Molecular Profiling of Sugarcane Wine, a Traditional Fermented Beverage (Loungouila) from Madingou

A number of studies reported that traditional fermented beverages possessed pharmaceutical biomolecules involved in biocatalysis for good therapeutic effects on various pathology including tumor, diabetes, inflammation, and obesity. This dimension of understanding is the prerogative of the biomolecular profile found in these fermented foods and beverages. The current work aimed to study the postfermentation molecular profile of the Congolese fermented beverage (Lougwila). The determination of pH, the acidity titratable, the distillation of sugar cane, the determination of total polyphenols and flavonoids and the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) have been used. As results, the fermenting sugar cane juice at room temperature for a period of seven days, leading to a decrease of the pH value to 4.25 ± 0.10 and increase in titratable acidity and alcohol content of at least 6.421 g/L (w/v) and 7% respectively. The polyphenol concentration of Loungouila increase from 14.9 to 20.5 mg Eq AG/g Ms after 10 days of fermentation. The flavonoid concentration varies from 1.70 to 5.22 mg Eq Cat/g Ms. among 46 isolates of Bacillus species, 55% (25/45) were able to show a very interesting clear zones in terms of cellulolytic activity with the percentage ranging from 37.3% to 83.9%, and 41.3% of amylolytic activity for the percentage ranging from 52.02% to 75%. 65.21% (30/46) of the isolates tested were found to be positive by the caseinolytic test with zones of inhibition ranging in diameter from 1.10 ± 0.09 to 3.25 ± 0.07 cm. In addition to the determination of biomolecule profile, 34.78% (16/46) of Bacillus isolates were able to produce biosurfactants with percentages ranging from 14% to 100%. Proteomic profiling of Loungouila has been investigated by using MALDI-TOF Technique. Short sequences showed 100% identity and were associated with AprE, SubC, amyE, NprE, CelA, lytF, Mut, and ykfC proteins. The National Center for Biotechnology Information (NCBI) allowed to associate short sequences to Bacillus species.

Pancreatic acinar cell carcinoma: A review on molecular profiling of patient tumors

Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC's molecular profiling showed a number of gene alterations such as: SMAD4,BRAF,BRCA2,TP53,RB1,MEN1,JAK-1,BRCA-1,BRCA-2,and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore,molecular profiling of PACC should be an option for patients with refractory PACC.

Clinical distribution and molecular profiling on postoperative colorectal cancer patients with different traditional Chinese medicine syndromes

Background:Traditional Chinese medicine(TCM)syndrome,also named syndrome,are comprehensive and integral analyses of clinical information which helps to guide different individualized treatment prescriptions.Methods:Thirty healthy controls and 80 colorectal cancer(CRC)patients(including 33 Spleen Qi Deficiency syndrome,23 Dampness Heat syndrome,17 Blood Stasis syndrome and 7 other syndrome)were enrolled into this study.Human mRNAs were extracted from peripheral blood mononuclear cells.The gene expression for CRC patients with different TCM syndrome was determined by microarray and qRT-PCR.Results:Spleen Qi Deficiency,Dampness Heat and Blood Stasis were the most common syndromes in CRC patients.There is a significant difference was found in mRNA expression levels(especially for PIK3CA,STAT3,SOX9 and KDM5C)among Spleen Qi Deficiency,Dampness Heat and Blood Stasis syndrome groups.The higher mRNA levels of JNK1,TP53,MLH1,MSH6,PMS2,SOCS3,TCF7L2,FAM123B,PSAP,FBXW7,SALL4 and the lower expression of inflammatory cytokine IL-6 were found in Spleen Qi Deficiency group but not other syndrome types.The higher mRNA levels of KRAS,MUC16,EGFR,GRASP65,PIK3CA,MAPK7,CD24,STAT3,SLC11A1,Bcl-2,TXNDC17 and some inflammatory cytokines(IL-6,IL-23,TNF-a,CXCR4)were found in Dampness Heat group but not other syndrome types.Blood Stasis syndrome showed higher expression of SOX9,MLH1,MSH6,KDM5C,PCDH11X,PSAP and SALL4,and lower mRNA levels of PIK3CA,CD24,STAT3,CXCR4,TXNDC17 and TP53.The CRC patients with Dampness Heat syndrome might have a poor prognosis than other syndrome types.Conclusion:The identification of syndrome conditions had different impacts on CRC prognosis,and which might be related with different mRNA expression levels.Some oncogenes and pro-inflammatory cytokines were highly expressed in Dampness Heat group but not other syndrome types,suggesting that the CRC patients with Dampness Heat syndrome might have a poor prognosis.Our results prelimitarily uncovered the molecular basis of syndrome differences in CRC prognosis,a better understanding for TCM treatment of CRC.

Molecular profiling of indolent human prostate cancer： tackling technical challenges to achieve high-fidelity genome-wide data

The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded （FFPE） tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.

New generation of breast cancer clinical trials implementing molecular profiling

The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as prescreening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i)longitudinal cohort studies that implement(or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.

Global Dynamic Molecular Profiling of Stomatal Lineage Cell Development by Single-Cell RNA Sequencing

The regulation of stomatal lineage cell development has been extensively investigated.However,a comprehensive characterization of this biological process based on single-cell transcriptome analysis has not yet been reported.In this study,we performed RNA sequencing on 12844 individual cells from the cotyledons of 5-day-old Arabidopsis seedlings.We identified 11 cell clusters corresponding mostly to cells at specific stomatal developmental stages using a series of marker genes.Comparative analysis of genes with the highest variable expression among these cell clusters revealed transcriptional networks that regulate development from meristemoid mother cells to guard mother cells.Examination of the developmental dynamics of marker genes via pseudo-time analysis revealed potential interactions between these genes.Collectively,our study opens the door for understanding how the identified novel marker genes participate in the regulation of stomatal lineage cell development.

Virological and Molecular Profile of People Living with the Human Immunodeficiency Virus Starting Dolutegravir Based Antiretroviral Treatment in Kinshasa, Democratic Republic of Congo

Context: Despite the new recommendations “Test and Treat”, the virological and molecular parameters remain important information for Antiretroviral Treatment and adequate for monitoring of patients infected with HIV/AIDS. Objective: the Objective of this study is to present the virological and molecular profile of People Living with HIV starting Antiretroviral Therapy in Kinshasa in the era of the Dolutegravir. Methods: This was a transversal study to determine virological and molecular profile of People Living with HIV (PLHIV) starting an ARV Treatment. The patient’s inclusion period was from October 04, 2021 to February 15, 2022. A sample of 5 ml of blood was taken in a tube with EDTA anticoagulant for Molecular Biology analyzes (Viral Load and Sequencing) in all HIV patients, after reading and signing informed consent. The population was made up of adult patients over the age of 18, infected with HIV and starting ART. Results: 119 patients (56.3% of women) were included in this study, thus a sex-ratio of 1.29. The average age of patients included was 39.87 ± 12.36 years. The most represented age group is that of 36 to 45 with 37 patients (31.9%) followed by that from 26 to 35 years with 24 patients (20.7%). Out of 119 patients, 21 patients had an undetectable Viral Load (VL). The median value of VL was 4.16 log10 RNA copies/ml. 114 samples were successfully amplified. Subtype A was dominant with 23 cases (20.2%);followed by the subtype C and CRF02_AG each with 14.0%, and D (10.5 %). K65R (1.8%), T69P/N (4.4%), K70R (7.9%) and M184V (7.0%) mutations were listed as existing mutations for Nucleotide Transcriptase Inhibitors. Conclusion: 38 patients (31.93%) started the TARV with a positive virological prognosis. The subtype A remains dominant in Kinshasa with 23 cases (20.2%);followed by the subtype C and CRF02_AG each with 14.0%. For Inhibitors of Transcriptase Reverse Nucleotide;K65R, T69P/N, K70E/R and M184V mutations were found in patients’ naive of ARV Treatment.

Agromorphological and Molecular Characterization of Sesamum indicum L.—An Oil Seed Crop

Sesamum indicum L. (family: Pedaliaceae) is an economically important oil seed crop grown in tropical and sub-tropical countries. It is widely used in food, nutraceutical, pharmaceutical industries. Sesamum is widely distributed in all the climatic stages and great diversity. The exploration of genetic diversity is a pre-requisite for genome organization in the landraces and the related domesticated ones. Agromorphological and molecular markers were used to assess the identification of 33 Sesamum genotypes and determination of the genetic relationships among these genotypes. Out of 30 Inter-Simple Sequence Repeat (ISSR) primers tested, 18 primers produced 114 detectable fragments, of which 97 (85.08%) were polymorphic across the varieties. Molecular profiling could be solely used for their identification of genotypes. Genetic relationships among these genotypes were evaluated by generating a similarity matrix based on the Jacard’s coefficient and the Unweighted Pair Group Method with Arithmetic Average (UPGMA) dendogram. The results showed a clear cut separation of the 33 genotypes and were in broad agreement with the morphology. Both molecular and morphological markers will be useful for preservation of the germplasm as well as breeding program.

Antimicrobial Resistance,Virulence Profile,and Molecular Characterization of Listeria monocytogenes Isolated from Ready-to-eat Food in China,2013-2014

We aimed to investigate the potential pathogenic profile and antibiotic resistance of Listeria monocytogenes isolated from ready-to-eat food in China.Antimicrobial resistance was determined by broth microdilution following the Clinical and Laboratory Standards Institute protocol Molecular serotyping,virulence,and resistance genes were identified using PCR.Multi-locus

Aptamer-Based Cell-Surface Profiling with Single-Cell Resolution Enables Precise Cancer Characterization

Molecular profiling of cell-surface proteins is a powerful strategy for precise cancer diagnosis.While mass cytometry(MC)enables synchronous detection of over 40 cellular parameters,its full potential in disease classification is challenged by the limited types of recognition probes currently available.In this work,we synthesize a panel of heavy isotopeconjugated aptamers to profile cancer-associated signatures on the surface of hematological malignancy(HM)cells.Based on 15 molecular signatures,we performed cell-surface profiling that allowed the precise classification of 8 HM cell lines.Combined with machine-learning technology,this aptamer-based MC platform also achieved multiclass identification of HM subtypes in clinical sampleswith 100%accuracy in the training cohort and 80%accuracy in the test cohort.Therefore,we report an effective and practical strategy for precise cancer classification at the singlecell level,paving the way for its clinical use in the near future.

Molecular pathology for cholangiocarcinoma:a review of actionable genetic targets and their relevance to adjuvant&neoadjuvant therapy,staging,follow-up,and determination of minimal residual disease

Cholangiocarcinoma(CCA)represents a group of epithelial cell tumors classified based on their anatomic location along the biliary tree.This rare malignancy is often diagnosed at an advanced stage and deemed unresectable.Even for those patients who are surgical candidates,recurrence rates are high and survival rates low.The mainstay of therapy for advanced CCA remains cisplatin plus gemcitabine,with a median overall survival(mOS)under 12 months,although the TOPAZ-1 trial showed a survival benefit with the addition of programmed cell death ligand 1(PD-L1)blockade.In recent years,molecular profiling has revealed a wealth of potentially targetable genetic alterations,including fibroblast growth factor receptor(FGFR)fusions,isocitrate dehydrogenase 1(IDH1)mutations,human epidermal growth factor receptor 2(HER2)amplification and overexpression,and microsatellite instability(MSI).These discoveries have prompted numerous clinical trials employing drugs against these specific genetic changes.The foundation laid by early clinical studies and the landscape of ongoing trials are both summarized here.While the role of adjuvant therapy has yet to be defined in this disease,we emphasize the importance of employing targeted therapies in trials in the adjuvant and neoadjuvant spaces and discuss ways to overcome challenges due to low incidence of targetable mutations.Personalized medicine for this disease promises significant clinical benefit to patients,but further investigation is needed.

Circulating tumor DNA:Where are we now?A mini review of the literature

For many years tissue biopsy has been the primary procedure to establish cancer diagnosis and determine further treatment and prognosis.However,this method has multiple drawbacks,including,to mention some,being an invasive procedure carrying significant risk for fragile patients and allowing only for a“snapshot”of the tumor biology in time.The process of liquid biopsy allows for a minimally invasive procedure that provides molecular information about underlying cancer by analyzing circulating tumor DNA(ctDNA)via next-generation sequencing technology and circulating tumor cells.This paper focuses on describing the basis of ctDNA and its current utilities.

Operable gastro-oesophageal junctional adenocarcinoma: Where to next?

Oesophageal junctional adenocarcinoma is a challeng-ing and increasingly common disease. Optimisation ofpre-operative staging and consolidation of surgery inlarge volume centres have improved outcomes, howev-er the preferred adjunctive treatment approach remainsa matter of debate. This review examines the benefitsof neoadjuvant, peri-operative, and post-operative che-motherapy and chemoradiotherapy in this setting in anattempt to reach an evidence based conclusion. Recentfindings relating to the molecular characterisation ofoesophagogastric cancer and their impact on therapeu-tics are explored, in addition to the potential benefitsof fluoro-deoxyglucose positron emission tomography(FDG-PET) directed therapy. Finally, efforts to decreasethe incidence of junctional adenocarcinoma using earlyintervention in Barrett's oesophagus are discussed,including the roles of screening, endoscopic mucosalresection, ablative therapies and chemoprevention.

Pancreatic head vs pancreatic body/tail cancer:Are they different?

BACKGROUND The impact of pancreatic tumor location on patient survival has been studied in large national data-based analyses which yielded controversial results.AIM To explore if pancreatic head cancer(PHC)and pancreatic body/tail cancer(PBTC)have different overall survival(OS),molecular signature and response to chemotherapy.METHODS We retrospectively queried patient records from July 2016 to June 2020 in our institution.Patient demographics,cancer stage on diagnosis,tumor location,somatic mutations,treatment,and survival are recorded and analyzed.A test is considered statistically significant if the P value was<0.05.RESULTS We reviewed 101 patients with complete records,among which 67(66.34%)were PHC and 34(33.66%)were PBTC.More PHC were diagnosed at younger age[61.49 vs 68.97,P=0.010],earlier stages(P=0.006)and underwent surgical resection(P=0.025).There were no significant differences among all mutations and pathways studied except for TP53 mutations(37.0%in PHC vs 70.0%in PBTC,P=0.03).OS was not statistically different between PHC and PBTC(P=0.636)in the overall population and in subgroups according to surgical resection status or stages.In terms of response to chemotherapy,chemotherapy regimens(FOLFIRINOX-based vs gemcitabine-based)didn’t impact disease free interval in those who had surgical resection in either PHC(P=0.546)or PBTC(P=0.654),or the duration of response to first line palliative treatment in those with advanced disease in PHC(P=0.915)or PBTC(P=0.524).CONCLUSION Even though PHC and PBTC have similar poor OS and response to chemotherapy,the different presentations and molecular profiles indicate they are different diseases.Utilization of molecular profiling to develop targeted therapy for individualization of treatment is needed.

Proteomic Portrait of Human Lymphoma Reveals Protein Molecular Fingerprint of Disease Specific Subtypes and Progression

An altered proteome in lymph nodes often suggests abnormal signaling pathways that may be associated with diverse lymphatic disorders.Current clinical biomarkers for histological classification of lymphomas have encountered many discrepancies,particularly for borderline cases.Therefore,we launched a comprehensive proteomic study aimed to establish a proteomic landscape of patients with various lymphatic disorders and identify proteomic variations associated with different disease subgroups.In this study,109 fresh-frozen lymph node tissues from patients with various lymphatic disorders(with a focus on Non-Hodgkin’s Lymphoma)were analyzed by data-independent acquisition mass spectrometry.A quantitative proteomic landscape was comprehensively characterized,leading to the identification of featured protein profiles for each subgroup.Potential correlations between clinical outcomes and expression profiles of signature proteins were also probed.Two representative signature proteins,phospholipid-binding proteins Annexin A6(ANXA6)and Phospholipase C Gamma 2(PLCG2),were successfully validated via immunohistochemistry.We also evaluated the capability of acquired proteomic signatures to segregate multiple lymphatic abnormalities and identified several core signature proteins,such as Sialic Acid Binding Ig Like Lectin 1(SIGLEC1)and GTPase of immunity-associated protein 5(GIMAP5).In summary,the established lympho-specific data resource provides a comprehensive map of protein expression in lymph nodes during multiple disease states,thus extending the existing human tissue proteome atlas.Our findings will be of great value in exploring protein expression and regulation underlying lymphatic malignancies,while also providing novel protein candidates to classify various lymphomas for more precise medical practice.

Liquid biopsy in ovarian cancer:Catching the silent killer before it strikes

Epithelial ovarian cancer(EOC)is the most lethal gynaecological malignancy in the western world.The majority of women presenting with the disease are asymptomatic and it has been dubbed the“silent killer”.To date there is no effective minimally invasive method of stratifying those with the disease or screening for the disease in the general population.Recent molecular and pathological discoveries,along with the advancement of scientific technology,means there is a real possibility of having disease-specific liquid biopsies available within the clinical environment in the near future.In this review we discuss these discoveries,particularly in relation to the most common and aggressive form of EOC,and their role in making this possibility a reality.

A search for evidence of small-scale inhomogeneities in dense cores from line profile analysis

In order to search for intensity fluctuations on the HCN（1-0） and HCO＋（1-0） line pro- files, which could arise due to possible small-scale inhomogeneous structure, long-term observations of high-mass star-forming cores S140 and S199 were carried out. The data were processed by the Fourier filtering method. Line temperature fluctuations that exceed the noise level were detected. Assuming the cores consist of a large number of randomly moving small thermal fragments, the total number of frag- ments is - 4 × 106 for the region with linear size - 0.1 pc in S140 and - 106 for the region with linear size - 0.3 pc in S 199. Physical parameters of fragments in S 140 were obtained from detailed modeling of the HCN emission in the framework of the clumpy cloud model.

Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection

The profile of T-cell receptor beta-chain variable （TRBV） genes usually skews in subjects with virus infection or cancer. The gene melting spectral pattern （GMSP） can be used to determine the profile of the TRBV gene family. To explore the portrait of the TRBV family in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection （AHI）, peripheral blood mononuclear cells （PBMCs） were separated and further sorted into CD4^＋ and CD8^＋ T-cell subsets. The molecular features of the TRBV complementary determining region 3 （CDR3） motifs were determined using GMSP analysis. When a GMSP profile showed a single peak, the monoclonally expanded TRBV gene was cloned and sequenced. Skewed expansions of multiple TRBV genes were observed among the CD4^＋ and CD8^＋ T-cell subsets and the PBMCs. The frequency of monoclonally expanded TRBV genes in the CD8^＋ T-cell subset was significantly higher than that of the CD4^＋ T-cell subset and the PBMCs. Compared to other members of the TRBV gene family, TRBV11, BV15 and BV20 were predominantly expressed in the repertoire of peripheral blood lymphocytes in recovered AHI subjects. The relatively conserved amino acid motifs of TRBV5.1 and BV20 CDR3 were also detected in the CD4^＋ and CD8^＋ T-cell subsets. These results demonstrate the presence of multiple biased TRBV families in recovered AHI subjects. TRBV11, BV15 and BV20, especially from the CD8＋ T-cell subset, may be relevant to the pathogenesis of subjects with AHh The preferentially selected TRBV5.1 and BV20 with the relatively conserved CDR3 motif may be potential targets for personalized treatments of chronic HBV infection.

Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor:A case report

BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs)are rare malignancies affecting the pancreas.The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components,each constituting 30%or more of the tumor volume.Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination.A well-differentiated neuroendocrine tumor(NET)component is rarely reported in MiNENs.CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas.The two tumors show distinct histology and significant differentiation discrepancy(poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET),and also present as metastases in separate lymph nodes.Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma,but no genetic alterations in the NET,suggesting divergent origins for these two components.Although tumors like this meet the diagnostic criteria for MiNEN,clinicians often find the diagnosis and staging confusing and impractical for clinical management.CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

The combined analysis of solid and liquid biopsies provides additional clinical information to improve patient care

Aim:To investigate if the genetic information provided by sequencing of both solid and liquid biopsies can shed light on tumor heterogeneity,and to understand the clinical usefulness of adding blood profiling to standard tissue analysis in cancer care.Methods:Data from 351 patients with stage IV solid tumors for whom molecular profiling of their solid and liquid biopsies was available were studied,with a focus on the discrepant molecular information found between tissue and blood samples.Results:In 86%of patients,solid and liquid biopsies provided different molecular information.Discrepant gene mutations with a functional impact on the corresponding protein were studied in detail.In 97%of cases,these additional mutations provided clinical value,mainly predicting sensitivity or resistance to targeted therapies.Specifically,42%of the mutations found only in the liquid biopsy were directly predictive of approved therapies(80%targeted therapies),while 54%were inclusion criteria for molecularly-matched trials.Conclusion:This study suggests that the addition of blood profiling should be considered in routine clinical oncology,especially for patients with metastatic disease where integrated analysis of solid and liquid biopsies provides a more complete characterization of tumor heterogeneity and provides valuable clinical information for patient treatment.