Circulating tumor cells in pancreatic cancer:The prognostic impact in surgical patients

Pancreatic cancer is associated with a poor prognosis,even in the early stages,mainly due to metastatic progression.New diagnostic techniques that predict unfavorable outcomes are needed in order to improve treatment strategies.Circulating tumor cells(CTCs)are showing promising results as a predictive biomarker for various tumors.In this editorial we comment on the article by Zhang et al,who published the first systematic review and meta-analysis evaluating the prognostic value of CTCs as biomarkers in early-stage pancreatic cancer patients undergoing surgery.CTCs were detected in peripheral or central venous system blood,before or during surgery.Positive CTCs showed a correlation with decreased overall survival and decreased relapse-free,disease-free and progression-free survival in this meta-analysis.However,the heterogeneity was significant.The authors suggest that this result was related to the separation methods used between studies,but other differences such as the margin status or the neoadjuvant and adjuvant treatments used are also important to consider.CTCs may be a potential prognostic biomarker in pancreatic cancer patients,but it is necessary to compare and standardize the platforms used to isolate CTCs,to compare different biomarkers from liquid biopsy and to determine the impact on prognosis when therapeutic changes are made based on CTCs levels.

Circulating tumor cells as prognostic marker in pancreatic cancer

In this editorial we comment on the article by Zhang et al published in the recent issue of the World Journal of Clinical Oncology.Pancreatic cancer is the fourth most common cause of cancer-related mortality and has the lowest survival rate among all solid cancers.It causes 227000 deaths annually worldwide,and the 5-year survival rate is very low due to early metastasis,which is 4.6%.Cancer survival increases with better knowledge of risk factors and early and accurate diagnosis.Circulating tumor cells(CTCs)are tumor cells that intravasate from the primary tumor or metastasis foci into the peripheral blood circulation system spontan-eously or during surgical operations.Detection of CTC in blood is promising for early diagnosis.In addition,studies have associated high CTC levels with a more advanced stage,and more intensive treatments should be considered in cases with high CTC.In tumors that are considered radiologically resectable,it may be of critical importance in detecting occult metastases and preventing unnecessary surgeries.

Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response

AIM: To evaluate the epithelial-to-mesenchymal transition(EMT) of circulating tumor cells(CTCs) in gastric cancer patients.METHODS: We detected tumor cells for expression of four epithelial(E^+) transcripts(keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal(M^+) transcripts(Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6^(th) cycle of XELOX based chemotherapy(about 6 mo postoperatively)].RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E^+/M^+ cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35(79.5%) patients at baseline. Five types of cells including from exclusively E^+ CTCs to intermediate CTCs and exclusively M^+ CTCs were identified(4 patients with M^+ CTCs and 10 patients with M^+ or M^+ > E^+ CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of Can Patrol^(TM) system and the correlation coefficient(R^2) was 0.999.CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.

Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells

Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Circulating tumor cells(CTCs) or other blood biomarkers that are released into the circulating blood stream by tumors are thought to play a crucial role in the recurrence and metastasis of gastric cancer. Therefore, the detection of CTCs and other blood biomarkers has an important clinical significance; in fact, they can help predict the prognosis, assess the staging, monitor the therapeutic effects and determine the drug susceptibility. Recent research has identified many blood biomarkers in GC, such as various serum proteins, autoantibodies against tumor associated antigens, and cell-free DNAs. The analysis of CTCs and circulating cell-free tumor DNA(ctDNA) in the peripheral blood of patients with gastric cancer is called as liquid biopsy. These blood biomarkers provide the disease status for individuals and have clinical meaning. In this review, we focus on the recent scientific advances regarding CTCs and other blood biomarkers, and discuss their origins and clinical meaning.

Aneuploidy of chromosome 8 in circulating tumor cells correlates with prognosis in patients with advanced gastric cancer

Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients＇ clinical prognosis.Methods： The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment（SE） and immunostaining-fluorescence in situ hybridization（i FISH）platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.Results： CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 m L and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival（PFS） and overall survival（OS）. In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.Conclusions： Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.

Cryopreservation for delayed circulating tumor cell isolation is a valid strategy for prognostic association of circulating tumor cells in gastroesophageal cancer

AIM To demonstrate the feasibility of cryopreservation of peripheral blood mononuclear cells(PBMCs) for prognostic circulating tumor cell(CTC) detection in gastroesophageal cancer.METHODS Using 7.5 m L blood samples collected in EDTA tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by epithelial cell adhesion molecule based immunomagnetic capture using the Iso Flux platform. Paired specimens taken during the same blood draw(n = 15) were used to compare number of CTCs isolated from fresh and cryopreserved PBMCs. Blood samples were processed within 24 h to recover the PBMC fraction, with PBMCs used for fresh analysis immediately processed for CTC isolation. Cryopreservation of PBMCs lasted from 2 wk to 25.2 mo(median 14.6 mo). CTCs isolated from pre-treatment cryopreserved PBMCs(n = 43) were examined for associations with clinicopathological variables and survival outcomes.RESULTS While there was a significant trend to a decrease in CTC numbers associated with cryopreserved specimens(mean number of CTCs 34.4 vs 51.5, P = 0.04), this was predominately in samples with a total CTC count of > 50, with low CTC count samples less affected(P = 0.06). There was no significant association between the duration of cryopreservation and number of CTCs. In cryopreserved PBMCs from patient samples prior to treatment, a high CTC count(> 17) was associated with poorer overall survival(OS)(n = 43, HR = 4.4, 95%CI: 1.7-11.7, P = 0.0013). In multivariate analysis, after controlling for sex, age, stage, ECOG performance status, and primary tumor location, a high CTC count remained significantly associated with a poorer OS(HR = 3.7, 95%CI: 1.2-12.4, P = 0.03). CONCLUSION PBMC cryopreservation for delayed CTC isolation is a valid strategy to assist with sample collection, transporting and processing.

Liquid biopsy of gastric cancer patients:Circulating tumor cells and cell-free nucleic acids

To improve the clinical outcomes of cancer patients, early detection and accurate monitoring of diseases are necessary. Numerous genetic and epigenetic alterations contribute to oncogenesis and cancer progression, and analyses of these changes have been increasingly utilized for diagnostic, prognostic and therapeutic purposes in malignant diseases including gastric cancer (GC). Surgical and/or biopsy specimens are generally used to understand the tumor-associated alterations; however, those approaches cannot always be performed because of their invasive characteristics and may fail to reflect current tumor dynamics and drug sensitivities, which may change during the therapeutic process. Therefore, the importance of developing a non-invasive biomarker with the ability to monitor real-time tumor dynamics should be emphasized. This concept, so called “liquid biopsy”, would provide an ideal therapeutic strategy for an individual cancer patient and would facilitate the development of “tailor-made” cancer management programs. In the blood of cancer patients, the presence and potent utilities of circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) such as DNA, mRNA and microRNA have been recognized, and their clinical relevance is attracting considerable attention. In this review, we discuss recent developments in this research field as well as the relevance and future perspectives of CTCs and cfNAs in cancer patients, especially focusing on GC.

Prognostic value of circulating tumor cells in esophageal cancer

AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells(CTCs) can be used as a prognostic marker of esophageal cancer.METHODS Pub Med, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival(OS). The meta-analysis was performed using the random effects model, with hazard ratio(HR), risk ratio(RR) and 95% confidence intervals(95%CIs) as effect measures.RESULTS Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression(HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS(HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage(RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage(RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer.CONCLUSION Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted.

Incorporation of circulating tumor cells and whole-body metabolic tumor volume of 18F-FDG PET/CT improves prediction of outcome inⅢB stage small-cell lung cancer

Objective: We investigated the correlation between the number of circulating tumor cells(CTCs) and wholebody metabolic tumor volume(WBMTV) measured by 18 F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT).The aim was to evaluate the value of the incorporation of CTC number and WBMTV in the prognostic prediction of stage III small-cell lung cancer(SCLC).Methods: One hundred and twenty-nine patients were enrolled in this study.All patients were treated with four cycles of a platinum-based regimen and concurrent chest irradiation,followed by prophylactic cranial irradiation.Blood samples for CTC analysis were obtained from 112 patients before the initiation of chemotherapy(as a baseline),after cycle 1 and after cycle 4.CTCs were measured using the CELLSEARCH? system.The patients underwent pretreatment FDG PET/CT WBMTV,which included all malignant lesions.The Spearman rank test was used to determine the correlation among CTC counts,WBMTV and disease stage.Overall survival(OS) and progression-free survival(PFS) curves were produced using the Kaplan-Meier method,and survival differences between groups were assessed by the log-rank test.Results: The number of CTCs at baseline did not correlate with WBMTV before the initiation of therapy(P=0.241).The number of CTCs at baseline and the WBMTV before the initiation of therapy were independent relevant factors for PFS and OS.The subgroup analysis(Group A: CTC count >19.5 and a WBMTV >266.5cm~3;Group B: CTC count >19.5 and a WBMTV ≤266.5cm~3; Group C: CTC count ≤19.5 and a WBMTV >266.5cm~3;Group D: CTC count ≤19.5 and a WBMTV ≤266.5cm~3) showed that the differences were statistically significant in the median PFS(Group A vs.D,P<0.001; Group B vs.D,P=0.018; Group C vs.D,P=0.029) and in the median OS(Group A vs.D,P<0.001; Group B vs.D,P=0.012).Conclusions: CTC number and WBMTV are related to progression and death in patients with SCLC.The incorporation of CTC number and WBMTV scans can provide a detailed prognostic prediction for SCLC.

MUC1-positive circulating tumor cells and MUC1 protein predict chemotherapeutic efficacy in the treatment of metastatic breast cancer

Chemotherapy plays an important role in the treatment of metastatic breast cancer. It is important to monitor chemotherapeutic efficacy, to find a simple and efficient tool to guide treatment, and to predict the efficacy of treatment in a timely and accurate manner. This study aimed to detect mucin-1 (MUC1) - positive circulating tumor cells and MUC1 protein in the peripheral blood of patients with metastatic breast cancer and to investigate their relationship to chemotherapeutic efficacy. MUC1 mRNA was detected in the peripheral blood of 34 patients with newly diagnosed metastatic breast cancer by reverse transcription- polymerase chain reaction. The positive rates of MUC1 mRNA were 88.2% before chemotherapy and 70.6% after chemotherapy, without a significant difference (P = 0.564); MUC1 mRNA expression before chemotherapy had no correlation with treatment effectiveness (P = 0.281). The response rate of MUC1 mRNA -negative patients after first-cycle chemotherapy was significantly higher (P = 0.009) and the progression-free survival (PFS) was clearly longer than those of MUC1 mRNA-positive patients (P = 0.095). MUC1 protein in peripheral blood plasma was detected by an ELISA competitive inhibition assay. The patients with decreased MUC1 protein after chemotherapy had a significantly longer PFS than those with elevated MUC1 protein (P = 0.044). These results indicate that the outcomes of MUC1 mRNA - negative patients after chemotherapy are better than those of MUC1 mRNA-positive patients. In addition, patients with decreased expression of MUC1 protein have a better PFS.

Epithelial-mesenchymal transition status of circulating tumor cells in breast cancer and its clinical relevance

Objective:Circulating tumor cells(CTCs)play a critical role in cancer metastasis,but their prevalence and significance remain unclear.This study attempted to track the epithelial-mesenchymal transition(EMT)status of CTCs in breast cancer patients and investigate their clinical relevance.Methods:In this study,the established negFACS-IF:E/M platform was applied to isolate rare CTCs and characterize their EMT status in breast cancer.A total of 89 breast cancer patients were recruited,including stage 0–III(n=60)and late stage(n=29)cases.Results:Using the negFACS-IF:E/M platform,it was found that in human epidermal growth factor receptor 2(HER2)+patients,mesenchymal CTCs usually exhibited a high percentage of HER2+cells.Stage IV breast cancer patients had considerably more CTCs than stage 0–III patients.Among stage 0–III breast cancers,the HER2 subtype included a significantly higher percentage of mesenchymal and biphenotypic(epithelial and mesenchymal)CTCs than the luminal A or B subtypes.Among stage IV patients,CTCs were predominantly epithelial in cases with local recurrence and were more mesenchymal in cases with distant metastasis.By applying a support vector machine(SVM)algorithm,the EMT status of CTCs could distinguish between breast cancer cases with metastasis/local recurrence and those without recurrence.Conclusions:The negFACS-IF:E/M platform provides a flexible and generally acceptable method for the highly sensitive and specific detection of CTCs and their EMT traits in breast cancer.This study demonstrated that the EMT status of CTCs had high clinical relevance in breast cancer,especially in predicting the distant metastasis or local recurrence of breast cancer.

Circulating tumor cells with epithelial-mesenchymal transition markers as potential biomarkers for the diagnosis of lung cancer

BACKGROUND Circulating tumor cells(CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition(EMT) markers: CTCs with epithelial markers(E-CTCs), CTCs with mesenchymal markers(M-CTCs), and CTCs with both markers(E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer(LC).AIM To clarify the diagnostic value of CTCs categorized by EMT markers in LC.METHODS The study included 106 patients with lung adenocarcinoma, including 42 groundglass opacities(GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrol TM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic(ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques.RESULTS Of the 106 LC cases, 94(89.6%) had at least one CTC. CTCs were detectable in 35(83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of MCTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients(80.95% for GGO patients) and the specificity was 78.57%.The Kappa value was 0.415,indicating relative consistency between CanPatrol TM and CytoploRare.CONCLUSION CTC detection is valuable for distinguishing LC from controls,and particularly E&M-CTC detection warrants further study.

Applications of circulating tumor cells for prostate cancer

One of the major challenges that clinicians face is in the difficulties of accurately monitoring disease progression.Prostate cancer is among these diseases and greatly affects the health of men globally.Circulating tumor cells(CTCs)are a rare population of cancer cells that have shed from the primary tumor and entered the peripheral circulation.Not until recently,clinical applications of CTCs have been limited to using enumeration as a prognostic tool in Oncology.However,advances in emerging CTC technologies point toward new applications that could revolutionize the field of prostate cancer.It is now possible to study CTCs as components of a liquid biopsy based on morphological phenotypes,biochemical analyses,and genomic profiling.These advances allow us to gain insight into the heterogeneity and dynamics of cancer biology and to further study the mechanisms behind the evolution of therapeutic resistance.These recent developments utilizing CTCs for clinical applications will greatly impact the future of prostate cancer research and pave the way towards personalized care for men.

Application of Circulating Tumor Cells in Peripheral Blood in Judging the Prognosis of Patients with Renal Cancer and Related Indexes of Blood Coagulation

Objective: To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. Methods: 65 patients with renal cell carcinoma (RCC) confirmed pathologically were divided into CTC positive group and CTC negative group according to the CTC count (5 pcs/3.5 ml). Compare the age, gender, tumor location, TNM (clinical stage), pathological grade, tissue type, lymph node metastasis, distant metastasis, prognosis and prothrombin time (PT), fibrinogen (FIB), partial coagulation of the two groups of patients The correlation between the results of zymogen time (APTT) and D-dimer (DD) and the number of CTC. Results: There were significant differences in TNM, lymph node metastasis, and distant metastasis between the two groups (P < 0.05). The number of CTC in patients was correlated with FIB and D-D levels (P < 0.05). Conclusion: The number of CTC in patients with renal cell carcinoma is correlated with some clinical phenotypes (TNM, lymph node metastasis, distant metastasis) and some coagulation indexes (FIB, D-D), and can jointly predict the prognosis of renal cancer.

Expected clinical applications of circulating tumor cells in breast cancer

Tumor cell invasion and intravascular filtration lead to the presence of circulating tumor cells(CTCs)in peripheral blood.CTCs have,thus,been counted in patients with cancer to analyze metastatic mechanisms or in the hope of developing clinical applications for diagnosis and therapy;various CTC-related studies have been performed.However,the clinical significance of CTCs remains to be established because of the extremely small number of CTCs in peripheral blood as compared with the number of blood cells.Technical problems(e.g.reproducibility and reliability)in the detection of CTCs also remain to be solved.The use of flow cytometric analysis,which can be performed with tumor-cell markers such as anti-epithelial cell adhesion molecule antibodies and anti-cytokeratin antibodies and nontumor-cell markers such as anti-CD45 antibodies has enhanced specificity for the detection of tumor cells.The CellSearch System?can detect 1 CTC in 7.5 mL of peripheral blood,with high reproducibility.Its detection rate and accuracy for CTCs have been confirmed.In the United States,clinical trials have used this system to detect CTCs in patients with metastatic breast cancer,metastatic colorectal cancer,and metastatic prostate cancer,and CTCs have been confirmed to be a useful prognostic factor.This system was also suggested to be useful for monitoring treatment response in patients with metastatic breast cancer and was approved by the United States Food and Drug Administration in 2004.Measuring CTC counts can facilitate the early prediction of treatment response and thereby avoid unnecessary therapy.CTCs may also be a useful biomarker for molecular targeted agents,enabling the identification of patients most likely to respond to a given treatment and facilitating treatment selection.However,the widespread use of CTC monitoring as a routine examination requires a further improvement in measurement sensitivity,the establishment of criteria for quantitative and qualitative evaluations,and additional clear-cut evidence supporting the clinical significance of CTCs.We expect that CTCs will be established to be a new diagnostic and therapeutic index for breast cancer.

Clinical implications and perspectives of portal venous circulating tumor cells in pancreatic cancer

Despite recent improvements in the diagnosis and treatment of pancreatic cancer(PC),clinical outcomes remain dismal.Moreover,there are no effective prognostic or predictive biomarkers or options beyond carbohydrate antigen 19-9 for personalized and precise treatment.Circulating tumor cells(CTCs),as a member of the liquid biopsy family,could be a promising biomarker;however,the rarity of CTCs in peripheral venous blood limits their clinical use.Because the first venous drainage of PC is portal circulation,the portal vein can be a more suitable location for the detection of CTCs.Endoscopic ultrasound-guided portal venous sampling of CTCs is both feasible and safe.Several studies have suggested that the detection rate and number of CTCs may be higher in the portal blood than in the peripheral blood.CTC counts in the portal blood are highly associated with hepatic metastasis,recurrence after surgery,and survival.The phenotypic and genotypic properties measured in the captured portal CTCs can help us to understand tumor heterogeneity and predict the prognosis of PC.Small sample sizes and heterogeneous CTC detection methods limit the studies to date.Therefore,a large number of prospective studies are needed to corroborate portal CTCs as a valid biomarker in PC.

Epithelial-mesenchymal transition contributes to malignant phenotypes of circulating tumor cells derived from gastric cancer

Circulating tumor cells(CTCs)are crucial to tumor metastasis,and they usually undergo epithelial-mesenchymal transition(EMT)in order to disseminate from the primary tumor.However,very little is currently known about the relationship between EMT and malignant phenotypes of CTCs in the context of gastric cancer.Therefore,this study aimed to investigate the contribution of EMT to malignant phenotypes of CTCs derived from gastric cancer cells.We xenografted MKN28 gastric cancer cells pretreated with transforming growth factor-beta 1(TGFβ-1)into nude mice by intravenous injection.Next,we isolated CTCs from the blood of nude mice by gradient centrifugation and found that CTCs derived from MKN28 cells pretreated with TGFβ-1 had a significantly increased viability and invasion ability compared to MKN28 cells without TGFβ-1 treatment.Immunocytochemical staining showed lower expression of E-cadherin and higher expression of N-cadherin,vimentin,and β-catenin in CTCs derived from MKN28 cells pretreated with TGFβ-1.Furthermore,the expression of Wnt3a,β-catenin,cyclin D1,and c-Myc was significantly higher in CTCs derived from MKN28 cells pretreated with TGFβ-1.Taken together,these findings suggest that TGFβ promotes EMT and malignant phenotypes of gastric cancer cells.Furthermore,the malignant phenotypes of gastric cancer cells induced by TGFβ are maintained in CTCs derived from these cells.Targeting EMT in CTCs is a new approach to the treatment of gastric cancer relapse and metastasis.

Detection of Circulating Tumor Cells in Patients with Breast, Prostate, Pancreatic, Colon and Melanoma Cancer: A Blinded Comparative Study Using Healthy Donors

Cancer is a diverse disease characterized by abnormal cell growth and the ability to invade or spread to other parts of the body. Because the yearly cancer rate is increasing, an important area for cancer researchers is to improve the ability to detect and treat cancer early. The current study analyzes the potential of flow cytometry to be used to detect circulating tumor cells (CTCs) in patients with various cancer types and stages. CTCs are cells that have detached from the primary tumor and entered the blood stream in the process of metastasizing to other organs. To determine the accuracy of flow cytometry in detecting CTCs, a comparative study was performed on healthy donors. In this study, blood samples from patients with breast, prostate, pancreatic, colon and skin cancer were analyzed and compared with healthy donors. The data were collected and analyzed statistically with receiver operating characteristic curve analysis. The results indicate that CTCs can be detected in over 83% of the cancer patients and therefore may be a promising method for diagnosing cancer.

Clinicopathological and Prognostic Significance of Circulating Tumor Cells in Patients with Head and Neck Cancer: A Meta-Analysis

Purpose: The aim of the study was to evaluate the association between clinicopathological and prognostic significance and circulating tumor cells (CTCs) in patients with head and neck cancer. Methods: We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between clinicopathological and prognostic significance and CTCs in patients with head and neck cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Results: Seventeen studies with 816 patients were eligible for combined analysis. Presence of CTCs in peripheral blood was significantly associated with N stage (OR 0.50, 95%CI [0.30, 0.81], n = 10, P = 0.005). Patients in the high-CTC group were significantly associated with poorer disease-free survival (DFS;HR = 1.73, 95%CI [1.01 - 2.96], P = 0.050) and poorer overall survival (OS;HR = 2.53, 95%CI [1.37 - 4.69] P = 0.003). Further analyses indicated strong prognostic powers of CTCs in non-RT-PCR group and pre-treatment group. Conclusion: Our meta-analysis indicates that presence of CTCs is associated with higher N stage and poorer prognosis in patients with head and neck cancer. The potential for further clinical application may be needed for further investigation.Purpose: The aim of the study was to evaluate the association between clinicopathological and prognostic significance and circulating tumor cells (CTCs) in patients with head and neck cancer. Methods: We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between clinicopathological and prognostic significance and CTCs in patients with head and neck cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Results: Seventeen studies with 816 patients were eligible for combined analysis. Presence of CTCs in peripheral blood was significantly associated with N stage (OR 0.50, 95%CI [0.30, 0.81], n = 10, P = 0.005). Patients in the high-CTC group were significantly associated with poorer disease-free survival (DFS;HR = 1.73, 95%CI [1.01 - 2.96], P = 0.050) and poorer overall survival (OS;HR = 2.53, 95%CI [1.37 - 4.69] P = 0.003). Further analyses indicated strong prognostic powers of CTCs in non-RT-PCR group and pre-treatment group. Conclusion: Our meta-analysis indicates that presence of CTCs is associated with higher N stage and poorer prognosis in patients with head and neck cancer. The potential for further clinical application may be needed for further investigation.

Development of a Novel Tissue-Specific Method to Detect Cytokeratin 20-Positive Circulating Tumor Cells in Metastatic Colorectal Cancer

Introduction:Although many studies have shown the vast potential of circulating tumor cells(CTCs)detection in cancer diagnosis and prognosis,our understanding of their clinical significance is still far from complete.A major obstacle arises from the lack of well-established tumor or tissue-specific markers to detect CTCs by immunocytochemical staining after immunomagnetic enrichment(IE).Methods:We have established the utility of cytokeratin 20(CK20),a gastrointestinal tract specific marker,for the specific detection and identification of colorectal cancer(CRC)CTCs.This breakthrough was successfully validated in spike-in experiments using CRC cell line models followed by a pilot study which recruited 32 metastatic CRC patients,25 benign colorectal diseases patients and 27 normal subjects.Results:CK20-positive CTCs were detected in 90%metastatic CRC patients but not in benign colorectal diseases patients and normal subjects using this refined assay.Conclusions:These impressive results have laid the foundation for further development of CK20-positive CTCs as a promising marker in diagnosis,prognostication and treatment monitoring of metastatic CRC.