B. Positive correlation of Blautia, Lachnospiraceae, etc., with subtype C and negative correlation of Coriobacteriia, Coriobacteriales, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes.
Conclusion
Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.
背景：肠道细菌与结直肠癌（CRC）及其临床病理特征有关：肠道细菌与结直肠癌（CRC）及其临床病理特征有关：方法：采集 914 名志愿者（376 名 CRC、363 名晚期腺癌患者）的粪便样本：方法：对 914 名志愿者（376 名 CRC 患者、363 名晚期腺瘤患者和 175 名正常对照者）的粪便样本进行 16S rRNA 测序。利用无监督学习生成肠道微生物亚型。绘制了肠道细菌群落组成图和聚类效应图。分析了肠道细菌丰度的差异。然后，评估了 CRC 相关细菌与亚型的关联以及肠道细菌与临床信息的关联。基于肠道差异细菌构建的 CatBoost 模型可识别包括 CRC 和晚期腺瘤（AA）在内的疾病：结果：通过无监督学习，最终获得了四种肠道微生物亚型（A、B、C、D）。各亚型的特征细菌分别为 A 亚型的埃希氏-志贺氏菌、B 亚型的链球菌、C 亚型的布劳氏菌和 D 亚型的乳杆菌。临床信息（如游离脂肪酸和总胆固醇）和 CRC 病理信息（如肿瘤深度）在不同的肠道微生物亚型之间存在差异。发现芽孢杆菌、乳酸杆菌等与 B 亚型呈正相关，而 Blautia、Lachnospiraceae 等与 C 亚型呈正相关，Coriobacteriia、Coriobacteriales 等与 D 亚型呈负相关。最后，基于肠道微生物亚型的 CatBoost 模型提高了对 CRC 鉴定的预测能力：结论：肠道微生物亚型提供了特征性肠道细菌，有望为诊断 CRC 做出贡献。
{"title":"Gut microbial subtypes and clinicopathological value for colorectal cancer","authors":"Shuwen Han, Jing Zhuang, Yifei Song, Xinyue Wu, Xiaojian Yu, Ye Tao, Jian Chu, Zhanbo Qu, Yinhang Wu, Shugao Han, Xi Yang","doi":"10.1002/cam4.70180","DOIUrl":"10.1002/cam4.70180","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To develop gut bacterial subtypes and explore potential microbial targets for CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC-associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were <i>Escherichia-Shigella</i> in subtype A, <i>Streptococcus</i> in subtype B, <i>Blautia</i> in subtype C, and <i>Bacteroides</i> in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. <i>Bacilli</i>, <i>Lactobacillales</i>, etc., were positively correlated with subtype B. Positive correlation of <i>Blautia</i>, <i>Lachnospiraceae</i>, etc., with subtype C and negative correlation of <i>Coriobacteriia</i>, <i>Coriobacteriales</i>, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131356","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}
Eduardo Terán, Rebeca Lozano, César A. Rodríguez, Mar Abad, Luis Figuero, José Antonio Muñoz, Belén Cigarral, Aline Rodrígues, Magdalena Sancho, M. Asunción Gómez, Daniel Morchón, Juan Carlos Montero, José María Sayagués, M. Dolores Ludeña, Emilio Fonseca
Introduction
Hotspots (HS) mutations in the PIK3CA gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early-stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma approaches and to analyze the prognostic impact of PIK3CA mutations (PIK3CAm) in HR+/HER2− BC.
Methods
A retrospective and unicentric analysis of PIK3CA mutational status in tissue and plasma samples by Cobas®PIK3CA Mutation Kit in patients with HR+/HER2− BC.
Results
We analyzed 225 samples from 161 patients with luminal BC. PIK3CA mutations were identified in 62 patients (38.5%), of which 39.6% were found in tissue and 11.8% in plasma. In advanced disease, plasma and tissue correlation rate was performed in 64 cases, with an overall agreement of 70.3%. Eighty patients were treated with CDK4/6 inhibitors + endocrine therapy. We observed a moderately worse progression-free survival (PFS) in PIK3CAm versus wild-type (WT) (24 m vs. 30 m; HR = 1.39, p = 0.26). A subanalysis was carried out based on exons 9 and 20, which showed a statistically poorer PFS in PIK3CAm exon 9 versus 20 population (9.7 m vs. 30.3 m; HR = 2.84; p = 0.024). Furthermore, detection of PIK3CAm in plasma was linked to a worse PFS vs PIK3CAm detection just in tissue (12.4 vs. 29.3; HR = 2.4; p = 0.08).
Conclusions
Our findings suggest the PIK3CA evaluation in tissue as the diagnostic method of choice, however, additional investigations are required to improve the role of liquid biopsy in the PIK3CA assessment. PIK3CAm show worse outcomes in advanced luminal BC, especially in exon 9 mutation carriers, despite visceral involvement, prior exposure to endocrine therapy or detection of PIK3CAm in plasma, with an unclear prognosis in early-stage disease. Nonetheless, this should be validated in a prospective cohort study.
导言：PIK3CA 基因的热点（HS）突变可能会导致晚期乳腺癌（BC）较差的肿瘤预后和内分泌抵抗，但它们在早期疾病中的预后作用仍存在争议。血浆和组织方法的总体一致性尚未得到很好的探讨。我们的目的是将组织和血浆方法联系起来，分析PIK3CA突变（PIK3CAm）对HR+/HER2- BC预后的影响：用Cobas®PIK3CA突变试剂盒对HR+/HER2- BC患者组织和血浆样本中的PIK3CA突变状态进行回顾性和单中心分析：我们分析了来自161名腔隙性BC患者的225份样本。在62名患者（38.5%）中发现了PIK3CA突变，其中39.6%在组织中发现，11.8%在血浆中发现。在晚期疾病中，64 例患者进行了血浆和组织相关性分析，总体一致率为 70.3%。80例患者接受了CDK4/6抑制剂+内分泌治疗。我们观察到，PIK3CAm与野生型（WT）相比，无进展生存期（PFS）略差（24 m vs. 30 m; HR = 1.39, p = 0.26）。根据外显子9和20进行的子分析显示，PIK3CAm外显子9与20人群的PFS在统计学上较差（9.7 m vs. 30.3 m; HR = 2.84; p = 0.024）。此外，在血浆中检测到PIK3CAm与仅在组织中检测到PIK3CAm相比，PFS更差（12.4 vs. 29.3; HR = 2.4; p = 0.08）：我们的研究结果表明，组织中的PIK3CA评估是首选的诊断方法，但是还需要进行更多的研究，以提高液体活检在PIK3CA评估中的作用。PIK3CAm在晚期腔隙性BC中显示出更差的预后，尤其是在外显子9突变携带者中，尽管有内脏受累、之前接受过内分泌治疗或在血浆中检测到PIK3CAm，但早期疾病的预后尚不明确。不过，这一点应在前瞻性队列研究中得到验证。
{"title":"PIK3CA mutational status in tissue and plasma as a prognostic biomarker in HR+/HER2− breast cancer","authors":"Eduardo Terán, Rebeca Lozano, César A. Rodríguez, Mar Abad, Luis Figuero, José Antonio Muñoz, Belén Cigarral, Aline Rodrígues, Magdalena Sancho, M. Asunción Gómez, Daniel Morchón, Juan Carlos Montero, José María Sayagués, M. Dolores Ludeña, Emilio Fonseca","doi":"10.1002/cam4.70101","DOIUrl":"10.1002/cam4.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hotspots (HS) mutations in the <i>PIK3CA</i> gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early-stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma approaches and to analyze the prognostic impact of <i>PIK3CA</i> mutations (<i>PIK3CAm</i>) in HR+/HER2− BC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective and unicentric analysis of <i>PIK3CA</i> mutational status in tissue and plasma samples by Cobas®PIK3CA Mutation Kit in patients with HR+/HER2− BC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analyzed 225 samples from 161 patients with luminal BC. <i>PIK3CA</i> mutations were identified in 62 patients (38.5%), of which 39.6% were found in tissue and 11.8% in plasma. In advanced disease, plasma and tissue correlation rate was performed in 64 cases, with an overall agreement of 70.3%. Eighty patients were treated with CDK4/6 inhibitors + endocrine therapy. We observed a moderately worse progression-free survival (PFS) in <i>PIK3CAm</i> versus wild-type (WT) (24 m vs. 30 m; HR = 1.39, <i>p</i> = 0.26). A subanalysis was carried out based on exons 9 and 20, which showed a statistically poorer PFS in <i>PIK3CAm</i> exon 9 versus 20 population (9.7 m vs. 30.3 m; HR = 2.84; <i>p</i> = 0.024). Furthermore, detection of <i>PIK3CAm</i> in plasma was linked to a worse PFS vs <i>PIK3CAm</i> detection just in tissue (12.4 vs. 29.3; HR = 2.4; <i>p</i> = 0.08).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest the <i>PIK3CA</i> evaluation in tissue as the diagnostic method of choice, however, additional investigations are required to improve the role of liquid biopsy in the <i>PIK3CA</i> assessment. <i>PIK3CAm</i> show worse outcomes in advanced luminal BC, especially in exon 9 mutation carriers, despite visceral involvement, prior exposure to endocrine therapy or detection of <i>PIK3CAm</i> in plasma, with an unclear prognosis in early-stage disease. Nonetheless, this should be validated in a prospective cohort study.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131358","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}
Erin E. Kent, Kelly R. Tan, Zev M. Nakamura, Jesse Kovacs, Mindy Gellin, Allison Deal, Eliza M. Park, Maija Reblin
Introduction
Rural cancer caregivers experience obstacles in accessing services, obtaining respite, and ensuring their care recipients receive quality care. These challenges warrant opportunities to participate in evidence-based behavioral intervention trials to fill support gaps. Adaptation to rural settings can facilitate appropriate fit, given higher caregiver service needs and unique challenges. We present findings from the adaptation process of a psychoeducational intervention designed to support cancer caregivers in rural settings.
Methods
We adapted Reblin's CARING intervention, designed for neuro-oncology, to target caregivers of rural cancer patients across cancer sites. First, we conducted formative work to determine the unmet social and supportive care needs rural cancer caregivers faced. We used the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) to guide the modifications. To conduct the adaptation, we elicited feedback through qualitative interviews of seven caregivers and three cancer hospital staff and thematic analysis to inform intervention modifications. Our qualitative study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ).
Results
Interviews revealed that service access was a pressing need, along with financial (e.g., treatment costs, employment challenges) and geographic barriers (e.g., distance to treatment, road conditions). We modified content, training, and context using the FRAME-IS steps. Changes enhanced fit through the following adaptations: changes to social support domains, session content, interventionist training, resource offerings, screening and recruitment processes, and virtual delivery.
Discussion
Challenges to establishing successful psychosocial oncology interventions may be improved through participant-centered approaches and implementation science. Additional systemic challenges, including lack of systematic documentation of caregivers, persist and may especially disadvantage under-represented and underserved groups, such as rural dwellers. The enCompass intervention is undergoing ongoing single-arm pilot of rural cancer patient/caregiver dyads targeting caregiver coping self-efficacy and patient/caregiver distress (Clinical Trials #NCT05828927).
{"title":"Building on and tailoring to: Adapting a cancer caregiver psychoeducational intervention for rural settings","authors":"Erin E. Kent, Kelly R. Tan, Zev M. Nakamura, Jesse Kovacs, Mindy Gellin, Allison Deal, Eliza M. Park, Maija Reblin","doi":"10.1002/cam4.70187","DOIUrl":"10.1002/cam4.70187","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Rural cancer caregivers experience obstacles in accessing services, obtaining respite, and ensuring their care recipients receive quality care. These challenges warrant opportunities to participate in evidence-based behavioral intervention trials to fill support gaps. Adaptation to rural settings can facilitate appropriate fit, given higher caregiver service needs and unique challenges. We present findings from the adaptation process of a psychoeducational intervention designed to support cancer caregivers in rural settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We adapted Reblin's CARING intervention, designed for neuro-oncology, to target caregivers of rural cancer patients across cancer sites. First, we conducted formative work to determine the unmet social and supportive care needs rural cancer caregivers faced. We used the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) to guide the modifications. To conduct the adaptation, we elicited feedback through qualitative interviews of seven caregivers and three cancer hospital staff and thematic analysis to inform intervention modifications. Our qualitative study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Interviews revealed that service access was a pressing need, along with financial (e.g., treatment costs, employment challenges) and geographic barriers (e.g., distance to treatment, road conditions). We modified content, training, and context using the FRAME-IS steps. Changes enhanced fit through the following adaptations: changes to social support domains, session content, interventionist training, resource offerings, screening and recruitment processes, and virtual delivery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Challenges to establishing successful psychosocial oncology interventions may be improved through participant-centered approaches and implementation science. Additional systemic challenges, including lack of systematic documentation of caregivers, persist and may especially disadvantage under-represented and underserved groups, such as rural dwellers. The enCompass intervention is undergoing ongoing single-arm pilot of rural cancer patient/caregiver dyads targeting caregiver coping self-efficacy and patient/caregiver distress (Clinical Trials #NCT05828927).</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131355","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}
Vicki Cheng, Helen McTaggart-Cowan, Jonathan M. Loree, Rachel A. Murphy, Mikaela Barnes, Haydn Bechthold, Norman Jansen, Mary A. De Vera
Background
With the burden of colorectal cancer in Canada, there is a need to address the psycho-oncologic challenges, including mental health. This study aims to explore the lived mental health experiences in patients with CRC across the phases of the CRC care continuum.
Methods
We employed a patient-oriented constructivist grounded theory design and recruited English speaking participants ≥18 years, diagnosed with CRC within the last 10 years, residing in Canada. We collected data through semi-structured individual interviews using a guide co-constructed with patient research partners. Data collection and analysis were iterative, employed theoretical sampling, and culminated in a theoretical model.
Results
Twenty-eight participants diagnosed with CRC (18 females, 10 males), aged 18–63 years at time of diagnosis were interviewed, with representation across all CRC stages. There were 10 participants (36%) in treatment, 12 participants (43%) in follow-up, and 6 participants (21%) in the beyond phase. We constructed a patient-oriented theory illustrating the dynamic nature between one's self-identity and their mental health experiences across the CRC care continuum. Mental health experiences encompass emotional and cognitive-behavioral responses, expressed differently across phases. Mental health care experiences are also shaped by barriers, facilitators, and individual contextual factors, all of which influence their access to care.
Conclusion
Our theory provides insight into the mental health experiences of patients with CRC across phases of the CRC care continuum. Understanding patients' emotional and cognitive-behavioral responses and care experiences can help identify opportunities to integrate mental health into CRC care.
{"title":"Mental health in people living with and beyond colorectal cancer: A patient-oriented constructivist grounded theory","authors":"Vicki Cheng, Helen McTaggart-Cowan, Jonathan M. Loree, Rachel A. Murphy, Mikaela Barnes, Haydn Bechthold, Norman Jansen, Mary A. De Vera","doi":"10.1002/cam4.70203","DOIUrl":"10.1002/cam4.70203","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With the burden of colorectal cancer in Canada, there is a need to address the psycho-oncologic challenges, including mental health. This study aims to explore the lived mental health experiences in patients with CRC across the phases of the CRC care continuum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed a patient-oriented constructivist grounded theory design and recruited English speaking participants ≥18 years, diagnosed with CRC within the last 10 years, residing in Canada. We collected data through semi-structured individual interviews using a guide co-constructed with patient research partners. Data collection and analysis were iterative, employed theoretical sampling, and culminated in a theoretical model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-eight participants diagnosed with CRC (18 females, 10 males), aged 18–63 years at time of diagnosis were interviewed, with representation across all CRC stages. There were 10 participants (36%) in treatment, 12 participants (43%) in follow-up, and 6 participants (21%) in the beyond phase. We constructed a patient-oriented theory illustrating the dynamic nature between one's self-identity and their mental health experiences across the CRC care continuum. Mental health experiences encompass emotional and cognitive-behavioral responses, expressed differently across phases. Mental health care experiences are also shaped by barriers, facilitators, and individual contextual factors, all of which influence their access to care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our theory provides insight into the mental health experiences of patients with CRC across phases of the CRC care continuum. Understanding patients' emotional and cognitive-behavioral responses and care experiences can help identify opportunities to integrate mental health into CRC care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131357","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}
Yidan Ma, Yifei Wang, Lei He, Jun Du, Lin Li, Zhixin Bie, Yuanming Li, Xiaomao Xu, Wei Zhou, Xiaonan Wu, Li Yang, Jing Di, Chenyang Li, Xiaoguang Li, Dongge Liu, Zheng Wang
Backgroud
Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell-free DNA (cfDNA) in patients with non-small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell-free RNA (cfRNA) is critical for resolving the issue.
Methods
A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi-gene mutations detection by RT-qPCR.
Results
Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4-ALK, ROS1, RET fusions, and MET ex14 skipping.
Conclusion
These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.
{"title":"Preservation of cfRNA in cytological supernatants for cfDNA & cfRNA double detection in non-small cell lung cancer patients","authors":"Yidan Ma, Yifei Wang, Lei He, Jun Du, Lin Li, Zhixin Bie, Yuanming Li, Xiaomao Xu, Wei Zhou, Xiaonan Wu, Li Yang, Jing Di, Chenyang Li, Xiaoguang Li, Dongge Liu, Zheng Wang","doi":"10.1002/cam4.70197","DOIUrl":"10.1002/cam4.70197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgroud</h3>\u0000 \u0000 <p>Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell-free DNA (cfDNA) in patients with non-small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell-free RNA (cfRNA) is critical for resolving the issue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi-gene mutations detection by RT-qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4-ALK, ROS1, RET fusions, and MET ex14 skipping.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131361","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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