Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts

BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.

Hyperhomocysteinemia and Associated Biological Markers in a Congolese Population of Type 2 Diabetes Mellitus in Brazzaville

The search for new biomarkers predictive of type 2 diabetes currently constitutes a research avenue in Bioclinical. Total homocysteine remains a preferred target due to its involvement in the occurrence of degenerative complications in type 2 diabetics. The aim of this work was to study hyperhomocysteinemia and other biochemical markers associated with T2D in the Congolese population. This was an analytical case-control study carried out between October 2022 and October 2023. The study population consisted of 150 subjects including 100 T2D patients and 50 control subjects. The main clinical data were collected on a pre-established form. Homocysteine determination was carried out by the sandwich ELISA method. The other biochemical markers were measured by colorimetric enzymatic methods. Hyperhomocysteinemia was present in 27.3% (41/150) of the entire study population. Type 2 diabetics had a frequency of hyperhomocysteinemia of 36% (36/100) and control 10% (5/50) (p = 0.001). The mean hyperhomocysteinemia concentration was 31.9 μmol/l with extremes ranging from 18 to 103 μmol/l. Means of biological markers between diabetics and controls showed a statistically significant difference (p = 0.01). The risk factors associated with this HHcy were: sex (OR = 3.5), age (OR = 9.4), sedentary lifestyle (OR = 3.4) and glycosylated hemoglobin (OR = 12) with a p-value <0.05 respectively. Our results suggest that hyperhomocysteinemia can be considered as a predictive biomarker in the bioclinic of Congolese type 2 diabetic patients.

Brain Urea as a Potential Biomarker of Neoplasm Progression

Metabolic reprogramming is a key feature driving oncogenesis in cancers. Recent studies have revealed that protein metabolism is largely altered in gliomas facilitating its malignant growth. Urea is the end product of nitrogen metabolism which is mainly produced by arginase. The interdependence of arginase and other biochemical mechanisms triggered scientific research interest. This research aimed to investigate the relationships between the urea as the main parameter of protein metabolism and glioma progression. It was also the most pronounced relationship between urea and the level of the nuclear protein Ki-67 as a marker of proliferative activity and O-6-methylguanine-DNA methyltransferase (MGMT), which performs DNA repair. Postoperative material from 20 patients with gliomas of different grades of anaplasia was analyzed.

Genome-Wide Analysis for Yield-Related Agronomic and Biochemical Traits of Chinese and Bangladeshi Grass Pea Genotypes Using SSR Markers

Grass pea(Lathyrus sativus L.)is an imperative food crop cultured in dryland agricultural ecology.It is a vital source of dietary protein to millions of populaces living in low-income countries in South-East Asia and Africa.This study highlights the improvement of genomic properties and their application in marker-trait relationships for 17 yield-related characters in 400 grass pea genotypes from China and Bangladesh.These characters were assessed via 56 polymorphic markers using general linear model(GLM)(P+G+Q)and mixed linear model(MLM)(P+G+Q+K)in the tassel software based on the linkage disequilibrium and population structure analysis.Population structure analysis showed two major groups and one admixed group in the populace.Statistically significant loci pairs of linkage disequilibrium(LD)mean value(D′)was 0.479.A total of 99 and 61 marker-trait associations in GLM and MLM models allied to the 17 traits were accepted at a 5%level of significance.Among these markers,21 markers were associated with more than one trait;12 marker-trait associations passed the Bonferroni correction threshold.Both models found six markers C41936,C39067,C34100,C47146,C47638,and C43047 significantly associated with days to maturity,flower color,plant height,and seed per pod were detected in the Hebei and Liaoyang location(p≤0.01),and the interpretation rate(R^(2)value)11.2%to 43.6%.Conferring to the consequences,the association analysis methodology may operative system for quantitative,qualitative,and biochemical traits related to gene position mapping and support breeders in improving novel approaches for advancing the grass pea quality.

Review of the potential value of serum interleukin levels as prognostic biomarkers of liver failure

Liver failure(LF)is prevalent in China and is characterized by complex path-ogenesis,challenging clinical management,poor prognosis,and rising incidence and mortality rates.The immune status is an important factor affecting LF prognosis.Interleukins(Ils)are a type of cytokine that act and interact with multiple cells,including immune cells.These signaling molecules play important roles in intercellular information transmission,including the regulation of immune cells;mediation of the activation,proliferation,and differentiation of T and B cells;and orchestration of the inflammatory response.To date,many studies have explored the correlation between IL expression and liver disease prognosis,but few studies have evaluated Ils as the prognostic biomarkers of LF.This article reviews the potential use of Ils as the prognostic biomarkers of LF.Particularly,it evaluates the predictive values of IL-21,IL-22,and IL-31,the three often overlooked yet promising prognostic biomarkers,in predicting suscept-ibility to LF.Harnessing biomarkers for early prognostic insights can facilitate tailored treatment strategies and enhance patient survival.Thus,this article focuses on the identification of IL-21,IL-22,and IL-33 as biomarkers in preclinical and clinical studies on LF and reviews their role as biomarkers in the pathogenesis and diagnosis of LF.

Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers

BACKGROUND Portal vein thrombosis(PVT),a complication of liver cirrhosis,is a major public health concern.PVT prediction is the most effective method for PVT diagnosis and treatment.AIM To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis.METHODS Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved.Following a 1:1 propensity score matching 572 patients with cirrhosis were screened,and relevant clinical data were collected.PVT risk factors were identified using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression analysis.Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables.A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT,and its predictive performance was verified using a receiver operating characteristic curve(ROC),calibration curves,and decision curve analysis(DCA).Finally,a network calculator was constructed based on the nomograms.RESULTS This study enrolled 286 cirrhosis patients with PVT and 286 without PVT.LASSO analysis revealed 13 variables as strongly associated with PVT occurrence.Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors,including etiology,ascites,gastroesophageal varices,platelet count,D-dimer,portal vein diameter,portal vein velocity,aspartate transaminase to neutrophil ratio index,and platelet-to-lymphocyte ratio.LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables.A nomogram was constructed based on the screened independent risk factors.The nomogram had excellent predictive performance,with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups,respectively.Calibration curves and DCA revealed its good clinical performance.Finally,the optimal cutoff value for the total nomogram score was 0.513.The sensitivity and specificity of the optimal cutoff values were 0.822 and 0.706,respectively.CONCLUSION A nomogram for predicting PVT occurrence was successfully developed and validated,and a network calculator was constructed.This can enable clinicians to rapidly and easily identify high PVT risk groups.

Neutrophil gelatinase-associated lipocalin,kidney injury molecule-1,and periostin:Novel urinary biomarkers in diabetic nephropathy

BACKGROUND Globally,diabetic nephropathy(DN)is the primary cause of chronic kidney disease.Currently,renal function is monitored indirectly using measures of serum creatinine,estimated glomerular filtration rate(eGFR),and proteinuria.Novel urinary biomarkers utilized in the early stages of DN have been described;these indicators can be used in the early identification of the disease,which is important for initiating treatment to halt or impediment the advance of diabetic nephropathy.AIM To estimate neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and periostin(POSTN)levels as novel urinary biomarkers in DN.METHODS In this hospital based cross-sectional study,a total of 160 patients of both genders aged 18 years or more;40 healthy participants and 120 patients with diabetes mellitus(DM)were included.Patients with DM were divided into normoalbuminuria(n=40),microalbuminuria(n=40),and macroalbuminuria(n=40)groups as per urine albumin creatinine ratio(uACR).Blood urea,serum creatinine,uACR were measured.Urine NGAL,KIM-1,and POSTN were measured by enzyme linked immunosorbent assay.The eGFR was calculated and compared with urinary markers.RESULTS NGAL,KIM-1,and POSTN levels increased significantly in normo,micro,and macroalbuminuria with the highest in the macroalbuminuria group.Albumin creatinine ratio(ACR)showed a positive correlation with NGAL,KIM-1,and POSTN levels.The eGFR showed a weak negative correlation with ACR,NGAL,KIM-1,and POSTN.NGAL was significantly lower in stage 1 compared to stage 2,3,and 4 kidney disease.KIM-1 was significantly decreased in stage 1 compared to stage 4 kidney disease.POSTN was significantly decreased in stage 1 compared to stage 3 and 4 kidney disease.The receiver operator curve analysis of ACR,NGAL,KIM-1,and POSTN showed good sensitivity of 80%,75.8%,63.3%,and 80%respectively with a cut-off of 12.5 mg/g,4.5μg/L,1.5 ng/mL,and 37.5 ng/mL.CONCLUSION Urinary NGAL and POSTN are independent markers of DN.

Magnetic Resonance Imaging and Biological Markers in Pituitary Adenomas with Invasion of the Cavernous Sinus Space

Objective: To investigate the predictability of MRI and the possiblebiological markers of cavernous sinus invasion of pituitary adenomas associated with fourphenomenas: angiogenesis, cell proliferation, apoptosis and matrix metalloproteinase. Methods: Weevaluated 45 patients with pituitary adenoma according to the MRI, surgical findings and theimmunohistochemistry staining of tumor tissues. Results: The results have shown that the sensitivityof MRI for predicting cavernous sinus invasion in this prospective study was 60%, its specificity85%, its positive predictive value 83.33%, negative predictive value 62.96%. 45 specimens ofpituitary adenomas were analyzed for expression of F8, VEGF, Ki-67, c-myc, Bcl-2, nm23 and MMP-9immunoreactivity using immunoperoxidase staining. MVD was assessed using F8-related antigen. Theresults have shown that MVD of invasive pituitary adenomas was significantly higher than that ofnoninvasive (P 【 0.001). There was an association between the invasion of pituitary adenomas andKi-67 LI (P = 0.039) or the expression of VEGF (P 【 0.001) and MMP-9 (P 【 0.001). But c-myc LI andBcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 versus P =0.201). On the other hand, there is an inverse relationship between nm23 expression and tumorinvasion (P 【 0.001). Conclusion: Parasellar extension of pituitary adenomas through the medial wallof the cavernous sinus is diagnosed at surgery, and with sensitive gadolinium-enhanced MRI, itsextent can be partly determined by radiology. Although our study has shown that MVD and theexpression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas,they are lack of specificity. These markers can only provide some useful information.

牛膝化学成分和药理作用研究进展及其质量标志物(Q-Marker)预测分析

牛膝在《神农本草经》中被列为上品,近几年研究证实牛膝的化学成分主要包括甾体、三萜皂苷、多糖、挥发油等化合物,具有抗炎镇痛、调节免疫、抗骨质疏松、保护心血管等药效。本文从牛膝的植物亲缘性,牛膝特有性、有效性、可测性化学成分和炮制后化学成分等方面,对牛膝的质量标志物(quality marker,Q-Marker)进行预测分析,牛膝甾酮A、25 S-牛膝甾酮、25 R-牛膝甾酮、齐墩果酸-3-O-β-D-(6′-丁酯)-吡喃葡萄糖醛酸苷、齐墩果酸-3-O-β-D-(6′-甲酯)-吡喃葡萄糖醛酸苷、β-蜕皮甾酮等可作为牛膝质量标志物,为建立牛膝质量评价体系和深入研究其药理作用提供依据。

Biomarkers of gastric cancer:Current topics and future perspective

Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.

Sharpie marker在试管上标记对荧光PCR检测Ct值的影响

为了探明Sharpie marker在试管上标记对荧光PCR检测Ct值的影响,本试验模拟现实工作中可能遇到的各类情形,从Sharpie marker标记试管的各种方式,以对照组、全黑管、管壁全黑管、管壁和盖半黑管、管壁半黑管、盖半黑管和盖全黑管等为对象,通过荧光PCR检测,比较分析Ct值。结果显示,全黑管和盖全黑管对Ct值的影响最大,管壁和盖半黑管与盖半黑管对Ct值的影响较大,而管壁全黑管和管壁半黑管对反应Ct值没有影响。本研究为正确使用Sharpie marker,确保荧光PCR检测结果的准确提供了参考。

New trends in molecular and cellular biomarker discovery for colorectal cancer

Colorectal cancer(CRC) is the third leading cause of cancer death worldwide, which is consequence of multistep tumorigenesis of several genetic and epigenetic events. Since CRC is mostly asymptomatic until it progresses to advanced stages, the early detection using effective screening approaches, selection of appropriate therapeutic strategies and efficient follow-up programs are essential to reduce CRC mortalities. Biomarker discovery for CRC based on the personalized genotype and clinical information could facilitate the classification of patients with certain types and stages of cancer to tailor preventive and therapeutic approaches. These cancer-related biomarkers should be highly sensitive and specific in a wide range of specimen(s)(including tumor tissues, patients' fluids or stool). Reliable biomarkers which enable the early detection of CRC, can improve early diagnosis, prognosis, treatment response prediction, and recurrence risk. Advances in our understanding of the natural history of CRC have led to the development of different CRC associated molecular and cellular biomarkers. This review highlights the new trends and approaches in CRC biomarker discovery, which could be potentially used for early diagnosis, development of new therapeutic approaches and follow-up of patients.

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.

Chronic hepatitis C virus infection:Serum biomarkers inpredicting liver damage

Currently, a major clinical challenge in the management of the increasing number of hepatitis C virus(HCV) infected patients is determining the best means for evaluating liver impairment. Prognosis and treatment of chronic hepatitis C(CHC) are partly dependent on the assessment of histological activity, namely cell necrosis and inflammation, and the degree of liver fibrosis. These parameters can be provided by liver biopsy; however, in addition to the risks related to an invasive procedure, liver biopsy has been associated with sampling error mostly due to suboptimal biopsy size. To avoid these pitfalls, several markers have been proposed as non-invasive alternatives for the diagnosis of liver damage. Distinct approaches among the currently available non-invasive methods are(1) the physical ones based on imaging techniques; and(2) the biological ones based on serum biomarkers. In this review, we discuss these approaches with special focus on currently available non-invasive serum markers. We will discuss:(1) class?Ⅰ?serum biomarkers individually and as combined panels, particularly those that mirror the metabolism of liver extracellular matrix turnover and/or fibrogenic cell changes;(2) class Ⅱ biomarkers that are indirect serum markers and are based on the evaluation of common functional alterations in the liver; and(3) biomarkers of liver cell death, since hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection. We highlight in this review the evidence behind the use of these markers and assess the diagnostic accuracy as well as advantages, limitations, and application in clinical practice of each test for predicting liver damage in CHC.

Neutral Red Retention by Earthworm Coelomocytes: A Biomarker of Cadmium Contamination in Soil

The earthworm Metaphire posthuma were used as a model to assess the toxic potential of cadmium incorporated into the soil by environmental or human activities. The retention period of neutral red in the lysosomes of the coelomocytes was used as a biomarker. The viability of harvested coelomocytes by a non_invasive extrusion protocol was 93% with no alteration by the dye during experimentation. The control cells retained dye for 119 and 121 min in normal soil and KCl, respectively, whereas a linear decline in the retention time in the treated earthworm coelomocytes was observed. This illustrated that the presence of cadmium caused damage to the lysosomes of the coelomocytes.

Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer

Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma(ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450 K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1,CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.

Perspectives on new biomarkers in gastric cancer: Diagnostic and prognostic applications

Gastric cancer is considered one of the most deadly tumors worldwide. Even with the decline in its incidence, the mortality rate of this disease has remained high, mainly due to its late diagnosis and to the lack of precise prognostic markers. The main purpose of this review is to present genetic, epigenetic and proteomic molecular markers that may be used in a diagnostic and prognostic manner and to discuss the pros and cons of each type of marker for improving clinical practice. In this sense, we observed that the use of genetic markers, especially mutations and polymorphisms, should be carefully considered, as they are strongly affected by ethnicity. Proteomic-based markers show promise, but the higher costs of the associated techniques con-tinue to make this approach expensive for routine use. Alternatively, epigenetic markers appear to be very promising, as they can be detected in bodily fluids as well as tissues. However, such markers must be used carefully because epigenetic changes may occur due to environmental factors and aging. Despite the advances in technology and its access, to date, there are few defined biomarkers of prognostic and diagnostic use for gastric tumors. Therefore, the use of a panel of several approaches(genetic, epigenetic and proteomic) should be considered the best alternative for clinical practice.

Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after LT.Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.

Diagnostic and therapeutic biomarkers in pancreaticobiliary malignancy

Pancreatic ductal adenocarcinoma(PDAC) and cholangiocarcinoma(CCA) are two malignancies that carry significant morbidity and mortality. The poor prognoses of these cancers are strongly related to lack of effective screening modalities as well as few therapeutic options. In this review, we highlight novel biomarkers that have the potential to be used as diagnostic, prognostic and predictive markers. The focus of this review is biomarkers that can be evaluated on endoscopically-obtained biopsies or brush specimens in the pre-operative setting. We also provide an overview of novel serum based markers in the early diagnosis of both PDAC and CCA. In pancreatic cancer, the emphasis is placed on prognostic and theranostic markers, whereas in CCA the utility of molecular markers in diagnosis and prognosis are highlighted.

Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

Sorafenib is the current standard treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However,efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2,hepatocyte growth factor,insulin-like growth factor-1,and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response,dynamic contrast-enhanced magnetic resonance imaging,and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC.