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L1CAM is not prognostic factor in HPV-associated adenocarcinoma and adenosquamous cell carcinoma of the uterine cervix.
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.3233/CBM-240101
Jaroslav Klát, Martina Romanová, Vladimír Židlík, Ondřej Šimetka, Adela Kondé

Background: Cervical cancer (CC) is the fourth most common malignancy. The significant prognostic factors are tumor size and lympho-vascular space invasion. Considering that these are nonspecific factors, research has been aimed at finding a specific molecular marker related to a higher incidence of relapse and mortality in patients with CC.

Objective: Our study investigated the prognostic value of L1 cell adhesion molecule (L1CAM) expression in rare histological subtypes of cervical cancer (adenocarcinomas and adenosquamous cell carcinomas).

Methods: This is a single-institution retrospective study with 35 patients who underwent radical hysterectomy for early-stage cervical adenocarcinoma or adenosquamous cell carcinoma in 2007 through 2017. Paraffin sections of the tumor were used for L1CAM analysis by immunohistochemistry.

Results: L1CAM expression was positive in 15 (42.8%) of the 35 tumors. L1CAM expression did not differ significantly in regard to the stage of disease, tumor size, grading, or lymphovascular space invasion (LVSI) (p = 0.619, p = 0.341, p = 0.445, p = 0.999). Progression-free interval and overall survival did not differ between L1CAM-positive and L1CAM-negative groups (p = 0.704, p = 0.386, respectively).

Conclusions: In our study, L1CAM expression is not a negative prognostic factor associated with aggressive tumor behavior, recurrence risk and overall survival.

{"title":"L1CAM is not prognostic factor in HPV-associated adenocarcinoma and adenosquamous cell carcinoma of the uterine cervix.","authors":"Jaroslav Klát, Martina Romanová, Vladimír Židlík, Ondřej Šimetka, Adela Kondé","doi":"10.3233/CBM-240101","DOIUrl":"https://doi.org/10.3233/CBM-240101","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is the fourth most common malignancy. The significant prognostic factors are tumor size and lympho-vascular space invasion. Considering that these are nonspecific factors, research has been aimed at finding a specific molecular marker related to a higher incidence of relapse and mortality in patients with CC.</p><p><strong>Objective: </strong>Our study investigated the prognostic value of L1 cell adhesion molecule (L1CAM) expression in rare histological subtypes of cervical cancer (adenocarcinomas and adenosquamous cell carcinomas).</p><p><strong>Methods: </strong>This is a single-institution retrospective study with 35 patients who underwent radical hysterectomy for early-stage cervical adenocarcinoma or adenosquamous cell carcinoma in 2007 through 2017. Paraffin sections of the tumor were used for L1CAM analysis by immunohistochemistry.</p><p><strong>Results: </strong>L1CAM expression was positive in 15 (42.8%) of the 35 tumors. L1CAM expression did not differ significantly in regard to the stage of disease, tumor size, grading, or lymphovascular space invasion (LVSI) (<i>p</i> = 0.619, <i>p</i> = 0.341, <i>p</i> = 0.445, <i>p</i> = 0.999). Progression-free interval and overall survival did not differ between L1CAM-positive and L1CAM-negative groups (<i>p</i> = 0.704, <i>p</i> = 0.386, respectively).</p><p><strong>Conclusions: </strong>In our study, L1CAM expression is not a negative prognostic factor associated with aggressive tumor behavior, recurrence risk and overall survival.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"41 3","pages":"CBM240101"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumor immune microenvironment of colorectal cancer identifies novel prognostic signature and potential therapeutic drugs.
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.3233/CBM-240110
Weijie Fu, Yunhan Gao, Zhenhai Chen, Song Hu

Background: The tumor microenvironment (TME) is increasingly recognized as a key player in colorectal cancer biology, however, its potential for improving diagnosis, prognosis, and treatment remains unclear. The major aim of this study is to explore the prognostic value of TME related gene in colorectal cancer. Method: Expression matrices and clinical data of colorectal cancer obtained from public databases were divided into TME relevant clusters according to immune characterization. A 11-gene molecular classifier was constructed based on differentially expressed genes between TME clusters and machine learning regression processes. Results: The efficacy and effectiveness of TME based prognostic signature (TPS) were examined in both the training and validation groups. The result indicated that TPS was able to serve as a superior prognosis indicator for colorectal cancer, alone or jointly with other clinical factors. Also, the study demonstrated that high risk colorectal cancer defined by TPS was considered to link with elevated immune infiltration, increased tumor mutation, and worse overall prognosis. Finally, potential therapeutic agents specialized for different risk subgroups of TPS was also identified to improve personalized treatment for colorectal cancer in the future. Conclusions: TPS might be a novel tool to improve the prognosis judgement and personalized treatment of the colorectal cancer in the future.

{"title":"Tumor immune microenvironment of colorectal cancer identifies novel prognostic signature and potential therapeutic drugs.","authors":"Weijie Fu, Yunhan Gao, Zhenhai Chen, Song Hu","doi":"10.3233/CBM-240110","DOIUrl":"https://doi.org/10.3233/CBM-240110","url":null,"abstract":"<p><p><b>Background:</b> The tumor microenvironment (TME) is increasingly recognized as a key player in colorectal cancer biology, however, its potential for improving diagnosis, prognosis, and treatment remains unclear. The major aim of this study is to explore the prognostic value of TME related gene in colorectal cancer. <b>Method:</b> Expression matrices and clinical data of colorectal cancer obtained from public databases were divided into TME relevant clusters according to immune characterization. A 11-gene molecular classifier was constructed based on differentially expressed genes between TME clusters and machine learning regression processes. <b>Results:</b> The efficacy and effectiveness of TME based prognostic signature (TPS) were examined in both the training and validation groups. The result indicated that TPS was able to serve as a superior prognosis indicator for colorectal cancer, alone or jointly with other clinical factors. Also, the study demonstrated that high risk colorectal cancer defined by TPS was considered to link with elevated immune infiltration, increased tumor mutation, and worse overall prognosis. Finally, potential therapeutic agents specialized for different risk subgroups of TPS was also identified to improve personalized treatment for colorectal cancer in the future. <b>Conclusions:</b> TPS might be a novel tool to improve the prognosis judgement and personalized treatment of the colorectal cancer in the future.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"41 3","pages":"CBM240110"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diagnostic utility of lipocalin 2 and metalloproteinase 9 levels in early-stage endometrial cancer.
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.1177/18758592241290951
Songül Ünüvar, Rauf Melekoğlu, Hande Yüce, Nesibe Zeyveli Çelik, Ezgi Bulut Okumuş, Serhat Toprak, Kevser Tanbek, Şeyma Yaşar, Ayşegül Doğan, Neşe Başak Türkmen, Ercan Yılmaz, Süleyman Sandal

Background: Endometrial cancer (EC) is the fourth most common gynecologic malignancy among women. Histopathologic examination is considered gold-standard for diagnosis of EC. However, these examinations sometimes not be useful in distinguishing early stage types of EC.

Objectives: The current study aimed to investigate the clinicopathological significance of Lipocalin-2 (LCN2), matrix metalloproteinase-9 (MMP9), and ferritin in tumor progression.

Methods: A total of 98 patients (55 women newly diagnosed with early-stage endometrial cancer [study group] and 43 women with benign endometrial pathologies [control group]) were enrolled.

Results: There was a significant difference between diagnosis (p < 0.001), surgical procedure (p < 0.001), pathology (p = 0.002), stage (p < 0.001), lymphovascular invasion (LVI) (p = 0.002), myometrial invasion (p < 0.001), and staining intensity (p < 0.001), MMP9 (p = 0.023), LCN2 (p < 0.001), glucocorticoid (GC) (p = 0.048), tumor necrosis factor-alpha (TNF-α) (p = 0.044), menopause duration (p = 0.001), body weight (p < 0.001), and body mass index (BMI) (p < 0.001) were found to be higher, and ferritin levels (p = 0.047) were lower in the endometrial adenocarcinoma group compared to the benign endometrial pathologies.

Conclusion: LCN2, MMP9, and ferritin are practical markers in early cases of endometrial cancer. Serum LCN2 and MMP9 levels may be good clinical tools for the auxiliary diagnosis of early-stage endometrial cancer. Ferritin was also significantly sensitive. Therefore, detecting these markers together may be more beneficial for cancer diagnosis.

{"title":"Diagnostic utility of lipocalin 2 and metalloproteinase 9 levels in early-stage endometrial cancer.","authors":"Songül Ünüvar, Rauf Melekoğlu, Hande Yüce, Nesibe Zeyveli Çelik, Ezgi Bulut Okumuş, Serhat Toprak, Kevser Tanbek, Şeyma Yaşar, Ayşegül Doğan, Neşe Başak Türkmen, Ercan Yılmaz, Süleyman Sandal","doi":"10.1177/18758592241290951","DOIUrl":"https://doi.org/10.1177/18758592241290951","url":null,"abstract":"<p><strong>Background: </strong>Endometrial cancer (EC) is the fourth most common gynecologic malignancy among women. Histopathologic examination is considered gold-standard for diagnosis of EC. However, these examinations sometimes not be useful in distinguishing early stage types of EC.</p><p><strong>Objectives: </strong>The current study aimed to investigate the clinicopathological significance of Lipocalin-2 (LCN2), matrix metalloproteinase-9 (MMP9), and ferritin in tumor progression.</p><p><strong>Methods: </strong>A total of 98 patients (55 women newly diagnosed with early-stage endometrial cancer [study group] and 43 women with benign endometrial pathologies [control group]) were enrolled.</p><p><strong>Results: </strong>There was a significant difference between diagnosis (p < 0.001), surgical procedure (p < 0.001), pathology (p = 0.002), stage (p < 0.001), lymphovascular invasion (LVI) (p = 0.002), myometrial invasion (p < 0.001), and staining intensity (p < 0.001), MMP9 (p = 0.023), LCN2 (p < 0.001), glucocorticoid (GC) (p = 0.048), tumor necrosis factor-alpha (TNF-α) (p = 0.044), menopause duration (p = 0.001), body weight (p < 0.001), and body mass index (BMI) (p < 0.001) were found to be higher, and ferritin levels (p = 0.047) were lower in the endometrial adenocarcinoma group compared to the benign endometrial pathologies.</p><p><strong>Conclusion: </strong>LCN2, MMP9, and ferritin are practical markers in early cases of endometrial cancer. Serum LCN2 and MMP9 levels may be good clinical tools for the auxiliary diagnosis of early-stage endometrial cancer. Ferritin was also significantly sensitive. Therefore, detecting these markers together may be more beneficial for cancer diagnosis.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"41 3","pages":"18758592241290951"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GABPα inhibits tumor progression and angiogenesis via a novel 18-bp indel within VEGF promoter in breast cancer.
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-12-01 DOI: 10.3233/CBM-230541
Hui Guo, Yue Han, Qiaoyi Zhou, Jihua Chen, Mengyi Wang, Xiaotong Deng, Zhenrong Wang, Fan Li, Yao Xu

Background: Pathological angiogenesis is crucial for tumor progression, thus targeting neovascularization is regarded as an effective strategy for cancer therapy. Vascular endothelial growth factor (VEGF), a specific pro-vascular endothelial regulator, contributes to aberrant tumor angiogenesis.

Objective: To identify sequence polymorphisms of VEGF gene and the effects on breast cancer.

Methods: Protein-DNA binding was validated by EMSA and ChIP assay. Gene expression levels were detected by qPCR and western blot. The CCK-8, wound healing and transwell assays were used to assess proliferation, migration, and invasion. Tube formation, CAM, ELISA and IHC assays were performed to evaluate tumor angiogenesis.

Results: A novel 18-bp indel mutation of the VEGF promoter was detected in breast cancer cases, and the deletion allele (DD) presented dominant distribution in patients comparing to the insert type (II). Further analysis revealed that the 18-bp deletion eliminated the recognition sites of GA binding protein alpha (GABPα), which was confirmed by binding experiments. Functionally, the GABPα expression is decreased in breast cancer tissues, and acts as a tumor suppressor to inhibit proliferation, migration, invasion and angiogenesis of breast cancer cells, accompanied by accelerated tumor cell apoptosis. In addition, consistent regulatory roles were investigated in mouse models in response to GABPα overexpression or knockdown as well. Mechanistically, we revealed that GABPα inhibited breast cancer progression and angiogenesis by downregulating VEGF transcription via the 18-bp promoter sequences.

Conclusions: Our findings provide insights into angiogenic targeted strategy aiming at GABPα-VEGF axis in clinical diagnosis and therapy of breast cancer.

{"title":"GABPα inhibits tumor progression and angiogenesis via a novel 18-bp indel within <i>VEGF</i> promoter in breast cancer.","authors":"Hui Guo, Yue Han, Qiaoyi Zhou, Jihua Chen, Mengyi Wang, Xiaotong Deng, Zhenrong Wang, Fan Li, Yao Xu","doi":"10.3233/CBM-230541","DOIUrl":"https://doi.org/10.3233/CBM-230541","url":null,"abstract":"<p><strong>Background: </strong>Pathological angiogenesis is crucial for tumor progression, thus targeting neovascularization is regarded as an effective strategy for cancer therapy. Vascular endothelial growth factor (VEGF), a specific pro-vascular endothelial regulator, contributes to aberrant tumor angiogenesis.</p><p><strong>Objective: </strong>To identify sequence polymorphisms of VEGF gene and the effects on breast cancer.</p><p><strong>Methods: </strong>Protein-DNA binding was validated by EMSA and ChIP assay. Gene expression levels were detected by qPCR and western blot. The CCK-8, wound healing and transwell assays were used to assess proliferation, migration, and invasion. Tube formation, CAM, ELISA and IHC assays were performed to evaluate tumor angiogenesis.</p><p><strong>Results: </strong>A novel 18-bp indel mutation of the VEGF promoter was detected in breast cancer cases, and the deletion allele (DD) presented dominant distribution in patients comparing to the insert type (II). Further analysis revealed that the 18-bp deletion eliminated the recognition sites of GA binding protein alpha (GABPα), which was confirmed by binding experiments. Functionally, the GABPα expression is decreased in breast cancer tissues, and acts as a tumor suppressor to inhibit proliferation, migration, invasion and angiogenesis of breast cancer cells, accompanied by accelerated tumor cell apoptosis. In addition, consistent regulatory roles were investigated in mouse models in response to GABPα overexpression or knockdown as well. Mechanistically, we revealed that GABPα inhibited breast cancer progression and angiogenesis by downregulating VEGF transcription via the 18-bp promoter sequences.</p><p><strong>Conclusions: </strong>Our findings provide insights into angiogenic targeted strategy aiming at GABPα-VEGF axis in clinical diagnosis and therapy of breast cancer.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"41 3","pages":"CBM230541"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanism study of serum extracellular nano-vesicles miR-412-3p targeting regulation of TEAD1 in promoting malignant biological behavior of sub-centimeter lung nodules. 血清细胞外纳米载体 miR-412-3p 靶向调控 TEAD1 促进厘米以下肺结节恶性生物学行为的机制研究
IF 3.1 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-23 DOI: 10.3233/cbm-240137
Yuxia Deng,Nishant Patel,Shuang Ding,Haijun Zhang
OBJECTIVETo investigate the impact and potential mechanisms of serum extracellular nano-vesicles (sEVs) miR-412-3p released from sub-centimeter lung nodules with a diameter of ⩽ 10 mm on the malignant biological function of micro-nodular lung cancer (mnLC).METHODSA total of 87 participants were included and divided into a mnLC group (n= 30), a benign lung nodule (BLN) group (n= 27), and a healthy people control group (n= 30). Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot (WB) were used to measure the morphological characteristics and surface markers of sEVs. In vitro analysis, real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8 cell proliferation assay, clone formation assay, Transwell, stem cell sphere-forming assay, and WB assay were conducted to verify the effect of miR-412-3p/TEAD1 signaling axis on the biological function of lung cancer cells through, respectively. Further validation was conducted using the serum sEVs of the participants.RESULTSThe expression level of sEVs-miR-412-3p in the mnLC group was significantly higher than that in the BLN and healthy groups (P< 0.01). In lung cancer cell lines, miR-412-3p can negatively regulate the targeted gene TEAD1. The miR-412-3p/TEAD1 signaling axis is involved in promoting the EMT signaling pathway and regulating the malignant biological functions of lung cancer cell proliferation, migration, and stemness (P< 0.05). In addition, sEVs in the mnLC group significantly promoted lung cancer cell proliferation, migration, and stemness compared to the BLN and healthy groups, inhibited the expression of E-cadherin and TEAD1 in lung cancer cells, and promoted the expression of N-cadherin and Vimentin (P< 0.05).CONCLUSIONsEVs-miR-412-3p could promote the biological process of EMT, and lead to the occurrence of malignant biological behavior in sub-centimeter lung nodules. This provides evidence for the miR-412-3p/TEAD1 signaling axis as a potential therapeutic target for mnLC.
目的研究直径⩽ 10 mm的亚厘米肺结节释放的血清细胞外纳米载体(sEVs)miR-412-3p对微结节性肺癌(mnLC)恶性生物学功能的影响和潜在机制。方法共纳入 87 名参与者,分为微小结节肺癌组(30 人)、良性肺结节组(27 人)和健康人对照组(30 人)。透射电子显微镜(TEM)、纳米颗粒追踪分析(NTA)和 Western 印迹(WB)用于测量 sEVs 的形态特征和表面标记物。在体外分析中,通过实时定量聚合酶链反应(RT-qPCR)、CCK-8细胞增殖试验、克隆形成试验、Transwell、干细胞球形成试验和WB试验分别验证了miR-412-3p/TEAD1信号轴对肺癌细胞生物学功能的影响。结果mnLC组sEVs-miR-412-3p的表达水平明显高于BLN组和健康组(P< 0.01)。在肺癌细胞系中,miR-412-3p 能负向调节靶基因 TEAD1。miR-412-3p/TEAD1信号轴参与促进EMT信号通路,调控肺癌细胞增殖、迁移和干性等恶性生物学功能(P< 0.05)。此外,与 BLN 组和健康组相比,mnLC 组中的 sEVs 能显著促进肺癌细胞的增殖、迁移和干性,抑制肺癌细胞中 E-cadherin 和 TEAD1 的表达,促进 N-cadherin 和 Vimentin 的表达(P< 0.05)。这为 miR-412-3p/TEAD1 信号轴作为 mnLC 的潜在治疗靶点提供了证据。
{"title":"Mechanism study of serum extracellular nano-vesicles miR-412-3p targeting regulation of TEAD1 in promoting malignant biological behavior of sub-centimeter lung nodules.","authors":"Yuxia Deng,Nishant Patel,Shuang Ding,Haijun Zhang","doi":"10.3233/cbm-240137","DOIUrl":"https://doi.org/10.3233/cbm-240137","url":null,"abstract":"OBJECTIVETo investigate the impact and potential mechanisms of serum extracellular nano-vesicles (sEVs) miR-412-3p released from sub-centimeter lung nodules with a diameter of ⩽ 10 mm on the malignant biological function of micro-nodular lung cancer (mnLC).METHODSA total of 87 participants were included and divided into a mnLC group (n= 30), a benign lung nodule (BLN) group (n= 27), and a healthy people control group (n= 30). Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot (WB) were used to measure the morphological characteristics and surface markers of sEVs. In vitro analysis, real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8 cell proliferation assay, clone formation assay, Transwell, stem cell sphere-forming assay, and WB assay were conducted to verify the effect of miR-412-3p/TEAD1 signaling axis on the biological function of lung cancer cells through, respectively. Further validation was conducted using the serum sEVs of the participants.RESULTSThe expression level of sEVs-miR-412-3p in the mnLC group was significantly higher than that in the BLN and healthy groups (P< 0.01). In lung cancer cell lines, miR-412-3p can negatively regulate the targeted gene TEAD1. The miR-412-3p/TEAD1 signaling axis is involved in promoting the EMT signaling pathway and regulating the malignant biological functions of lung cancer cell proliferation, migration, and stemness (P< 0.05). In addition, sEVs in the mnLC group significantly promoted lung cancer cell proliferation, migration, and stemness compared to the BLN and healthy groups, inhibited the expression of E-cadherin and TEAD1 in lung cancer cells, and promoted the expression of N-cadherin and Vimentin (P< 0.05).CONCLUSIONsEVs-miR-412-3p could promote the biological process of EMT, and lead to the occurrence of malignant biological behavior in sub-centimeter lung nodules. This provides evidence for the miR-412-3p/TEAD1 signaling axis as a potential therapeutic target for mnLC.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"206 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab. 循环肿瘤 DNA (ctDNA) 作为 Nivolumab 治疗晚期肝细胞癌疗效的生物标记物。
IF 3.1 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-21 DOI: 10.3233/cbm-230431
Yehia I Mohamed,Sunyoung S Lee,Tarik Demir,Shadi Chamseddine,Zishuo Ian Hu,Lianchun Xiao,Khaled Elsayes,Jeffrey S Morris,Robert A Wolff,Rikita Hiatia,Aliya Qayyum,Asif Rashid,Dan G Duda,James C Yao,Michael LaPelusa,Eugene J Koay,Armeen Mahvash,Ahmed Al Azzam,Ecaterina E Dumbrava,Manal Hassan,Hesham M Amin,Ahmed Omar Kaseb
BACKGROUNDCirculating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).OBJECTIVEThis study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.METHODSWe analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.RESULTSOf 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04).CONCLUSIONSctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.
背景循环肿瘤DNA(ctDNA)是肝细胞癌(HCC)检测、诊断、治疗选择和预后判断的一种很有前景的非侵入性标记物。目的本研究旨在检验ctDNA作为预后和预测工具在接受尼伐单抗治疗的HCC患者中的实用性。方法我们利用市售平台上的综合基因组检测分析了44名HCC患者治疗前的ctDNA。我们利用对数秩检验和单变量 Cox 模型将总生存期(OS)和无进展生存期(PFS)与 ctDNA 表达相关联。除3名患者外,所有患者都至少发现了一种基因改变,TP53是最常见的改变基因(52.3%)。中位OS为17.5个月(95% CI:12.7,NA)。涉及PIK3CA、BRCA1和CCND1扩增的基因突变与较短的OS相关(P分别为0.0001、0.0001和0.01)。中位生存时间为4.01个月(95% CI:3.06,9.33)。涉及KIT和PIK3CA的突变与较短的PFS相关(P分别为0.0001和0.0004),而涉及CTNNB1的突变与较长的PFS相关(P= 0.04)。需要未来的研究加以证实。
{"title":"Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.","authors":"Yehia I Mohamed,Sunyoung S Lee,Tarik Demir,Shadi Chamseddine,Zishuo Ian Hu,Lianchun Xiao,Khaled Elsayes,Jeffrey S Morris,Robert A Wolff,Rikita Hiatia,Aliya Qayyum,Asif Rashid,Dan G Duda,James C Yao,Michael LaPelusa,Eugene J Koay,Armeen Mahvash,Ahmed Al Azzam,Ecaterina E Dumbrava,Manal Hassan,Hesham M Amin,Ahmed Omar Kaseb","doi":"10.3233/cbm-230431","DOIUrl":"https://doi.org/10.3233/cbm-230431","url":null,"abstract":"BACKGROUNDCirculating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).OBJECTIVEThis study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.METHODSWe analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.RESULTSOf 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04).CONCLUSIONSctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"23 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Machine learning identifies a 5-serum cytokine panel for the early detection of chronic atrophy gastritis patients. 机器学习确定了用于早期检测慢性萎缩性胃炎患者的 5 种血清细胞因子面板。
IF 3.1 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-05 DOI: 10.3233/cbm-240023
Fangmei An,Yan Ge,Wei Ye,Lin Ji,Ke Chen,Yunfei Wang,Xiaoxue Zhang,Shengrong Dong,Yao Shen,Jiamin Zhao,Xiaojuan Gao,Simon Junankar,Robin Barry Chan,Dimitris Christodoulou,Wen Wen,Peihua Lu,Qiang Zhan
BACKGROUNDChronic atrophy gastritis (CAG) is a high-risk pre-cancerous lesion for gastric cancer (GC). The early and accurate detection and discrimination of CAG from benign forms of gastritis (e.g. chronic superficial gastritis, CSG) is critical for optimal management of GC. However, accurate non-invasive methods for the diagnosis of CAG are currently lacking. Cytokines cause inflammation and drive cancer transformation in GC, but their utility as a diagnostic for CAG is poorly characterized.METHODSBlood samples were collected, and 40 cytokines were quantified using a multiplexed immunoassay from 247 patients undergoing screening via endoscopy. Patients were divided into discovery and validation sets. Each cytokine importance was ranked using the feature selection algorithm Boruta. The cytokines with the highest feature importance were selected for machine learning (ML), using the LightGBM algorithm.RESULTSFive serum cytokines (IL-10, TNF-α, Eotaxin, IP-10 and SDF-1a) that could discriminate between CAG and CSG patients were identified and used for predictive model construction. This model was robust and could identify CAG patients with high performance (AUC = 0.88, Accuracy = 0.78). This compared favorably to the conventional approach using the PGI/PGII ratio (AUC = 0.59).CONCLUSIONUsing state-of-the-art ML and a blood-based immunoassay, we developed an improved non-invasive screening method for the detection of precancerous GC lesions.FUNDINGSupported in part by grants from: Jiangsu Science and Technology Project (no. BK20211039); Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2023008); Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021010), Wuxi Science and Technology Bureau Project (no. N20201004); Scientific Research Program of Wuxi Health Commission (Z202208, J202104).
背景:慢性萎缩性胃炎(CAG)是胃癌(GC)的高危癌前病变。早期准确检测 CAG 并将其与良性胃炎(如慢性浅表性胃炎,CSG)区分开来对于胃癌的最佳治疗至关重要。然而,目前尚缺乏诊断 CAG 的准确非侵入性方法。方法收集 247 名接受内镜筛查的患者的血样,并使用多重免疫测定法量化 40 种细胞因子。患者被分为发现组和验证组。使用特征选择算法 Boruta 对每种细胞因子的重要性进行排序。结果确定了能区分 CAG 和 CSG 患者的五种血清细胞因子(IL-10、TNF-α、Eotaxin、IP-10 和 SDF-1a),并将其用于构建预测模型。该模型非常稳健,能高效识别 CAG 患者(AUC = 0.88,准确率 = 0.78)。结论利用最先进的 ML 和血液免疫测定技术,我们开发出了一种用于检测 GC 癌前病变的改进型无创筛查方法。BK20211039);无锡市卫生委员会中青年拔尖人才支持计划(BJ2023008);无锡市卫生委员会医学重点学科计划(ZDXK2021010),无锡市科技局项目(编号:N20201004);无锡市卫生委员会科研计划(Z202208,J202104)。
{"title":"Machine learning identifies a 5-serum cytokine panel for the early detection of chronic atrophy gastritis patients.","authors":"Fangmei An,Yan Ge,Wei Ye,Lin Ji,Ke Chen,Yunfei Wang,Xiaoxue Zhang,Shengrong Dong,Yao Shen,Jiamin Zhao,Xiaojuan Gao,Simon Junankar,Robin Barry Chan,Dimitris Christodoulou,Wen Wen,Peihua Lu,Qiang Zhan","doi":"10.3233/cbm-240023","DOIUrl":"https://doi.org/10.3233/cbm-240023","url":null,"abstract":"BACKGROUNDChronic atrophy gastritis (CAG) is a high-risk pre-cancerous lesion for gastric cancer (GC). The early and accurate detection and discrimination of CAG from benign forms of gastritis (e.g. chronic superficial gastritis, CSG) is critical for optimal management of GC. However, accurate non-invasive methods for the diagnosis of CAG are currently lacking. Cytokines cause inflammation and drive cancer transformation in GC, but their utility as a diagnostic for CAG is poorly characterized.METHODSBlood samples were collected, and 40 cytokines were quantified using a multiplexed immunoassay from 247 patients undergoing screening via endoscopy. Patients were divided into discovery and validation sets. Each cytokine importance was ranked using the feature selection algorithm Boruta. The cytokines with the highest feature importance were selected for machine learning (ML), using the LightGBM algorithm.RESULTSFive serum cytokines (IL-10, TNF-α, Eotaxin, IP-10 and SDF-1a) that could discriminate between CAG and CSG patients were identified and used for predictive model construction. This model was robust and could identify CAG patients with high performance (AUC = 0.88, Accuracy = 0.78). This compared favorably to the conventional approach using the PGI/PGII ratio (AUC = 0.59).CONCLUSIONUsing state-of-the-art ML and a blood-based immunoassay, we developed an improved non-invasive screening method for the detection of precancerous GC lesions.FUNDINGSupported in part by grants from: Jiangsu Science and Technology Project (no. BK20211039); Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2023008); Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021010), Wuxi Science and Technology Bureau Project (no. N20201004); Scientific Research Program of Wuxi Health Commission (Z202208, J202104).","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of RNA-binding protein RBMS3 as a potential biomarker for immunotherapy in bladder cancer. 将 RNA 结合蛋白 RBMS3 鉴定为膀胱癌免疫疗法的潜在生物标记物。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-04 DOI: 10.3233/CBM-230489
Tarimo Fredrick Praygod, Jinlong Li, Hongwei Li, Wanlong Tan, Zhiming Hu, Li Zhou

RNA-binding protein (RBP) plays pivotal roles in the malignant progression of cancer by regulating gene expression. In this paper, we aimed to develop RBP-based prognostic signature and identify critical hub RBPs in bladder cancer (BLCA). Firstly, a risk model based on differentially expressed RBP gens (DERBPs) between normal and tumor tissues was successfully established, which can predict the tumor stromal score and drug sensitivity. Then two another RBP risk models based on miRNA-correlated RBPs or lncRNA-correlated RBPs were also established, and RBMS3 was identified as the overlapping gene in the three models. Data from multiple bioinformatics databases revealed that RBMS3 was an independent prognostic factor for overall survival (OS), and was associated with an immunosuppressive tumor microenvironment (TME) in BLCA. Further, Single-cell RNA-Seq (scRNA-Seq) data and the human protein altas (HPA) database showed that RBMS3 expression (both mRNA and protein) were up-regulated in BLCA tumor and tumor stromal cells. Finally, RBMS3 was shown to be associated with worse response to BLCA immunotherapy. Overall, RBMS3 is a key prognostic RBP with TME remodeling function and may serve as a target for BLCA immunotherapy.

RNA 结合蛋白(RBP)通过调控基因表达在癌症的恶性进展中发挥着关键作用。本文旨在建立基于 RBP 的预后特征,并识别膀胱癌(BLCA)中的关键枢纽 RBP。首先,我们成功建立了一个基于正常组织和肿瘤组织间差异表达 RBP 基因(DERBPs)的风险模型,该模型可预测肿瘤基质评分和药物敏感性。此外,还建立了另外两个基于miRNA相关RBPs或lncRNA相关RBPs的RBP风险模型,并发现RBMS3是这三个模型中的重叠基因。来自多个生物信息学数据库的数据显示,RBMS3是影响总生存期(OS)的独立预后因素,并与BLCA的免疫抑制性肿瘤微环境(TME)相关。此外,单细胞RNA-Seq(scRNA-Seq)数据和人类蛋白质数据库(HPA)显示,RBMS3的表达(mRNA和蛋白质)在BLCA肿瘤和肿瘤基质细胞中上调。最后,RBMS3 与 BLCA 免疫疗法的不良反应有关。总之,RBMS3是一种关键的预后RBP,具有TME重塑功能,可作为BLCA免疫疗法的靶点。
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引用次数: 0
A computed tomography-based score indicative of lung cancer aggression (SILA) predicts lung adenocarcinomas with low malignant potential or vascular invasion. 基于计算机断层扫描的肺癌侵袭性评分(SILA)可预测恶性程度低或有血管侵犯的肺腺癌。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-05-22 DOI: 10.3233/CBM-230456
Dylan Steiner, Ju Ae Park, Sarah Singh, Austin Potter, Jonathan Scalera, Jennifer Beane, Kei Suzuki, Marc E Lenburg, Eric J Burks

Background: Histologic grading of lung adenocarcinoma (LUAD) is predictive of outcome but is only possible after surgical resection. A radiomic biomarker predictive of grade has the potential to improve preoperative management of early-stage LUAD.

Objective: Validate a prognostic radiomic score indicative of lung cancer aggression (SILA) in surgically resected stage I LUAD (n= 161) histologically graded as indolent low malignant potential (LMP), intermediate, or aggressive vascular invasive (VI) subtypes.

Methods: The SILA scores were generated from preoperative CT-scans using the previously validated Computer-Aided Nodule Assessment and Risk Yield (CANARY) software.

Results: Cox proportional regression showed significant association between the SILA and 7-year recurrence-free survival (RFS) in a univariate (p< 0.05) and multivariate (p< 0.05) model incorporating age, gender, smoking status, pack years, and extent of resection. The SILA was positively correlated with invasive size (spearman r= 0.54, p= 8.0 × 10 - 14) and negatively correlated with percentage of lepidic histology (spearman r=-0.46, p= 7.1 × 10 - 10). The SILA predicted indolent LMP with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.74 and aggressive VI with an AUC of 0.71, the latter remaining significant when invasive size was included as a covariate in a logistic regression model (p< 0.01).

Conclusions: The SILA scoring of preoperative CT scans was prognostic and predictive of resected pathologic grade.

背景:肺腺癌(LUAD)的组织学分级可预测预后,但只有在手术切除后才能进行分级。预测分级的放射生物标志物有望改善早期肺腺癌的术前管理:目的:在手术切除的 I 期 LUAD(161 例)患者中验证肺癌侵袭性放射学评分(SILA),该评分在组织学上被分级为轻度低恶性潜能亚型(LMP)、中度亚型或侵袭性血管浸润亚型(VI):SILA评分由术前CT扫描结果生成,使用的是之前经过验证的计算机辅助结节评估和风险收益(CANARY)软件:结果:Cox比例回归显示,在单变量(p< 0.05)和多变量(p< 0.05)模型中,SILA与7年无复发生存率(RFS)之间存在显著关联,多变量模型包括年龄、性别、吸烟状况、包年和切除范围。SILA与浸润性大小呈正相关(spearman r=0.54,p= 8.0 × 10 - 14),与鳞状组织学百分比呈负相关(spearman r=-0.46,p= 7.1 × 10 - 10)。SILA预测惰性LMP的接收者操作特征曲线(ROC)下面积(AUC)为0.74,预测侵袭性VI的接收者操作特征曲线(ROC)下面积(AUC)为0.71,当在逻辑回归模型中将侵袭性大小作为协变量时,后者仍然显著(p< 0.01):结论:术前CT扫描的SILA评分可预测预后并预示切除的病理分级。
{"title":"A computed tomography-based score indicative of lung cancer aggression (SILA) predicts lung adenocarcinomas with low malignant potential or vascular invasion.","authors":"Dylan Steiner, Ju Ae Park, Sarah Singh, Austin Potter, Jonathan Scalera, Jennifer Beane, Kei Suzuki, Marc E Lenburg, Eric J Burks","doi":"10.3233/CBM-230456","DOIUrl":"https://doi.org/10.3233/CBM-230456","url":null,"abstract":"<p><strong>Background: </strong>Histologic grading of lung adenocarcinoma (LUAD) is predictive of outcome but is only possible after surgical resection. A radiomic biomarker predictive of grade has the potential to improve preoperative management of early-stage LUAD.</p><p><strong>Objective: </strong>Validate a prognostic radiomic score indicative of lung cancer aggression (SILA) in surgically resected stage I LUAD (n= 161) histologically graded as indolent low malignant potential (LMP), intermediate, or aggressive vascular invasive (VI) subtypes.</p><p><strong>Methods: </strong>The SILA scores were generated from preoperative CT-scans using the previously validated Computer-Aided Nodule Assessment and Risk Yield (CANARY) software.</p><p><strong>Results: </strong>Cox proportional regression showed significant association between the SILA and 7-year recurrence-free survival (RFS) in a univariate (p< 0.05) and multivariate (p< 0.05) model incorporating age, gender, smoking status, pack years, and extent of resection. The SILA was positively correlated with invasive size (spearman r= 0.54, p= 8.0 × 10 - 14) and negatively correlated with percentage of lepidic histology (spearman r=-0.46, p= 7.1 × 10 - 10). The SILA predicted indolent LMP with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.74 and aggressive VI with an AUC of 0.71, the latter remaining significant when invasive size was included as a covariate in a logistic regression model (p< 0.01).</p><p><strong>Conclusions: </strong>The SILA scoring of preoperative CT scans was prognostic and predictive of resected pathologic grade.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LDCT image biomarkers that matter most for the deep learning classification of indeterminate pulmonary nodules. 对不确定肺结节深度学习分类最重要的 LDCT 图像生物标志物。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-05-22 DOI: 10.3233/CBM-230444
Axel H Masquelin, Nick Cheney, Raúl San José Estépar, Jason H T Bates, C Matthew Kinsey

Background: Continued improvement in deep learning methodologies has increased the rate at which deep neural networks are being evaluated for medical applications, including diagnosis of lung cancer. However, there has been limited exploration of the underlying radiological characteristics that the network relies on to identify lung cancer in computed tomography (CT) images.

Objective: In this study, we used a combination of image masking and saliency activation maps to systematically explore the contributions of both parenchymal and tumor regions in a CT image to the classification of indeterminate lung nodules.

Methods: We selected individuals from the National Lung Screening Trial (NLST) with solid pulmonary nodules 4-20 mm in diameter. Segmentation masks were used to generate three distinct datasets; 1) an Original Dataset containing the complete low-dose CT scans from the NLST, 2) a Parenchyma-Only Dataset in which the tumor regions were covered by a mask, and 3) a Tumor-Only Dataset in which only the tumor regions were included.

Results: The Original Dataset significantly outperformed the Parenchyma-Only Dataset and the Tumor-Only Dataset with an AUC of 80.80 ± 3.77% compared to 76.39 ± 3.16% and 78.11 ± 4.32%, respectively. Gradient-weighted class activation mapping (Grad-CAM) of the Original Dataset showed increased attention was being given to the nodule and the tumor-parenchyma boundary when nodules were classified as malignant. This pattern of attention remained unchanged in the case of the Parenchyma-Only Dataset. Nodule size and first-order statistical features of the nodules were significantly different with the average malignant and benign nodule maximum 3d diameter being 23 mm and 12 mm, respectively.

Conclusion: We conclude that network performance is linked to textural features of nodules such as kurtosis, entropy and intensity, as well as morphological features such as sphericity and diameter. Furthermore, textural features are more positively associated with malignancy than morphological features.

背景:深度学习方法的不断改进提高了深度神经网络在医疗应用(包括肺癌诊断)方面的评估速度。然而,人们对网络在计算机断层扫描(CT)图像中识别肺癌所依赖的基本放射学特征的探索还很有限:在这项研究中,我们结合使用了图像遮蔽和显著性激活图,系统地探索了 CT 图像中实质和肿瘤区域对不确定肺结节分类的贡献:我们从国家肺部筛查试验(NLST)中选取了直径为 4-20 毫米的实性肺结节患者。使用分割掩膜生成三个不同的数据集:1)原始数据集,包含 NLST 的完整低剂量 CT 扫描图像;2)仅包含实质组织的数据集,其中肿瘤区域被掩膜覆盖;3)仅包含肿瘤的数据集,其中只包含肿瘤区域:结果:原始数据集的 AUC 为 80.80 ± 3.77%,明显优于仅包含实质组织的数据集和仅包含肿瘤的数据集,而原始数据集和原始数据集的 AUC 分别为 76.39 ± 3.16% 和 78.11 ± 4.32%。原始数据集的梯度加权类激活图谱(Grad-CAM)显示,当结节被归类为恶性时,结节和肿瘤-实质边界会受到更多关注。在仅实质数据集的情况下,这种关注模式保持不变。结节的大小和一阶统计特征存在显著差异,恶性和良性结节的平均最大 3d 直径分别为 23 毫米和 12 毫米:我们得出结论,网络性能与结节的纹理特征(如峰度、熵和强度)以及形态特征(如球形度和直径)有关。此外,与形态特征相比,纹理特征与恶性程度的正相关性更高。
{"title":"LDCT image biomarkers that matter most for the deep learning classification of indeterminate pulmonary nodules.","authors":"Axel H Masquelin, Nick Cheney, Raúl San José Estépar, Jason H T Bates, C Matthew Kinsey","doi":"10.3233/CBM-230444","DOIUrl":"10.3233/CBM-230444","url":null,"abstract":"<p><strong>Background: </strong>Continued improvement in deep learning methodologies has increased the rate at which deep neural networks are being evaluated for medical applications, including diagnosis of lung cancer. However, there has been limited exploration of the underlying radiological characteristics that the network relies on to identify lung cancer in computed tomography (CT) images.</p><p><strong>Objective: </strong>In this study, we used a combination of image masking and saliency activation maps to systematically explore the contributions of both parenchymal and tumor regions in a CT image to the classification of indeterminate lung nodules.</p><p><strong>Methods: </strong>We selected individuals from the National Lung Screening Trial (NLST) with solid pulmonary nodules 4-20 mm in diameter. Segmentation masks were used to generate three distinct datasets; 1) an Original Dataset containing the complete low-dose CT scans from the NLST, 2) a Parenchyma-Only Dataset in which the tumor regions were covered by a mask, and 3) a Tumor-Only Dataset in which only the tumor regions were included.</p><p><strong>Results: </strong>The Original Dataset significantly outperformed the Parenchyma-Only Dataset and the Tumor-Only Dataset with an AUC of 80.80 ± 3.77% compared to 76.39 ± 3.16% and 78.11 ± 4.32%, respectively. Gradient-weighted class activation mapping (Grad-CAM) of the Original Dataset showed increased attention was being given to the nodule and the tumor-parenchyma boundary when nodules were classified as malignant. This pattern of attention remained unchanged in the case of the Parenchyma-Only Dataset. Nodule size and first-order statistical features of the nodules were significantly different with the average malignant and benign nodule maximum 3d diameter being 23 mm and 12 mm, respectively.</p><p><strong>Conclusion: </strong>We conclude that network performance is linked to textural features of nodules such as kurtosis, entropy and intensity, as well as morphological features such as sphericity and diameter. Furthermore, textural features are more positively associated with malignancy than morphological features.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141289004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Cancer Biomarkers
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