TATA-box-binding protein-associated factor 15 is a novel biomarker that promotes cell proliferation and migration in gastrointestinal stromal tumor

BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.Thus,TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.

Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis:a cross-sectional study

Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.

CD93 serves as a potential biomarker of gastric cancer and correlates with the tumor microenvironment

BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.

Fecal microbial biomarkers combined with multi-target stool DNA test improve diagnostic accuracy for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition and multi-target stool DNA(MT-sDNA)test in the diagnosis of CRC.METHODS We assessed the performance of the MT-sDNA test based on a hospital clinical trial.The intestinal microbiota was tested using 16S rRNA gene sequencing.This case-control study enrolled 54 CRC patients and 51 healthy controls.We identified biomarkers of bacterial structure,analyzed the relationship between different tumor markers and the relative abundance of related flora components,and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size,redundancy analysis,and random forest analysis.RESULTS MT-sDNA was associated with Bacteroides.MT-sDNA and carcinoembryonic antigen(CEA)were positively correlated with the existence of Parabacteroides,and alpha-fetoprotein(AFP)was positively associated with Faecalibacterium and Megamonas.In the random forest model,the existence of Streptococcus,Escherichia,Chitinophaga,Parasutterella,Lachnospira,and Romboutsia can distinguish CRC from health controls.The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%,with a sensitivity and specificity of 98.1%and 92.3%,respectively.CONCLUSION There is a positive correlation of MT-sDNA,CEA,and AFP with intestinal microbiome.Eight biomarkers including six genera of gut microbiota,MT-sDNA,and CEA showed a prominent sensitivity and specificity for CRC prediction,which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.

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.

Predictive values of multidetector-row computed tomography combined with serum tumor biomarkers in preoperative lymph node metastasis of gastric cancer

Objective: Multidetector-row computed tomography(MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer(GC). This study intends to evaluate the clinical predictive value of MDCT and serum tumor biomarkers in lymph node metastasis of GC.Methods: The clinicopathologic data of 445 GC patients who underwent radical gastrectomy were retrospectively analyzed to evaluate the diagnostic value of MDCT and serum tumor biomarkers in lymph node metastatic staging of GC before surgery.Results: With the multinomial logistic regression analysis, the independent relative factors of lymph node metastasis of GC were identified as tumor size, depth of tumor invasion, vessel invasion, vascular embolus, and soft tissue invasion. The optimal critical value of the short diameter of lymph nodes detected by MDCT scanning for evaluation of preoperative lymph node metastasis was 6.0 mm, with 75.7% as predictive accuracy of lymph node metastasis compared to the postoperative pathological results of GC patients. In addition, the critical value of the short diameter of lymph nodes combined with serum tumor biomarkers [including carbohydrate antigen(CA)-724 and CA-199] could show an enhancement of predictive sensitivity of lymph node metastasis(up to 89.3%) before surgery.Conclusions: MDCT combined with serum tumor biomarkers should be adopted to improve preoperative sensitivity and accuracy of lymph node metastasis for GC patients.

Pancreatic neuroendocrine tumors:A review of serum biomarkers,staging,and management

Pancreatic neuroendocrine tumors(pNETs)are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading,clinical staging,and presence of symptoms related to hormonal secretion.With regard to diagnosis,remarkable advances have been made:Chromogranin A is recommended as a general marker for pNETs.But other new biomarker modalities,like circulating tumor cells,multiple transcript analysis,microRNA profile,and cytokines,should be clarified in future investigations before clinical application.Therefore,the currently available serum biomarkers are insufficient for diagnosis,but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs.Surgical resection is still the only curative therapeutic option for localized pNETs.However,a debulking operation has also been proven to be effective for controlling the disease.As for drug therapy,steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor,while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs.Great progress has been achieved in the combination of systematic therapy with local control treatments.The optimal timing of local control intervention,planning of sequential therapies,and implementation of multidisciplinary care remain pending.

Identification of lncRNAs associated with T cells as potentialbiomarkers and therapeutic targets in lung adenocarcinoma

Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select moretargeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. Thenumber, type, and function of T cells in the tumor microenvironment (TME) determine the progression andtreatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development,and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigatewhether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified tofurther establish the T cell-related lncRNA risk score (TRS) in LUAD. Low TRS individuals were characterized byrobust immune status, fewer genomic alterations, and remarkably longer survival than high TRS individuals. Theexcellent accuracy of TRS in predicting overall survival (OS) was validated in the TCGA-LUAD training cohort andthe GEO-LUAD validation cohort. Our data demonstrated the favorable predictive power of the TRS-basednomogram, which had important clinical significance in estimating the survival probability for individuals. Inaddition, individuals with low TRS could respond better to chemotherapy and immunotherapy than those with highTRS. LINC00525 was identified as a valuable study target, and the ability of LUAD to proliferate or invade wassignificantly attenuated by downregulation of LINC00525. In conclusion, the TRS established by T cell-Lncs couldunambiguously classify LUAD patients, predict their prognosis and guide their management. Moreover, our identifiedT cell-Lncs could provide potential therapeutic targets for LUAD.

A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer

Objective:DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer.This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4gene (PTGER4) DNA methylation in plasma,appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers.Methods:We developed a multimodal prediction model with a training set of 257 individuals.The performance of the multimodal prediction model was further validated in an independent validation set of 42 subjects.In addition,we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) portal.Results:There were significant differences between the early-stage lung cancers and benign groups in the methylation levels.The area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules,mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693,0.497 and 0.864,respectively,while the AUCs of PTGER4 were 0.559,0.739 and 0.619,respectively.With the highest AUC of0.894,the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation set.Database analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 mutations.Conclusions:The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs.A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

A pan-cancer analysis identifies SOAT1 as an immunological and prognostic biomarker

Sterol o-acyltransferase1(SOAT1)is an enzyme that regulates lipid metabolism.Nevertheless,the predictive value of SOAT1 regarding immune responses in cancer is not fully understood.Herein,we aimed to expound the predictive value and the potential biological functions of SOAT1 in pan-cancer.Raw data related to SOAT1 expression in 33 different types of cancer were acquired from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.SOAT1 expression was significantly increased in most cancers and showed a distinct correlation with prognosis.This enhanced expression of the SOAT1 gene was confirmed by evaluating SOAT1 protein expression using tissue microarrays.In addition,we found significant positive associations between SOAT1 expression levels and infiltrating immune cells,including T cells,neutrophils,and macrophages.Moreover,the co-expression analysis between SOAT1 and immune genes showed that many immune-related genes were increased with enhanced SOAT1 expression.A gene set enrichment analysis(GSEA)revealed that the expression of SOAT1 correlated with the tumor microenvironment,adaptive immune response,interferon signaling,and cytokine signaling.These findings indicate that SOAT1 is a potential candidate marker for predicting prognosis and a promising target for tumor immunotherapy in cancers.

Investigation of Combining Serum Tumor Biomarkers and Clinical Features for Elderly Lung Cancer Diagnosis and Classification

To evaluate the diagnosis model of serum tumor biomarker and several clinical features diagnose and classification for lung cancer, the solid protein chip technology (C-12) was used to detect the biomarkers of SF, CEA, CA242, NSE, CA125, CA19-9 and CA15-3 in serum and several clinical features of tumors and benign disease in elderly lung cancer patients were collected. Set up a discriminating analysis as a function diagnostic model in clinical elderly lung cancer diagnosis and sub-type discrimination. In combination of 2 obvious clinical indicators and 2 serum markers, it is possible to provide a diagnosis tool for lung cancer. With the help of mathematic model, it is promising to reduce the misjudgment risk based on the previous experience and therefore establish a reliable diagnosing function. This model is simple, cost-effective and easy to adapt in practice, and can also be used in screening of large population.

Integrated analysis of gene expression profiles reveals prognostic biomarkers for immunotherapy in cancer

Tumor immunotherapy has emerged as a promising method in cancer treatment,but patient responses vary,necessitating personalized strategies and prognostic biomarkers.This study aimed to identify prognostic factors and construct a predictive model for patient survival outcomes and immunotherapy response.We curated six immunotherapy datasets representing diverse cancer types and treatment regimens.After data preprocessing,patients were stratified based on immunotherapy response.Differential gene expression analysis identified 22 genes consistently dysregulated across multiple datasets.Functional analysis provided critical insights,highlighting the enrichment of these dysregulated genes in immune response pathways and tumor microenvironment-related processes.To create a robust prognostic model,we meticulously employed a multistep approach.Initially,the identified 22 genes underwent rigorous univariate Cox regression analysis to evaluate their individual associations with patient survival outcomes.Genes showing statistical significance(p-values<0.05)at this stage advanced to the subsequent multivariate Cox regression analysis,which aimed to address potential confounding factors and collinearity among genes.From this analysis,we ultimately identified four key genes—ST6GALNAC2,SNORA65,MFAP2,and CDKN2B—that were significantly associated with patient survival outcomes.Incorporating these four key genes along with their corresponding coefficients,we constructed a predictive model.This model’s efficacy was validated through extensive Cox regression analyses,demonstrating its robustness in predicting patient survival outcomes.Furthermore,our model exhibited promising predictive capability for immunotherapy response,providing a potential tool for anticipating treatment efficacy.These findings provide insights into immunotherapy response mechanisms and suggest potential prognostic biomarkers for personalized treatment.Our study contributes to advancing cancer immunotherapy and personalized medicine.

Single-cell analysis of tumors:Creating new value for molecular biomarker discovery of cancer stem cells and tumor-infiltrating immune cells

Biomarker-driven individualized treatment in oncology has made tremendous progress through technological developments, new therapeutic modalities and a deeper understanding of the molecular biology for tumors, cancer stem cells and tumor-infiltrating immune cells. Recent technical developments have led to the establishment of a variety of cancer-related diagnostic, prognostic and predictive biomarkers. In this regard, different modern OMICs approaches were assessed in order to categorize and classify prognostically different forms of neoplasia. Despite those technical advancements, the extent of molecular heterogeneity at the individual cell level in human tumors remains largely uncharacterized. Each tumor consists of a mixture of heterogeneous cell types. Therefore, it is important to quantify the dynamic cellular variations in order to predict clinical parameters, such as a response to treatment and or potential for disease recurrence. Recently, single-cell based methods have been developed to characterize the heterogeneity in seemingly homogenous cancer cell populations prior to and during treatment. In this review, we highlight the recent advances for single-cell analysis and discuss the challenges and prospects for molecular characterization of cancer cells, cancer stem cells and tumor-infiltrating immune cells.

Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

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.

miR-153 as biomarker for cancer-functional role as tumor suppressor

MicroRNA-153(miR-153),belongs toa dass of small non-coding RNA.It is a aritical regulator of gene expression at the post-transcriptional lewel which interacts with the functional mRNA at 3UTR rgion and suppresses the expression of the mRNA.More recently,it has become apparent that dhanges in the miR-153 axpression lead to invasion,metastasis,angiogenesis and various types of tumor progression.This review summarizes the connection between dysrgulation of miR-153 and various typas of cancer progression.miR-153 regulates various signaling pathways to inhibit the proliferation and induce apoptosis in the ancer cell and also show synergistic activity with anticancer drugs.In addition to this,the oncogenic bchavior of miR-153 and their use as a potential biomarker in cancer was also reviewed.

Biomarkers in colorectal cancer: Current clinical utility and future perspectives

Colorectal cancer(CRC) is a major cause of cancer death worldwide. CRC has poor prognosis and there is a crucial need for new diagnostic and prognostic biomarkers to avoid CRC-related deaths. CRC can be considered a sporadic disease in most cases(75%-80%), but it has been suggested that crosstalk between gene mutations(i.e., mutations of BRAF, KRAS, and p53 as well as microsatellite instability) and epigenetic alterations(i.e., DNA methylation of Cp G island promoter regions) could play a pivotal role in cancer development. A number of studies have focused on molecular testing to guide targeted and conventional treatments for patients with CRC, sometimes with contrasting results. Some of the most useful innovations in the management of CRC include the possibility to detect the absence of KRAS, BRAF, NRAS and PIK3 CA gene mutations with the subsequent choice to administer targeted adjuvant therapy with anti-epidermal growth factor receptor antibodies. Moreover, CRC patients can benefit from tests for microsatellite instability and for the detection of loss of heterozygosity of chromosome 18 q that can be helpful in guiding therapeutic decisions as regards the administration of 5-FU. The aim of this review was to summarize the most recent evidence on the possible use of genetic or epigenetic biomarkers for diagnosis, prognosis and response to therapy in CRC patients.

Multiparametric MRI biomarkers for measuring vascular disrupting effect on cancer

Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis;a process known as tumor angiogenesis.Angiogenesis is largely involved in tumor survival,progression and spread,which are known to be significantly attributed to treatment failures.Over the past decades,efforts have been made to understand the difference between nor-mal and tumor vessels.It has been demonstrated that tumor vasculature is structurally immature with chaotic and leaky phenotypes,which provides opportunities for developing novel anticancer strategies.Targeting tumor vasculature is not only a unique therapeutic interven-tion to starve neoplastic cells,but also enhances the efficacy of conventional cancer treatments.Vascular dis-rupting agents(VDAs) have been developed to disrupt the already existing neovasculature in actively growing tumors,cause catastrophic vascular shutdown within short time,and induce secondary tumor necrosis.VDAs are cytostatic;they can only inhibit tumor growth,but not eradicate the tumor.This novel drug mechanism has urged us to develop multiparametric imaging biomark-ers to monitor early hemodynamic alterations,cellular dysfunctions and metabolic impairments before tumor dimensional changes can be detected.In this article,we review the characteristics of tumor vessels,tubulin-destabilizing mechanisms of VDAs,and in vivo effects of the VDAs that have been mostly studied in preclinical studies and clinical trials.We also compare the differ-ent tumor models adopted in the preclinical studies on VDAs.Multiparametric imaging biomarkers,mainly diffu-sion-weighted imaging and dynamic contrast-enhanced imaging from magnetic resonance imaging,are evalu-ated for their potential as morphological and functional imaging biomarkers for monitoring therapeutic effects of VDAs.

Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

In resectable colorectal liver metastasis(CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases(both resectable and non-resectable) and the shift in indication from "what is taken out"(e.g., how much liver has to be resected) to "what is left behind"(that is, how much functional liver tissue the patient has after resection). The latter is amenable to modifications by using adjunct techniques of portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications for cancer care.