Circulating biomarkers in perioperative management of cancerpatients

Owing to the advances in surgical technology,most solid tumours can be controlled by surgical excision.The priority should be tumour control,while some routine perioperative management might influence cancer progression in an unnoticed way.Moreover,it is increasingly recognized that effective perioperative management should include techniques to improve postoperative outcomes.These influences are elucidated by the different functions of circulating biomarkers in cancer patients.Here,circulating biomarkers with two types of clinical functions were reviewed:(i)circulating biomarkers for cancer progression monitoring,for instance,those related to cancer cell malignancy,tumour microenvironment formation,and early metastasis,and(i)circulating biomarkers with relevance to postoperative outcomes,including systemic inflammation,immunosuppression,cognitive dysfunction,and pain management.This review aimed to provide new perspectives for the perioperative management of patients with cancer and highlight the potential clinical translation value of circulating biomarkers in improving outcomes.

Evolving utility of exosomes in pancreatic cancer management

Despite the development of newer oncological treatment,the survival of patients with pancreatic cancer(PC)remains poor.Recent studies have identified exosomes as essential mediators of intercellular communications and play a vital role in tumor initiation,metastasis and chemoresistance.Thus,the utility of liquid biopsies using exosomes in PC management can be used for early detection,diagnosis,monitoring as well as drug delivery vehicles for cancer therapy.This review summarizes the function,and clinical applications of exosomes in cancers as minimally invasive liquid biomarker in diagnostic,prognostic and therapeutic roles.

Novel insights regarding the role of noncoding RNAs in diabetes

Diabetes mellitus(DM)is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance,inadequate insulin secretion,or excessive glucagon secretion.In 2021,the global prevalence of diabetes is anticipated to be 10.7%(537 million people).Noncoding RNAs(ncRNAs)appear to have an important role in the initiation and progression of DM,according to a growing body of research.The two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding RNAs.miRNAs are singlestranded,short(17–25 nucleotides),ncRNAs that influence gene expression at the post-transcriptional level.Because DM has reached epidemic proportions worldwide,it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases efficiently.miRNAs are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression regulation.In this review,we address the issue of the gradually expanding global prevalence of DM by presenting a complete and upto-date synopsis of various regulatory miRNAs involved in these disorders.We hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for DM.We examine and synthesize recent research that used novel,high-throughput technologies to uncover ncRNAs involved in DM,necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses.

High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients

BACKGROUND Gastric cancer(GC)remains an aggressive malignancy with a high rate of mortality,being the third leading cause of cancer-related death.More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018.GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients.The discovery of new biomarkers useful in the early diagnosis of GC is mandatory.AIM To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.METHODS Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1.Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue.The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients.Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.RESULTS Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue(P<0.05).COL10A1 seems to show an elevated expression from the beginning of carcinogenesis,in the early stages,and its increased level remains elevated during cancer progression.A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified.Moreover,increased COL10A1 plasma level was associated with poor survival of the patients.Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve(AUC)of 0.9171(P=0.0002),sensitivity of 87.76%,and specificity of 100.0%.Furthermore,this study demonstrated the potential role of plasma COL10A1 in the early detection of GC,as in the early stage,we obtained an AUC of 0.8789(P=0.0030),sensitivity of 81.25%,and specificity of 100.0%.CONCLUSION Circulating expression level of COL10A1 is significantly increased in gastric adenocarcinoma patients being associated with poor survival and is a potential biomarker for early detection of GC.

Liquid biopsy in cholangiocarcinoma:Current status and future perspectives

Cholangiocarcinoma(CCA)are a heterogeneous group of tumors in terms of aetiology,natural history,morphological subtypes,molecular alterations and management,but all sharing complex diagnosis,management,and poor prognosis.Several mutated genes and epigenetic changes have been detected in CCA,with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets.Accessing tumoral components and genetic material is therefore crucial for the diagnosis,management and selection of targeted therapies;but sampling tumor tissue,when possible,is often risky and difficult to be repeated at different time points.Liquid biopsy(LB)represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples.Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated,allowing a real-time monitoring of the tumor genetic profile or the response to therapy.In this review,we analysis the current evidence on the possible roles of LB(circulating DNA,circulating RNA,exosomes,cytokines)in the diagnosis and management of patients affected by CCA.

Cell-free mitochondrial DNA quantification in ischemic stroke patients for non-invasive and real-time monitoring of disease status

BACKGROUND Acute ischemic stroke(AIS)is one of the major causes of the continuous increasing rate of global mortality due to the lack of timely diagnosis,prognosis,and management.This study provides a primitive platform for non-invasive and cost-effective diagnosis and prognosis of patients with AIS using circulating cellfree mitochondrial DNA(cf-mtDNA)quantification and validation.AIM To evaluate the role of cf-mtDNA as s non-invasive,and affordable tool for realtime monitoring and prognosticating AIS patients at disease onset and during treatment.METHODS This study enrolled 88 participants including 44 patients with AIS and 44 healthy controls with almost similar mean age group at stroke onset,and at 24 h and 72 h of treatment.Peripheral blood samples were collected from each study participant and plasma was separated using centrifugation.The cf-mtDNA concentration was quantified using nanodrop reading and validated through real-time quantitative polymerase chain reaction(RT-qPCR)of NADH-ubiquinone oxidoreductase chain 1(ND1)relative transcript expression levels.RESULTS Comparative analysis of cf-mtDNA concentration in patients at disease onset showed significantly increased levels compared to control individuals for both nanodrop reading,as well as ND1 relative expression levels(P<0.0001).Intergroup analysis of cf-mtDNA concentration using nanodrop showed significantly reduced levels in patients at 72 h of treatment compared to onset(P<0.01).However,RT-qPCR analysis showed a significant reduction at 24 h and 72 h of treatment compared to the disease onset(P<0.001).The sensitivity and specificity were relatively higher for RT-qPCR than nanodrop-based cfmtDNA quantification.Correlation analysis of both cf-mtDNA concentration as well as ND1 relative expression with National Institute of Health Stroke Scale score at baseline showed a positive trend.CONCLUSION In summary,quantitative estimation of highly pure cf-mtDNA provides a simple,highly sensitive and specific,non-invasive,and affordable approach for real-time monitoring and prognosticating AIS patients at onset and during treatment.

Detection of circulating tumor cells in blood of pancreatic ductal adenocarcinoma patients

Aim:Previous studies suggest that circulating tumor cells(CTC)are present at very low frequencies in blood of pancreatic cancer(PC)patients.However,no technique has proven efficient for their detection,in part due to the lack of accurate tumor markers.Here,we evaluated the potential utility of two marker candidates-Mucin 16(MUC16)and Tetraspanin 1(TSPAN1)-identified through a detailed review of the literature.Methods:To evaluate the pattern of expression of both markers in pancreatic tumor cells vs.normal blood,we used cell lines derived from pancreatic cancer patients and blood from healthy adults.Results:Antibodies against both MUC16 and TSPAN1 showed expression in three pancreatic cancer(PC)cell lines while they were absent in blood cells.To evaluate the efficiency of isolating tumor cells from blood,PC cell lines were spiked at different frequencies in blood,sequentially stained with biotin-conjugated TSPAN1 and MUC16 antibodies and a streptavidin ferrofluids,followed by immunomagnetic enrichment.The recovery of spiked TSPAN1+tumor cells was high with limited contamination by leukocytes.In contrast,no PC cells were isolated when the biotin MUC16 reagent was used because the biotin-conjugated clone did not recognize PC cells.Conclusion:The combination of MUC16,TSPAN1,and epithelial cell adhesion molecule(EpCAM)antibodies will likely increase the efficiency of capturing circulating tumor cell in blood of pancreatic ductal adenocarcinoma.To further develop a protocol for isolation of circulating tumor cell in blood of PC patients,high amounts of antibodies(5-10 mg)against EpCAM,MUC16,and TSPAN1 will be needed.

Liquid biopsies:DNA methylation analyses in circulating cell-free DNA

Analysis of patient＇s materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potential for numerous diagnostic applications. Circulating cell-free DNA（cfDNA） is explored as a prognostic or predictive marker of liquid biopsies with the improvements in genomic and molecular methods. DNA methylation is an important epigenetic marker known to affect gene expression. cfDNA methylation detection is a very promising approach as abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. This re？view summarizes the various investigational applications of cfDNA methylation and its oxidized de？rivatives as biomarkers for cancer diagnosis, prenatal diagnosis and organ transplantation monitoring.The review also provides a brief overview of the technologies for cfDNA methylation analysis based on next generation sequencing.

Liquid biopsies to predict CDK4/6 inhibitor efficacy and resistance in breast cancer

Cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors combined with endocrine therapy have transformed the treatment of estrogen receptor-positive(ER+)and human epidermal growth factor receptor 2 negative(HER2-)metastatic breast cancer.However,some patients do not respond to this treatment,and patients inevitably develop resistance,such that novel biomarkers are needed to predict primary resistance,monitor treatment response for acquired resistance,and personalize treatment strategies.Circumventing the spatial and temporal limitations of tissue biopsy,newly developed liquid biopsy approaches have the potential to uncover biomarkers that can predict CDK4/6 inhibitor efficacy and resistance in breast cancer patients through a simple blood test.Studies on circulating tumor DNA(ctDNA)-based liquid biopsy biomarkers of CDK4/6 inhibitor resistance have focused primarily on genomic alterations and have failed thus far to identify clear and clinically validated predictive biomarkers,but emerging epigenetic ctDNA methodologies hold promise for further discovery.The present review outlines recent advances and future directions in ctDNA-based biomarkers of CDK4/6 inhibitor treatment response.