Pub Date : 2017-01-01Epub Date: 2017-02-27DOI: 10.14800/ccm.1511
Jerzy Bazak, Jonathan M Fahey, Katarzyna Wawak, Witold Korytowski, Albert W Girotti
Ionizing radiation of specifically targeted cells in a given population is known to elicit pro-death or pro-survival responses in non-targeted bystander cells, which often make no physical contact with the targeted ones. We have recently demonstrated a similar phenomenon for non-ionizing photodynamic therapy (PDT), showing that prostate cancer cells subjected to targeted photodynamic stress stimulated growth and migration of non-stressed, non-contacting bystander cells. Diffusible nitric oxide (NO) generated by stress-upregulated inducible nitric oxide synthase (iNOS) was shown to play a dominant role in these responses. Moreover, target-derived NO stimulated iNOS/NO induction in bystanders, suggesting a NO-mediated feed-forward field effect driven by targeted cells surviving the photodynamic challenge. In this research highlight, we will review these findings and discuss their potential negative implications on clinical PDT outcomes and how these might be mitigated through pharmacologic use of select iNOS inhibitors.
{"title":"Bystander effects of nitric oxide in anti-tumor photodynamic therapy.","authors":"Jerzy Bazak, Jonathan M Fahey, Katarzyna Wawak, Witold Korytowski, Albert W Girotti","doi":"10.14800/ccm.1511","DOIUrl":"https://doi.org/10.14800/ccm.1511","url":null,"abstract":"<p><p>Ionizing radiation of specifically targeted cells in a given population is known to elicit pro-death or pro-survival responses in non-targeted bystander cells, which often make no physical contact with the targeted ones. We have recently demonstrated a similar phenomenon for non-ionizing photodynamic therapy (PDT), showing that prostate cancer cells subjected to targeted photodynamic stress stimulated growth and migration of non-stressed, non-contacting bystander cells. Diffusible nitric oxide (NO) generated by stress-upregulated inducible nitric oxide synthase (iNOS) was shown to play a dominant role in these responses. Moreover, target-derived NO stimulated iNOS/NO induction in bystanders, suggesting a NO-mediated feed-forward field effect driven by targeted cells surviving the photodynamic challenge. In this research highlight, we will review these findings and discuss their potential negative implications on clinical PDT outcomes and how these might be mitigated through pharmacologic use of select iNOS inhibitors.</p>","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708575/pdf/nihms922161.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35613098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Westphalen, B. Renz, M. Reichert, A. Rustgi, T. Wang
Pancreatic regeneration in response to tissue injury is a complex process. Recent progress in the understanding of this process has underscored the need for cellular plasticity as a prerequisite in the course of regeneration. A number of different pancreatic cell types have been proposed as progenitors, stem cells or differentiated cells with a high degree of plasticity. Moreover, in the setting of an oncogenic mutation, similar mechanisms appear to drive pancreatic tumorigenesis. Here, we aim to summarize the recent advances in our understanding of cellular plasticity in the setting of regeneration and tumorigenesis.
{"title":"Cellular plasticity and heterogeneity in pancreatic regeneration and malignancy","authors":"C. Westphalen, B. Renz, M. Reichert, A. Rustgi, T. Wang","doi":"10.14800/CCM.1472","DOIUrl":"https://doi.org/10.14800/CCM.1472","url":null,"abstract":"Pancreatic regeneration in response to tissue injury is a complex process. Recent progress in the understanding of this process has underscored the need for cellular plasticity as a prerequisite in the course of regeneration. A number of different pancreatic cell types have been proposed as progenitors, stem cells or differentiated cells with a high degree of plasticity. Moreover, in the setting of an oncogenic mutation, similar mechanisms appear to drive pancreatic tumorigenesis. Here, we aim to summarize the recent advances in our understanding of cellular plasticity in the setting of regeneration and tumorigenesis.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84512463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The mitogen-activated protein kinase (MAPK) family includes ERK1/2, p38, JNK and ERK5. The role of MAPKs in colorectal cancer (CRC) is well-established, in particular ERK1/2. Abnormal activation of receptor tyrosine kinases or gain-of-function mutations in critical upstream transducers, including KRAS and BRAF, are responsible for MAPK-mediated tumor progression in CRC. Compared to ERK1/2, the role of ERK5 in CRC development has been underrated. Here we discuss recent evidence for the involvement of ERK5 signaling in the development and progression of CRC, as well as its putative role in resistance to targeted therapy.
{"title":"The role of ERK5 signaling in colorectal cancer","authors":"K. Taniguchi, P. R. D. Jong","doi":"10.14800/CCM.1437","DOIUrl":"https://doi.org/10.14800/CCM.1437","url":null,"abstract":"The mitogen-activated protein kinase (MAPK) family includes ERK1/2, p38, JNK and ERK5. The role of MAPKs in colorectal cancer (CRC) is well-established, in particular ERK1/2. Abnormal activation of receptor tyrosine kinases or gain-of-function mutations in critical upstream transducers, including KRAS and BRAF, are responsible for MAPK-mediated tumor progression in CRC. Compared to ERK1/2, the role of ERK5 in CRC development has been underrated. Here we discuss recent evidence for the involvement of ERK5 signaling in the development and progression of CRC, as well as its putative role in resistance to targeted therapy.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82300876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Membrane receptors play important roles in regulating cellular activities. Targeting membrane receptors in cancer cells and understanding their interactions with specific ligands are key for cancer prognosis and therapeutics. However, there is a need to develop new technologies to provide molecular insight into ligand-receptor binding chemistry in cell membrane. Integrin receptors are important membrane receptors that regulate cellular migration, invasion and proliferation in tumors. Integrins have a well-known affinity towards small peptide ligands containing arginine-glycine-aspartate (RGD) sequence and are therefore an attractive model system to study ligand-receptor interactions. We have recently reported a method to detect integrin receptors and study their binding chemistry with cyclic-RGDfC ligand using tip-enhanced Raman scattering (TERS). We have demonstrated that two integrins with similar structures can be differentiated in intact cell membrane, due to the differences in their RGD ligand binding sites, showing the potential of this TERS methodology to study other membrane receptors and their interactions in live cells.
{"title":"Targeted-TERS detection of integrin receptors on human cancer cells.","authors":"Lifu Xiao, Zachary D. Schultz","doi":"10.14800/CCM.1419","DOIUrl":"https://doi.org/10.14800/CCM.1419","url":null,"abstract":"Membrane receptors play important roles in regulating cellular activities. Targeting membrane receptors in cancer cells and understanding their interactions with specific ligands are key for cancer prognosis and therapeutics. However, there is a need to develop new technologies to provide molecular insight into ligand-receptor binding chemistry in cell membrane. Integrin receptors are important membrane receptors that regulate cellular migration, invasion and proliferation in tumors. Integrins have a well-known affinity towards small peptide ligands containing arginine-glycine-aspartate (RGD) sequence and are therefore an attractive model system to study ligand-receptor interactions. We have recently reported a method to detect integrin receptors and study their binding chemistry with cyclic-RGDfC ligand using tip-enhanced Raman scattering (TERS). We have demonstrated that two integrins with similar structures can be differentiated in intact cell membrane, due to the differences in their RGD ligand binding sites, showing the potential of this TERS methodology to study other membrane receptors and their interactions in live cells.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"107 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78626562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tissue inhibitors of metalloproteinases (TIMPs) have been known to be involved in tumorigenesis in both matrix metalloproteinase (MMP)-dependent and MMP-independent manner. This manuscript highlights key findings from our recent research describing the mechanism by which TIMP-2 stimulates lung adenocarcinoma cell proliferation. Our study showed for the first time that TIMP-2 induces lung adenocarcinoma cell proliferation through c-Src kinase activation, independent of MMP inhibition. c-Src kinase activity, induced by TIMP-2, concomitantly increased FAK, phosphoinositide 3-kinase (PI3-kinase)/AKT, and ERK1/2 activation. Furthermore, we showed from multiple cohorts that high TIMP-2 expression in lung adenocarcinomas is associated with a worse prognosis, especially for stage I lung adenocarcinoma. Through integrated analysis of The Cancer Genome Atlas data, Reverse Phase Protein Assay data showed that Src phosphorylation at Y418 significantly increased when TIMP-2 was highly expressed. TIMP-2 expression was significantly associated with the alteration of driving genes and activation of the PI3-kinase/AKT pathway. Taken together, our results suggest that TIMP-2 may play a key role in tumorigenesis of lung adenocarcinoma.
已知金属蛋白酶组织抑制剂(TIMPs)以基质金属蛋白酶(MMP)依赖性和非依赖性两种方式参与肿瘤发生。这篇论文强调了我们最近研究的关键发现，描述了TIMP-2刺激肺腺癌细胞增殖的机制。我们的研究首次表明TIMP-2通过c-Src激酶激活诱导肺腺癌细胞增殖，不依赖于MMP的抑制。TIMP-2诱导的c-Src激酶活性，伴随着FAK、磷酸肌苷3激酶(pi3激酶)/AKT和ERK1/2活化的升高。此外，我们从多个队列中发现，肺腺癌中TIMP-2的高表达与较差的预后相关，特别是对于I期肺腺癌。通过对The Cancer Genome Atlas数据的综合分析，Reverse Phase Protein Assay数据显示，当TIMP-2高表达时，Src在Y418位点的磷酸化显著增加。TIMP-2的表达与驱动基因的改变和pi3激酶/AKT通路的激活显著相关。综上所述，我们的研究结果表明TIMP-2可能在肺腺癌的肿瘤发生中起关键作用。
{"title":"TIMP-2 stimulates cell proliferation through c-Src activation, which influences a worse prognosis for pathological stage I lung adenocarcinoma","authors":"Seo Jin Lee","doi":"10.14800/CCM.1406","DOIUrl":"https://doi.org/10.14800/CCM.1406","url":null,"abstract":"Tissue inhibitors of metalloproteinases (TIMPs) have been known to be involved in tumorigenesis in both matrix metalloproteinase (MMP)-dependent and MMP-independent manner. This manuscript highlights key findings from our recent research describing the mechanism by which TIMP-2 stimulates lung adenocarcinoma cell proliferation. Our study showed for the first time that TIMP-2 induces lung adenocarcinoma cell proliferation through c-Src kinase activation, independent of MMP inhibition. c-Src kinase activity, induced by TIMP-2, concomitantly increased FAK, phosphoinositide 3-kinase (PI3-kinase)/AKT, and ERK1/2 activation. Furthermore, we showed from multiple cohorts that high TIMP-2 expression in lung adenocarcinomas is associated with a worse prognosis, especially for stage I lung adenocarcinoma. Through integrated analysis of The Cancer Genome Atlas data, Reverse Phase Protein Assay data showed that Src phosphorylation at Y418 significantly increased when TIMP-2 was highly expressed. TIMP-2 expression was significantly associated with the alteration of driving genes and activation of the PI3-kinase/AKT pathway. Taken together, our results suggest that TIMP-2 may play a key role in tumorigenesis of lung adenocarcinoma.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82046018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Steele, N. Jamieson, C. Carter, O. Sansom, J. Morton
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy. Therapies targeted against stromal targets in the tumour microenvironment are now in pre-clinical and clinical trial. Here, we focus on our recent findings in autochthonous models of PDAC that suggest CXCR2 expressed on neutrophils is important in establishing immunosuppression in the primary tumour and the metastatic niche at distant sites. We discuss CXCR2 as a potential therapeutic target in the context of other potential stromal targets in PDAC.
{"title":"Anti-CXCR2 directed therapy unmasks the potential for immunotherapy in pancreatic ductal adenocarcinoma","authors":"C. Steele, N. Jamieson, C. Carter, O. Sansom, J. Morton","doi":"10.14800/CCM.1400","DOIUrl":"https://doi.org/10.14800/CCM.1400","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy. Therapies targeted against stromal targets in the tumour microenvironment are now in pre-clinical and clinical trial. Here, we focus on our recent findings in autochthonous models of PDAC that suggest CXCR2 expressed on neutrophils is important in establishing immunosuppression in the primary tumour and the metastatic niche at distant sites. We discuss CXCR2 as a potential therapeutic target in the context of other potential stromal targets in PDAC.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87609610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glioblastoma (GBM) is a highly malignant brain tumor. The GBM tumor mass contains a unique cell population, GBM stem cells (GBM-SCs), which possess the self-renewal, tumor initiating and tumor progression. FGF1B is the major transcriptional variant of FGF1 in GBM. In our recent study, we demonstrated the FGF1B transcript is up-regulated in self-renewing GBM cells. In order to study GBM-SCs, we developed an approach to isolate GBM-SCs by using FGF1B promoter-driven GFP reporter (F1BGFP). We showed that F1BGFP(+) GBM cells exhibit higher phosphorylation levels of FGFR and AurA than F1BGFP(-) cells, indicating the activation of FGFR and AurA. In this research highlight, we summarized the role of FGF1 signaling and AurA in tumorigenesis. In addition, we also suggested that FGF1-FGFR-AurA cascade regulates GBM-SCs, which may enable development of target-based therapy that act against the GBM-SCs.
{"title":"FGF1 signaling regulates self-renewal of glioblastoma stem cells through activation of aurora a kinase","authors":"Chien-Yu Kao, Yi-Chao Hsu, I. Chiu","doi":"10.14800/CCM.1389","DOIUrl":"https://doi.org/10.14800/CCM.1389","url":null,"abstract":"Glioblastoma (GBM) is a highly malignant brain tumor. The GBM tumor mass contains a unique cell population, GBM stem cells (GBM-SCs), which possess the self-renewal, tumor initiating and tumor progression. FGF1B is the major transcriptional variant of FGF1 in GBM. In our recent study, we demonstrated the FGF1B transcript is up-regulated in self-renewing GBM cells. In order to study GBM-SCs, we developed an approach to isolate GBM-SCs by using FGF1B promoter-driven GFP reporter (F1BGFP). We showed that F1BGFP(+) GBM cells exhibit higher phosphorylation levels of FGFR and AurA than F1BGFP(-) cells, indicating the activation of FGFR and AurA. In this research highlight, we summarized the role of FGF1 signaling and AurA in tumorigenesis. In addition, we also suggested that FGF1-FGFR-AurA cascade regulates GBM-SCs, which may enable development of target-based therapy that act against the GBM-SCs.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79308763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Quintanilla, Patricia Carrasco-Ramírez, Lucía Montero-Montero, A. Ramírez-López, I. L. D. Silva, J. Renart, Ester Martín-Villar
Podoplanin (PDPN) is a small mucin-like glycoprotein upregulated in a variety of cancers where it can be expressed in tumor as well as in stromal cells, such as cancer associated fibroblasts (CAFs). In most cancers, especially in squamous cell carcinomas (SCC) and glioblastomas, PDPN expression is associated with increased risk of metastasis to lymph nodes and reduced overall survival, although the opposite has been found in other tumor types. Studies from different laboratories, including our own, suggest that PDPN is involved in different steps of the metastatic cascade. Thus, PDPN, which is connected to the actin cytoskeleton through the binding to ezrin and/or moesin, stimulates collective tumor cell migration/invasion, and induces an epithelial-mesenchymal transition allowing a directional migration of individual cells through its interaction with the hyaluronan receptor CD44. PDPN is a component of the invadopodium contributing to its stability and promoting an efficient invasion through the extracellular matrix. In addition, PDPN favors the survival of cancer cells in the bloodstream aiding to their metastatic dissemination by inducing platelet aggregation/activation through its binding to the platelet receptor CLEC-2. More recently, we have reported that PDPN is a component of microvesicles and exosomes released by tumor cells and that PDPN-containing exosomes enhance in vitro lymphangiogenesis. In this short review, we discuss the role of PDPN in all these processes that foster malignant progression.
{"title":"Podoplanin promotes malignancy through a diversity of strategies","authors":"M. Quintanilla, Patricia Carrasco-Ramírez, Lucía Montero-Montero, A. Ramírez-López, I. L. D. Silva, J. Renart, Ester Martín-Villar","doi":"10.14800/CCM.1384","DOIUrl":"https://doi.org/10.14800/CCM.1384","url":null,"abstract":"Podoplanin (PDPN) is a small mucin-like glycoprotein upregulated in a variety of cancers where it can be expressed in tumor as well as in stromal cells, such as cancer associated fibroblasts (CAFs). In most cancers, especially in squamous cell carcinomas (SCC) and glioblastomas, PDPN expression is associated with increased risk of metastasis to lymph nodes and reduced overall survival, although the opposite has been found in other tumor types. Studies from different laboratories, including our own, suggest that PDPN is involved in different steps of the metastatic cascade. Thus, PDPN, which is connected to the actin cytoskeleton through the binding to ezrin and/or moesin, stimulates collective tumor cell migration/invasion, and induces an epithelial-mesenchymal transition allowing a directional migration of individual cells through its interaction with the hyaluronan receptor CD44. PDPN is a component of the invadopodium contributing to its stability and promoting an efficient invasion through the extracellular matrix. In addition, PDPN favors the survival of cancer cells in the bloodstream aiding to their metastatic dissemination by inducing platelet aggregation/activation through its binding to the platelet receptor CLEC-2. More recently, we have reported that PDPN is a component of microvesicles and exosomes released by tumor cells and that PDPN-containing exosomes enhance in vitro lymphangiogenesis. In this short review, we discuss the role of PDPN in all these processes that foster malignant progression.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75946341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive molecules present in the tumor milieu are known to contribute substantially to tumor progression. Phospholipid mediators are a group of molecules that have roles in normal physiology as well as in pathological conditions. Platelet activating factor (PAF), a phospholipd mediator, secreted by cells present in tumor microenvironment has been implicated to have a possible role in cancer progression. Here, we highlight our study of the potential role of PAF in inducing transformation of breast epithelial cells grown as three dimensional cultures. We have also attempted to dissect the motility related molecular pathway activated upon PAF stimulation in MDA-MB 231 cells. This study further calls for detailed analysis of pathways downstream of PAF signalling which would aid in identification of targets and designing of treatment strategies.
{"title":"Platelet activating factor leads to initiation and promotion of breast cancer","authors":"Libi Anandi, M. Lahiri","doi":"10.14800/CCM.1370","DOIUrl":"https://doi.org/10.14800/CCM.1370","url":null,"abstract":"Bioactive molecules present in the tumor milieu are known to contribute substantially to tumor progression. Phospholipid mediators are a group of molecules that have roles in normal physiology as well as in pathological conditions. Platelet activating factor (PAF), a phospholipd mediator, secreted by cells present in tumor microenvironment has been implicated to have a possible role in cancer progression. Here, we highlight our study of the potential role of PAF in inducing transformation of breast epithelial cells grown as three dimensional cultures. We have also attempted to dissect the motility related molecular pathway activated upon PAF stimulation in MDA-MB 231 cells. This study further calls for detailed analysis of pathways downstream of PAF signalling which would aid in identification of targets and designing of treatment strategies.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89365918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colorectal cancer (CRC) is the third most common cancer in the world and it is a determinant cause of mortality. A significant survival rate is achieved if the disease is detected at an early stage, thus screening represents an important cancer-control tool. Recently we unveiled a panel of mRNAs, which if isolated in whole blood represent an efficient screening test for colorectal cancer. These mRNA molecules as a biomarker in blood by qRT-PCR assay offer a test with high sensitivity and specificity for clinical diagnostics. The expression of 4 genes: TSPAN8, LGALS4, COL1A2 and CEACAM6 proved to be statistically different between patients and healthy controls. The diagnostic accuracy, in terms of specificity and sensitivity of the TSPAN8 and LGALS4 combination, displayed a sensitivity of 92.5% and a specificity of 67.2%. Our preliminary study was validated on a cohort of 134 subjects and it showed promising results for a prognostic test of blood screening. Nevertheless, it needs to be validated in a larger cohort with stage stratification and in patients with other gastrointestinal diseases.
{"title":"TSPAN8 and LGALS4 combination as blood biomarkers for colorectal cancer detection","authors":"M. T. Rodia, R. Solmi, Lauriola Mattia","doi":"10.14800/CCM.1366","DOIUrl":"https://doi.org/10.14800/CCM.1366","url":null,"abstract":"Colorectal cancer (CRC) is the third most common cancer in the world and it is a determinant cause of mortality. A significant survival rate is achieved if the disease is detected at an early stage, thus screening represents an important cancer-control tool. Recently we unveiled a panel of mRNAs, which if isolated in whole blood represent an efficient screening test for colorectal cancer. These mRNA molecules as a biomarker in blood by qRT-PCR assay offer a test with high sensitivity and specificity for clinical diagnostics. The expression of 4 genes: TSPAN8, LGALS4, COL1A2 and CEACAM6 proved to be statistically different between patients and healthy controls. The diagnostic accuracy, in terms of specificity and sensitivity of the TSPAN8 and LGALS4 combination, displayed a sensitivity of 92.5% and a specificity of 67.2%. Our preliminary study was validated on a cohort of 134 subjects and it showed promising results for a prognostic test of blood screening. Nevertheless, it needs to be validated in a larger cohort with stage stratification and in patients with other gastrointestinal diseases.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76782072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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