Long-term prognostic impact of circulating tumour cells in gastric cancer patients

AIM To analyse the long-term prognostic impact of circulating tumour cells(CTCs) in gastric cancer patients who underwent surgery. METHODS A 7.5-m L peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerasespecific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated. RESULTS The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-m L of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant(P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs(P = 0.034).CONCLUSION A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer.

Squamous cell carcinoma of the oral cavity and circulating tumour cells

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.

Detection of circulating tumour cells in colorectal cancer:Emerging techniques and clinical implications

Despite several advances in oncological management of colorectal cancer,morbidity and mortality are still high and devastating.The diagnostic evaluation by endoscopy is cumbersome,which is uncomfortable to many.Because of the intra-and inter-tumour heterogeneity and changing tumour dynamics,which is continuous in nature,the diagnostic biopsy and assessment of the pathological sample are difficult and also not adequate.Late manifestation of the disease and delayed diagnosis may lead to relapse or metastases.One of the keys to improving the outcome is early detection of cancer,ease of technology to detect with uniformity,and its therapeutic implications,which are yet to come."Liquid biopsy"is currently the most recent area of interest in oncology,which may provide important tools regarding the characterization of the primary tumour and its metastasis as cancer cells shed into the bloodstream even at the early stages of the disease.By using this approach,clinicians may be able to find out information about the tumour at a given time.Any of the following three types of sampling of biological material can be used in the"liquid biopsy".These are circulating tumour cells(CTCs),circulating tumour DNA,and exosomes.The most commonly studied amongst the three is CTCs.CTCs with their different applications and prognostic value has been found useful in colorectal cancer detection and therapeutics.In this review,we will discuss various markers for CTCs,the core tools/techniques for detection,and also important findings of clinical studies in colorectal cancer and its clinical implications.

Mutational Analysis of OCT4+ and OCT4− Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

Circulating tumour cells(CTCs)were enriched in the peripheral blood of four patients with Stage I non-small cell lung cancer(NSCLC).Octamer-binding transcription factor-4 positive(OCT4+)and negative(OCT4−)CTCs were identified and captured by interphase fluorescence in situ hybridisation(iFISH).Single cell whole exome sequencing(WES)was performed and the corresponding bioinformatics data were analysed.OCT4+cells were successfully detected in peripheral blood collected from all four Stage I lung cancer patients.Moreover,the tumour mutational burden(TMB)values observed for OCT4+samples from the same patients were slightly smaller than those of the OCT4−samples;the difference was not statistically significant(P>0.05).Thirteen and six characteristic mutations were found in negative samples and positive samples,respectively.The findings indicate that this methodology provides a potential diagnostic index for the early detection of NSCLC.

CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules

Background and objective Low-density computed tomography(LDCT)improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data.Hence,accurate diagnosis of early-stage lung cancer remains challenging.The purpose of the study was to assess the feasibility of using circulating tumour cells(CTCs)to differentiate malignant from benign pulmonary nodules.Materials and methods 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited.Peripheral blood samples were collected before surgery,and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis.Laser capture microdissection,MALBAC amplification,and whole-exome sequencing were performed on 8 samples.The diagnostic efficacy of CTCs counting,and the genomic variation profile of benign and malignant CTCs samples were analysed.Results Using 2.5 cells/5 m L as the cut-off value,the area under the receiver operating characteristic curve was of 0.651(95%confidence interval:0.538-0.764),with a sensitivity and specificity of 0.526 and 0.800,respectively,and positive and negative predictive values of 91.1%and 30.3%,respectively.Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples.TP53 mutations were identified in CTCs of four malignant cases;in particular,g.7578115T>C,g.7578645C>T,and g.7579472G>C were exclusively detected in all four malignant samples.Conclusion CTCs play an ancillary role in the diagnosis of pulmonary nodules.TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.

Potential utility of liquid biopsies in the management of patients with biliary tract cancers:A review

Biliary tract cancer,comprising gallbladder cancer,cholangiocarcinoma and ampullary cancer,represents a more uncommon entity outside high-endemic areas,though global incidence is rising.The majority of patients present at a late stage,and 5-year survival remains poor.Advanced stage disease is incurable,and though palliative chemotherapy has been shown to improve survival,further diagnostic and therapeutic options are required in order to improve patient outcomes.Although certain subtypes of biliary tract cancer are relatively rich in targetable mutations,attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient fitness.Liquid biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic,predictive and prognostic biomarkers.In this review,the current standard of care for patients with biliary tract cancer,future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be discussed.Circulating tumour DNA,circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer.A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.