Introduction: There is a need for a rapid, accurate, less-invasive approach to distinguishing malignant from benign pleural effusions. We investigated the diagnostic value of five pleural tumor markers in exudative pleural effusions.
Methods: By immunochemiluminescence assay, we measured pleural concentrations of tumor markers. We used the receiver operating characteristic curve analysis to assess their diagnostic values.
Results: A total of 281 patients were enrolled. All tumor markers were significantly higher in malignant pleural effusions than benign ones. The area under the curve of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 15-3, cytokeratin fragment 19 (CYFRA) 21-1, CA-19-9, and CA-125 were 0.81, 0.78, 0.75, 0.65, and 0.65, respectively. Combined markers of CEA + CA-15-3 and CEA + CA-15-3 + CYFRA 21-1 had a sensitivity of 87% and 94%, and specificity of 75% and 58%, respectively. We designed a diagnostic algorithm by combining pleural cytology with pleural tumor marker assay. CEA + CYFRA 21-1 + CA-19-9 + CA-15-3 was the best tumor markers panel detecting 96% of cytologically negative malignant pleural effusions, with a negative predictive value of 98%.
Conclusions: Although cytology is specific enough, it has less sensitivity in identifying malignant pleural fluids. As a result, the main gap is detecting malignant pleural effusions with negative cytology. CEA was the best single marker, followed by CA-15-3 and CYFRA 21-1. Through both cytology and suggested panels of tumor markers, malignant and benign pleural effusions could be truly diagnosed with an accuracy of about 98% without the need for more invasive procedures, except for the cohort with negative cytology and a positive tumor markers panel, which require more investigations.
{"title":"Pleural CEA, CA-15-3, CYFRA 21-1, CA-19-9, CA-125 discriminating malignant from benign pleural effusions: Diagnostic cancer biomarkers.","authors":"Farzaneh Fazli Khalaf, Mehrnaz Asadi Gharabaghi, Maryam Balibegloo, Hamidreza Davari, Samaneh Afshar, Behnaz Jahanbin","doi":"10.1177/03936155231158661","DOIUrl":"https://doi.org/10.1177/03936155231158661","url":null,"abstract":"<p><strong>Introduction: </strong>There is a need for a rapid, accurate, less-invasive approach to distinguishing malignant from benign pleural effusions. We investigated the diagnostic value of five pleural tumor markers in exudative pleural effusions.</p><p><strong>Methods: </strong>By immunochemiluminescence assay, we measured pleural concentrations of tumor markers. We used the receiver operating characteristic curve analysis to assess their diagnostic values.</p><p><strong>Results: </strong>A total of 281 patients were enrolled. All tumor markers were significantly higher in malignant pleural effusions than benign ones. The area under the curve of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 15-3, cytokeratin fragment 19 (CYFRA) 21-1, CA-19-9, and CA-125 were 0.81, 0.78, 0.75, 0.65, and 0.65, respectively. Combined markers of CEA + CA-15-3 and CEA + CA-15-3 + CYFRA 21-1 had a sensitivity of 87% and 94%, and specificity of 75% and 58%, respectively. We designed a diagnostic algorithm by combining pleural cytology with pleural tumor marker assay. CEA + CYFRA 21-1 + CA-19-9 + CA-15-3 was the best tumor markers panel detecting 96% of cytologically negative malignant pleural effusions, with a negative predictive value of 98%.</p><p><strong>Conclusions: </strong>Although cytology is specific enough, it has less sensitivity in identifying malignant pleural fluids. As a result, the main gap is detecting malignant pleural effusions with negative cytology. CEA was the best single marker, followed by CA-15-3 and CYFRA 21-1. Through both cytology and suggested panels of tumor markers, malignant and benign pleural effusions could be truly diagnosed with an accuracy of about 98% without the need for more invasive procedures, except for the cohort with negative cytology and a positive tumor markers panel, which require more investigations.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9674625","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}
Pub Date : 2023-06-01DOI: 10.1177/03936155231163599
Ningfeng Li, Yan Zhang, Wenjie Qu, Chao Zhang, Zhaoxia Ding, Linlin Wang, Baoxia Cui
Objective: Peripheral systemic inflammatory, nutritional, and coagulation biomarkers have prognostic and predictive value in various malignancies. We evaluated the prognostic and predictive roles of systemic inflammatory, nutritional, and coagulation biomarkers in the circulating blood of patients with advanced cervical cancer.
Methods: A retrospective study of 795 patients with cervical cancer who received concurrent chemoradiation therapy was performed. Overall survival was evaluated by the Kaplan-Meier estimator. Univariate and multivariate Cox regression models were used to determine prognostic factors associated with overall survival.
Results: The median follow-up time was 76 months. In the univariate analysis, overall survival showed positive prognostic value in patients with a platelet-to-lymphocyte ratio (PLR) <164.29 (P = 0.010), and a plasma fibrinogen (FIB) level <4 g/L(P = 0.012). In the multivariate analysis, the PLR (P = 0.036), and FIB level (P = 0.047) maintained their significance for overall survival. Therefore, the PLR and FIB levels are independent prognostic factors in patients with advanced cervical cancer.
Conclusions: Systemic inflammatory and coagulation biomarkers could help to understand survival differences in the clinical treatment of advanced cervical cancer. The PLR and FIB levels are independent prognostic factors of poor survival in patients with advanced cervical cancer.
{"title":"Analysis of systemic inflammatory and coagulation biomarkers in advanced cervical cancer: Prognostic and predictive significance.","authors":"Ningfeng Li, Yan Zhang, Wenjie Qu, Chao Zhang, Zhaoxia Ding, Linlin Wang, Baoxia Cui","doi":"10.1177/03936155231163599","DOIUrl":"https://doi.org/10.1177/03936155231163599","url":null,"abstract":"<p><strong>Objective: </strong>Peripheral systemic inflammatory, nutritional, and coagulation biomarkers have prognostic and predictive value in various malignancies. We evaluated the prognostic and predictive roles of systemic inflammatory, nutritional, and coagulation biomarkers in the circulating blood of patients with advanced cervical cancer.</p><p><strong>Methods: </strong>A retrospective study of 795 patients with cervical cancer who received concurrent chemoradiation therapy was performed. Overall survival was evaluated by the Kaplan-Meier estimator. Univariate and multivariate Cox regression models were used to determine prognostic factors associated with overall survival.</p><p><strong>Results: </strong>The median follow-up time was 76 months. In the univariate analysis, overall survival showed positive prognostic value in patients with a platelet-to-lymphocyte ratio (PLR) <164.29 (<i>P</i> = 0.010), and a plasma fibrinogen (FIB) level <4 g/L(<i>P</i> = 0.012). In the multivariate analysis, the PLR (<i>P</i> = 0.036), and FIB level (<i>P</i> = 0.047) maintained their significance for overall survival. Therefore, the PLR and FIB levels are independent prognostic factors in patients with advanced cervical cancer.</p><p><strong>Conclusions: </strong>Systemic inflammatory and coagulation biomarkers could help to understand survival differences in the clinical treatment of advanced cervical cancer. The PLR and FIB levels are independent prognostic factors of poor survival in patients with advanced cervical cancer.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9724590","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}
Background: The DNA mismatch repair system is one of the defense mechanisms in the body, and the inactivation of mismatch repair plays a pivotal role in secondary carcinogenesis and progression. However, the significance of mismatch repair in esophageal squamous cell carcinoma (ESCC) has not been established. In this study, we explored the diagnostic and prognostic significance of mismatch repair markers, mutL homologue 1 (MLH1), post-meiotic segregation increased 2 (PMS2), mutS homologue 2 (MSH2), and mutS homologue 6 (MSH6), in patients with ESCC.
Methods: We used a notation based on the proportion of immunoreactivity/expression for immunohistochemistry (PRIME notation), which allows the comparison of mismatch repair expression by assigning a score to PRIME notation. MLH1, PMS2, MSH2, and MSH6 were examined immunohistochemically in 189 surgically resected ESCC specimens.
Results: A total of 100/189 patients with ESCC (53%) received preoperative chemotherapy. The rates of ESCC cases with decreased mismatch repair status were 13.2%, 15.3%, 24.8%, and 12.6% for MLH1, PMS2, MSH2, and MSH6, respectively. The decreased status of individual mismatch repair markers was significantly correlated with worse prognosis in patients with ESCC. Additionally, MSH2, MSH6, and PMS2 were significantly associated with response to preoperative chemotherapy. Multivariate analysis revealed that MLH1, PMS2, and MSH2 are independent prognostic factors.
Conclusion: Our results suggest that mismatch repair is a prognostic biomarker for ESCC and could contribute to the selection of appropriate adjuvant therapy for patients with ESCC.
{"title":"MMR markers correlate with clinical outcome in patients with esophageal squamous cell carcinoma.","authors":"Takuro Yamauchi, Fumiyoshi Fujishima, Junichi Tsunokake, Atsushi Kunimitsu, Ryujiro Akaishi, Yohei Ozawa, Toshiaki Fukutomi, Hiroshi Okamoto, Chiaki Sato, Yusuke Taniyama, Takashi Kamei, Ryo Ichinohasama, Hironobu Sasano","doi":"10.1177/03936155231165068","DOIUrl":"https://doi.org/10.1177/03936155231165068","url":null,"abstract":"<p><strong>Background: </strong>The DNA mismatch repair system is one of the defense mechanisms in the body, and the inactivation of mismatch repair plays a pivotal role in secondary carcinogenesis and progression. However, the significance of mismatch repair in esophageal squamous cell carcinoma (ESCC) has not been established. In this study, we explored the diagnostic and prognostic significance of mismatch repair markers, mutL homologue 1 (MLH1), post-meiotic segregation increased 2 (PMS2), mutS homologue 2 (MSH2), and mutS homologue 6 (MSH6), in patients with ESCC.</p><p><strong>Methods: </strong>We used a notation based on the proportion of immunoreactivity/expression for immunohistochemistry (PRIME notation), which allows the comparison of mismatch repair expression by assigning a score to PRIME notation. MLH1, PMS2, MSH2, and MSH6 were examined immunohistochemically in 189 surgically resected ESCC specimens.</p><p><strong>Results: </strong>A total of 100/189 patients with ESCC (53%) received preoperative chemotherapy. The rates of ESCC cases with decreased mismatch repair status were 13.2%, 15.3%, 24.8%, and 12.6% for MLH1, PMS2, MSH2, and MSH6, respectively. The decreased status of individual mismatch repair markers was significantly correlated with worse prognosis in patients with ESCC. Additionally, MSH2, MSH6, and PMS2 were significantly associated with response to preoperative chemotherapy. Multivariate analysis revealed that MLH1, PMS2, and MSH2 are independent prognostic factors.</p><p><strong>Conclusion: </strong>Our results suggest that mismatch repair is a prognostic biomarker for ESCC and could contribute to the selection of appropriate adjuvant therapy for patients with ESCC.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044476","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}
Background: Dysbiosis commonly occurs in pancreatic cancer, but its specific characteristics and interactions with pancreatic cancer remain obscure.
Materials and methods: The 16S rRNA sequencing method was used to analyze multisite (oral and gut) microbiota characteristics of pancreatic cancer, chronic pancreatitis, and healthy controls. Differential analysis was used to identify the pancreatic cancer-associated genera and pathways. A random forest algorithm was adopted to establish the diagnostic models for pancreatic cancer.
Results: The chronic pancreatitis group exhibited the lowest microbial diversity, while no significant difference was found between the pancreatic cancer group and healthy controls group. Diagnostic models based on the characteristics of the oral (area under the curve (AUC) 0.916, 95% confidence interval (CI) 0.832-1) or gut (AUC 0.856; 95% CI 0.74, 0.972) microbiota effectively discriminate the pancreatic cancer samples in this study, suggesting saliva as a superior sample type in terms of detection efficiency and clinical compliance. Oral pathogenic genera (Granulicatella, Peptostreptococcus, Alloprevotella, Veillonella, etc.) and gut opportunistic genera (Prevotella, Bifidobacterium, Escherichia/Shigella, Peptostreptococcus, Actinomyces, etc.), were significantly enriched in pancreatic cancer. The 16S function prediction analysis revealed that inflammation, immune suppression, and barrier damage pathways were involved in the course of pancreatic cancer.
Conclusion: This study comprehensively described the microbiota characteristics of pancreatic cancer and suggested potential microbial markers as non-invasive tools for pancreatic cancer diagnosis.
背景:胰腺癌患者通常会出现菌群失调,但其具体特征及其与胰腺癌的相互作用仍不明确:采用 16S rRNA 测序方法分析胰腺癌、慢性胰腺炎和健康对照组的多位点(口腔和肠道)微生物群特征。差异分析用于确定胰腺癌相关菌属和通路。采用随机森林算法建立了胰腺癌诊断模型:结果:慢性胰腺炎组的微生物多样性最低,而胰腺癌组与健康对照组之间无明显差异。在这项研究中,基于口腔(曲线下面积(AUC)0.916,95% 置信区间(CI)0.832-1)或肠道(AUC 0.856;95% CI 0.74,0.972)微生物群特征的诊断模型能有效区分胰腺癌样本,这表明唾液在检测效率和临床依从性方面是一种更优越的样本类型。口腔致病菌属(粒细胞菌属、肽链球菌属、全链球菌属、维龙菌属等)和肠道机会性菌属(普雷沃菌属、双歧杆菌属、埃希菌属/志贺菌属、肽链球菌属、放线菌属等)在胰腺癌中显著富集。16S 功能预测分析表明,炎症、免疫抑制和屏障损伤途径参与了胰腺癌的发病过程:这项研究全面描述了胰腺癌微生物群的特征,并提出了潜在的微生物标记物作为胰腺癌诊断的非侵入性工具。
{"title":"Alterations of commensal microbiota are associated with pancreatic cancer.","authors":"Tian Chen, Xuejiao Li, Gaoming Li, Yun Liu, Xiaochun Huang, Wei Ma, Chao Qian, Jie Guo, Shuo Wang, Qin Qin, Shanrong Liu","doi":"10.1177/03936155231166721","DOIUrl":"10.1177/03936155231166721","url":null,"abstract":"<p><strong>Background: </strong>Dysbiosis commonly occurs in pancreatic cancer, but its specific characteristics and interactions with pancreatic cancer remain obscure.</p><p><strong>Materials and methods: </strong>The 16S rRNA sequencing method was used to analyze multisite (oral and gut) microbiota characteristics of pancreatic cancer, chronic pancreatitis, and healthy controls. Differential analysis was used to identify the pancreatic cancer-associated genera and pathways. A random forest algorithm was adopted to establish the diagnostic models for pancreatic cancer.</p><p><strong>Results: </strong>The chronic pancreatitis group exhibited the lowest microbial diversity, while no significant difference was found between the pancreatic cancer group and healthy controls group. Diagnostic models based on the characteristics of the oral (area under the curve (AUC) 0.916, 95% confidence interval (CI) 0.832-1) or gut (AUC 0.856; 95% CI 0.74, 0.972) microbiota effectively discriminate the pancreatic cancer samples in this study, suggesting saliva as a superior sample type in terms of detection efficiency and clinical compliance. Oral pathogenic genera (<i>Granulicatella</i>, <i>Peptostreptococcus</i>, <i>Alloprevotella</i>, <i>Veillonella</i>, etc.) and gut opportunistic genera (<i>Prevotella</i>, <i>Bifidobacterium</i>, <i>Escherichia/Shigella</i>, <i>Peptostreptococcus</i>, <i>Actinomyces</i>, etc.), were significantly enriched in pancreatic cancer. The 16S function prediction analysis revealed that inflammation, immune suppression, and barrier damage pathways were involved in the course of pancreatic cancer.</p><p><strong>Conclusion: </strong>This study comprehensively described the microbiota characteristics of pancreatic cancer and suggested potential microbial markers as non-invasive tools for pancreatic cancer diagnosis.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9674648","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}
Background: To evaluate the diagnostic value of combinations of tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA153, and CA19-9 in identifying malignant pleural effusion (MPE) from non-malignant pleural effusion (non-MPE) using machine learning, and compare the performance of popular machine learning methods.
Methods: A total of 319 samples were collected from patients with pleural effusion in Beijing and Wuhan, China, from January 2018 to June 2020. Five machine learning methods including Logistic regression, extreme gradient boosting (XGBoost), Bayesian additive regression tree, random forest, and support vector machine were applied to evaluate the diagnostic performance. Sensitivity, specificity, Youden's index, and the area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of different diagnostic models.
Results: For diagnostic models with a single tumor marker, the model using CEA, constructed by XGBoost, performed best (AUC = 0.895, sensitivity = 0.80), and the model with CA153, also by XGBoost, showed the largest specificity 0.98. Among all combinations of tumor markers, the combination of CEA and CA153 achieved the best performance (AUC = 0.921, sensitivity = 0.85) in identifying MPE under the diagnostic model constructed by XGBoost.
Conclusions: Diagnostic models for MPE with a combination of multiple tumor markers outperformed the models with a single tumor marker, particularly in sensitivity. Using machine learning methods, especially XGBoost, could comprehensively improve the diagnostic accuracy of MPE.
{"title":"Diagnosis of malignant pleural effusion with combinations of multiple tumor markers: A comparison study of five machine learning models.","authors":"Yixi Zhang, Jingyuan Wang, Baosheng Liang, Hanyu Wu, Yangyu Chen","doi":"10.1177/03936155231158125","DOIUrl":"https://doi.org/10.1177/03936155231158125","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the diagnostic value of combinations of tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA153, and CA19-9 in identifying malignant pleural effusion (MPE) from non-malignant pleural effusion (non-MPE) using machine learning, and compare the performance of popular machine learning methods.</p><p><strong>Methods: </strong>A total of 319 samples were collected from patients with pleural effusion in Beijing and Wuhan, China, from January 2018 to June 2020. Five machine learning methods including Logistic regression, extreme gradient boosting (XGBoost), Bayesian additive regression tree, random forest, and support vector machine were applied to evaluate the diagnostic performance. Sensitivity, specificity, Youden's index, and the area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of different diagnostic models.</p><p><strong>Results: </strong>For diagnostic models with a single tumor marker, the model using CEA, constructed by XGBoost, performed best (AUC = 0.895, sensitivity = 0.80), and the model with CA153, also by XGBoost, showed the largest specificity 0.98. Among all combinations of tumor markers, the combination of CEA and CA153 achieved the best performance (AUC = 0.921, sensitivity = 0.85) in identifying MPE under the diagnostic model constructed by XGBoost.</p><p><strong>Conclusions: </strong>Diagnostic models for MPE with a combination of multiple tumor markers outperformed the models with a single tumor marker, particularly in sensitivity. Using machine learning methods, especially XGBoost, could comprehensively improve the diagnostic accuracy of MPE.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9670205","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}
Pub Date : 2023-06-01DOI: 10.1177/03936155231169796
Da-Hua Liu, Gui-Min Wen, Chang-Liang Song, Pu Xia
Background: Liver cancer seriously threatens human health. Natural killer (NK) cells are an important part of the innate immune system and have strong anti-tumor ability. Immunotherapy based on NK cells has become a hot topic in the treatment of liver cancer.
Methods: In this study, we checked the serum DKK3 (sDKK3) and circulating CD56bright NK cells using ELISA and flow cytometry, respectively, in the blood of liver cancer patients. The effect on recombinant human DKK3 (rhDKK3) on CD56bright NK cells was analyzed in vitro.
Results: We found low levels of sDKK3 in liver cancer patients and a negative correlation between sDKK3 and circulating CD56bright NK cells. In addition, we found that DKK3 induced the differentiation and improved the cytotoxicity of CD56bright NK cells for the first time. It could be used as an agonist for NK cell-based immunotherapy.
Conclusions: Improving the clinical efficacy of NK cells through DKK3 will become a new strategy for cancer immunotherapy.
{"title":"Effect of secretory DKK3 on circulating CD56<sup>bright</sup> natural killer cells in patients with liver cancer.","authors":"Da-Hua Liu, Gui-Min Wen, Chang-Liang Song, Pu Xia","doi":"10.1177/03936155231169796","DOIUrl":"https://doi.org/10.1177/03936155231169796","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer seriously threatens human health. Natural killer (NK) cells are an important part of the innate immune system and have strong anti-tumor ability. Immunotherapy based on NK cells has become a hot topic in the treatment of liver cancer.</p><p><strong>Methods: </strong>In this study, we checked the serum DKK3 (sDKK3) and circulating CD56<sup>bright</sup> NK cells using ELISA and flow cytometry, respectively, in the blood of liver cancer patients. The effect on recombinant human DKK3 (rhDKK3) on CD56<sup>bright</sup> NK cells was analyzed in vitro.</p><p><strong>Results: </strong>We found low levels of sDKK3 in liver cancer patients and a negative correlation between sDKK3 and circulating CD56<sup>bright</sup> NK cells. In addition, we found that DKK3 induced the differentiation and improved the cytotoxicity of CD56<sup>bright</sup> NK cells for the first time. It could be used as an agonist for NK cell-based immunotherapy.</p><p><strong>Conclusions: </strong>Improving the clinical efficacy of NK cells through DKK3 will become a new strategy for cancer immunotherapy.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9724639","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}
Pub Date : 2023-06-01DOI: 10.1177/03936155231156458
Lei Liu, Yaping Li, Shiying Tang, Bin Yang, Qiming Zhang, Ruotao Xiao, Xiaofei Hou, Cheng Liu, Lulin Ma
Background: The Gleason Score is well correlated with biological behavior and prognosis in prostate adenocarcinoma (PRAD). This study was derived to determine the clinical significance and function of Gleason-Score-related genes in PRAD.
Methods: RNA-sequencing profiles and clinical data were extracted from the The Cancer Genome Atlas PRAD database. The Gleason-Score-related genes were screened out by the Jonckheere-Terpstra rank-based test. The "limma" R package was performed for differentially expressed genes. Next, a Kaplan-Meier survival analysis was performed. Correlation MT1L expression levels with tumor stage, non-tumor tissue stage, radiation therapy, and residual tumor were analyzed. Further, MT1L expression was detected in PRAD cell lines by reverse transcription-quantitative polymerase chain reaction assay. Overexpression of MT1L was constructed and used for cell count kit-8, flow cytometric assay, transwell assay, and wound-healing assay.
Results: Survival analysis showed 15 Gleason-Score-related genes as prognostic biomarkers in PRAD. The high-frequency deletion of MT1L was verified in PRAD. Furthermore, MT1L expression was decreased in PRAD cell lines than RWPE-1 cells, and overexpression of MT1L repressed cell proliferation and migration, and induced apoptosis in PC-3 cells.
Conclusion: Gleason-Score-related MT1L may serve as a biomarker of poor prognostic biomarker in PRAD. In addition, MT1L plays a tumor suppressor in PRAD progression, which is beneficial for PRAD diagnosis and treatment research.
背景:Gleason评分与前列腺腺癌(PRAD)的生物学行为和预后有很好的相关性。本研究旨在确定格里森评分相关基因在PRAD中的临床意义和功能。方法:从the Cancer Genome Atlas PRAD数据库中提取rna测序图谱和临床数据。gleason - score相关基因通过Jonckheere-Terpstra秩基础测试筛选出来。对差异表达基因进行“limma”R包装。接下来,进行Kaplan-Meier生存分析。分析MT1L表达水平与肿瘤分期、非肿瘤组织分期、放疗及残余肿瘤的相关性。此外,通过逆转录-定量聚合酶链反应法检测了MT1L在PRAD细胞系中的表达。构建过表达的MT1L,并将其用于细胞计数试剂盒-8、流式细胞术实验、transwell实验和伤口愈合实验。结果:生存分析显示15个gleason评分相关基因可作为PRAD的预后生物标志物。在PRAD中证实了MT1L的高频缺失。与RWPE-1细胞相比,PRAD细胞中MT1L的表达降低,MT1L的过表达抑制了PC-3细胞的增殖和迁移,诱导了细胞凋亡。结论:与gleason评分相关的MT1L可作为PRAD不良预后的生物标志物。此外,MT1L在PRAD进展中发挥抑瘤作用,有利于PRAD的诊断和治疗研究。
{"title":"Gleason Score-related MT1L as biomarker for prognosis in prostate adenocarcinoma and contribute to tumor progression in vitro.","authors":"Lei Liu, Yaping Li, Shiying Tang, Bin Yang, Qiming Zhang, Ruotao Xiao, Xiaofei Hou, Cheng Liu, Lulin Ma","doi":"10.1177/03936155231156458","DOIUrl":"https://doi.org/10.1177/03936155231156458","url":null,"abstract":"<p><strong>Background: </strong>The Gleason Score is well correlated with biological behavior and prognosis in prostate adenocarcinoma (PRAD). This study was derived to determine the clinical significance and function of Gleason-Score-related genes in PRAD.</p><p><strong>Methods: </strong>RNA-sequencing profiles and clinical data were extracted from the The Cancer Genome Atlas PRAD database. The Gleason-Score-related genes were screened out by the Jonckheere-Terpstra rank-based test. The \"limma\" R package was performed for differentially expressed genes. Next, a Kaplan-Meier survival analysis was performed. Correlation MT1L expression levels with tumor stage, non-tumor tissue stage, radiation therapy, and residual tumor were analyzed. Further, MT1L expression was detected in PRAD cell lines by reverse transcription-quantitative polymerase chain reaction assay. Overexpression of MT1L was constructed and used for cell count kit-8, flow cytometric assay, transwell assay, and wound-healing assay.</p><p><strong>Results: </strong>Survival analysis showed 15 Gleason-Score-related genes as prognostic biomarkers in PRAD. The high-frequency deletion of MT1L was verified in PRAD. Furthermore, MT1L expression was decreased in PRAD cell lines than RWPE-1 cells, and overexpression of MT1L repressed cell proliferation and migration, and induced apoptosis in PC-3 cells.</p><p><strong>Conclusion: </strong>Gleason-Score-related MT1L may serve as a biomarker of poor prognostic biomarker in PRAD. In addition, MT1L plays a tumor suppressor in PRAD progression, which is beneficial for PRAD diagnosis and treatment research.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9725159","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}
Pub Date : 2023-06-01DOI: 10.1177/03936155231179981
Francesca Capone, David Morrow, Franca Moretti
Personalized Medicine is a novel medical practice that uses an individual's genetic profile to guide decisions made regarding the prevention, diagnosis, and treatment of disease. Knowledge of a patient's genetic profile is crucial to support doctors in selecting the proper therapy and administer it using the correct dose or regimen. Personalized Medicine is a great opportunity to turn the "one size fits all" approach to diagnostics, therapy, and prevention, into an individualized approach. In this paper we analyze the most recent achievements and regulatory challenges in Personalized Medicine and the role that research infrastructures can play in advancing its development.
{"title":"Ensuring efficient development of personalized medicine by addressing regulatory needs: What role can research infrastructures play?","authors":"Francesca Capone, David Morrow, Franca Moretti","doi":"10.1177/03936155231179981","DOIUrl":"https://doi.org/10.1177/03936155231179981","url":null,"abstract":"<p><p>Personalized Medicine is a novel medical practice that uses an individual's genetic profile to guide decisions made regarding the prevention, diagnosis, and treatment of disease. Knowledge of a patient's genetic profile is crucial to support doctors in selecting the proper therapy and administer it using the correct dose or regimen. Personalized Medicine is a great opportunity to turn the \"one size fits all\" approach to diagnostics, therapy, and prevention, into an individualized approach. In this paper we analyze the most recent achievements and regulatory challenges in Personalized Medicine and the role that research infrastructures can play in advancing its development.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9664044","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}
Pub Date : 2023-03-01DOI: 10.1177/03936155221147536
Ming-Lin Li, Han-Yong Luo, Zi-Wei Quan, Le-Tian Huang, Jia-He Wang
The relationship between PLIN2 expression and prognosis, and clinicopathological significance of various cancers has been extensively studied, but the results are not completely consistent. This review followed the guidelines for systematic reviews of prognostic factors studies and was reported under the Preferred Reporting Program for Systematic Reviews and Meta-Analysis (PRISMA). We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Academia for relevant articles up to September 2, 2022, and calculated the pooled hazard ratios (HR) with 95% confidence intervals (CI) to determine the association between PLIN2 expression and the prognosis of various cancers. The meta-analysis ultimately included 17 studies. The quality of all included cohort studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool, and an adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to assess the certainty of the results. High expression of PLIN2 was associated with poorer overall survival (HR = 1.65; 95% CI = 1.14, 2.38; P = 0.008), metastasis-free survival (HR = 1.48; 95% CI = 1.12, 1.94; P = 0.005), progression-free survival (HR = 2.11; 95% CI = 1.55, 2.87; P < 0.0005) and recurrence-free survival/relapse-free survival (HR = 2.21; 95% CI = 1.64, 2.98; P < 0.0005) in cancers. The clinicopathological parameters of digestive system malignancies suggested that high expression of PLIN2 was notably associated with distant metastasis ( + ) (odds ratio (OR) = 3.37; 95% CI = 1.31, 8.67; P = 0.012), lymph node metastasis ( + ) (OR = 1.61; 95% CI = 1.01, 2.54; P = 0.004), and tumor stage (III-IV) (OR = 1.96; 95% CI = 1.24, 3.09; P = 0.006). In summary, overexpression of PLIN2 is significantly associated with a poor prognosis in various human cancers, especially in respiratory and digestive malignancies. Thus, PLIN2 expression may be a potential prognostic biomarker in cancer patients.
PLIN2表达与预后的关系以及各种癌症的临床病理意义已被广泛研究,但结果并不完全一致。本综述遵循预后因素研究的系统评价指南,并在系统评价和荟萃分析首选报告程序(PRISMA)下进行了报道。我们检索了PubMed、Embase、Cochrane Library、Web of Science和Google Academia截至2022年9月2日的相关文章,并计算了95%可信区间(CI)的合并风险比(HR),以确定PLIN2表达与各种癌症预后之间的关系。荟萃分析最终包括17项研究。使用预后研究质量(QUIPS)工具评估所有纳入的队列研究的质量,并采用推荐分级评估、发展和评价(GRADE)方法评估结果的确定性。PLIN2高表达与较差的总生存率相关(HR = 1.65;95% ci = 1.14, 2.38;P = 0.008), metastasis-free生存(HR = 1.48;95% ci = 1.12, 1.94;P = 0.005),无进展生存(HR = 2.11;95% ci = 1.55, 2.87;P P P = 0.012),淋巴结转移(+)(OR = 1.61;95% ci = 1.01, 2.54;P = 0.004),肿瘤阶段(iii iv) (OR = 1.96;95% ci = 1.24, 3.09;p = 0.006)。综上所述,PLIN2的过表达与各种人类癌症的不良预后显著相关,尤其是呼吸道和消化道恶性肿瘤。因此,PLIN2的表达可能是癌症患者潜在的预后生物标志物。
{"title":"Prognostic and clinicopathologic significance of PLIN2 in cancers: A systematic review with meta-analysis.","authors":"Ming-Lin Li, Han-Yong Luo, Zi-Wei Quan, Le-Tian Huang, Jia-He Wang","doi":"10.1177/03936155221147536","DOIUrl":"https://doi.org/10.1177/03936155221147536","url":null,"abstract":"<p><p>The relationship between PLIN2 expression and prognosis, and clinicopathological significance of various cancers has been extensively studied, but the results are not completely consistent. This review followed the guidelines for systematic reviews of prognostic factors studies and was reported under the Preferred Reporting Program for Systematic Reviews and Meta-Analysis (PRISMA). We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Academia for relevant articles up to September 2, 2022, and calculated the pooled hazard ratios (HR) with 95% confidence intervals (CI) to determine the association between PLIN2 expression and the prognosis of various cancers. The meta-analysis ultimately included 17 studies. The quality of all included cohort studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool, and an adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to assess the certainty of the results. High expression of PLIN2 was associated with poorer overall survival (HR = 1.65; 95% CI = 1.14, 2.38; <i>P</i> = 0.008), metastasis-free survival (HR = 1.48; 95% CI = 1.12, 1.94; <i>P</i> = 0.005), progression-free survival (HR = 2.11; 95% CI = 1.55, 2.87; <i>P</i> < 0.0005) and recurrence-free survival/relapse-free survival (HR = 2.21; 95% CI = 1.64, 2.98; <i>P</i> < 0.0005) in cancers. The clinicopathological parameters of digestive system malignancies suggested that high expression of PLIN2 was notably associated with distant metastasis ( + ) (odds ratio (OR) = 3.37; 95% CI = 1.31, 8.67; <i>P</i> = 0.012), lymph node metastasis ( + ) (OR = 1.61; 95% CI = 1.01, 2.54; <i>P</i> = 0.004), and tumor stage (III-IV) (OR = 1.96; 95% CI = 1.24, 3.09; <i>P</i> = 0.006). In summary, overexpression of PLIN2 is significantly associated with a poor prognosis in various human cancers, especially in respiratory and digestive malignancies. Thus, PLIN2 expression may be a potential prognostic biomarker in cancer patients.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9230897","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}
Pub Date : 2023-03-01DOI: 10.1177/03936155221149749
Esraa Al-Khateeb, Manal A Abbas, Majd B Khader, Maher A Sughayer
Background: Programmed death-ligand 1 (PD-L1) expression in some tumors has prognostic implications. This work aims at investigating PD-L1 expression in diffuse large B-cell lymphoma (DLBCL) and to study its association with clinicopathological variables.
Methods: The study consisted of 75 DLBCL patients who were cared for at the King Hussein Cancer Center during the period 2015-2018. The expression of PD-L1 in tumor tissue was assessed by immunohistochemistry using the anti-human PD-L1 (Clone 22C3) monoclonal antibody. The correlation between gender, age, clinical stage, pre-treatment-LDH level, tumor location, response to therapy, overall and event-free survival with PD-L1 expression was studied.
Results: Six patients were excluded from further analysis as they were in relapse at the time of tissue sampling. The tumor proportion score (TPS) was ≥1% in 16/69 (23.2%) of DLBCL cases while the combined positive score (CPS) at a cut-off of ≥20 was observed in 23/69 (33.3%) cases. No significant difference in PD-L1 expression was found between germinal center B-cell-like (GCB) and non-GCB subtypes. Similarly, no differences in PD-L1 expression (at CPS ≥20 and TPS ≥1) were found between different genders, age groups, clinical stages, tumor location, and patient response to therapy. However, base-line lactate dehydrogenase was significantly elevated in patients with PD-L1 CPS ≥20. The overall survival was not significantly different between PD-L1-positive and -negative groups. On the other hand, the median event-free survival was higher in either of the PD-L1 TPS or CPS negative groups at 107months each versus 54 months in the PD-L1 positive group of either category.
Conclusions: PD-L1 expression can predict event-free survival in DLBCL cases and therefore poor prognosis.
{"title":"Programmed death-ligand 1 expression in diffuse large B-cell lymphoma is associated with poor prognosis.","authors":"Esraa Al-Khateeb, Manal A Abbas, Majd B Khader, Maher A Sughayer","doi":"10.1177/03936155221149749","DOIUrl":"https://doi.org/10.1177/03936155221149749","url":null,"abstract":"<p><strong>Background: </strong>Programmed death-ligand 1 (PD-L1) expression in some tumors has prognostic implications. This work aims at investigating PD-L1 expression in diffuse large B-cell lymphoma (DLBCL) and to study its association with clinicopathological variables.</p><p><strong>Methods: </strong>The study consisted of 75 DLBCL patients who were cared for at the King Hussein Cancer Center during the period 2015-2018. The expression of PD-L1 in tumor tissue was assessed by immunohistochemistry using the anti-human PD-L1 (Clone 22C3) monoclonal antibody. The correlation between gender, age, clinical stage, pre-treatment-LDH level, tumor location, response to therapy, overall and event-free survival with PD-L1 expression was studied.</p><p><strong>Results: </strong>Six patients were excluded from further analysis as they were in relapse at the time of tissue sampling. The tumor proportion score (TPS) was ≥1% in 16/69 (23.2%) of DLBCL cases while the combined positive score (CPS) at a cut-off of ≥20 was observed in 23/69 (33.3%) cases. No significant difference in PD-L1 expression was found between germinal center B-cell-like (GCB) and non-GCB subtypes. Similarly, no differences in PD-L1 expression (at CPS ≥20 and TPS ≥1) were found between different genders, age groups, clinical stages, tumor location, and patient response to therapy. However, base-line lactate dehydrogenase was significantly elevated in patients with PD-L1 CPS ≥20. The overall survival was not significantly different between PD-L1-positive and -negative groups. On the other hand, the median event-free survival was higher in either of the PD-L1 TPS or CPS negative groups at 107months each versus 54 months in the PD-L1 positive group of either category.</p><p><strong>Conclusions: </strong>PD-L1 expression can predict event-free survival in DLBCL cases and therefore poor prognosis.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9237414","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}