Landscape of urine biomarkers for bladder cancer:molecular function,cell-of-origin,and bibliometric trend

Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular functions and cell-of-origin profiles of these biomarkers are yet to be elucidated.In this study,we aimed to provide a comprehensive overview of the landscape of urinary biomarker genes for BCa.Methods:We conducted an exhaustive literature search in PubMed,through which 555 biomarker genes were identified.We then analyzed the BCa single-cell atlas to infer the cellular origin of these BCa urine biomarker genes and performed functional enrichment analysis to gain insights into the functional molecular implications of these biomarkers.Results:These genes are involved in tumor proliferation,angiogenesis,cellmigration,and cell death and are predominantly expressed in epithelial and stromal cells.Interestingly,our analysis ofmultiomics tumor data revealed a discordance between tissue and urine in terms of differential methylation and RNA expression,suggesting that biomarker discovery for liquid biopsies should ideally begin with the analysis of bodily fluids rather than relying interest and that test strategies incorporating multiple molecular markers represent an ongoing trend.Conclusions:Collectively,our study has built a landscape of BCa urine biomarker genes,uncovered molecular insights into these biomarkers,and revealed the bibliometric trends in this field,which will contribute to the discovery of novel biomarkers in the future.

Exploring the role of molecular biomarkers as a potential weapon against gastric cancer: a review of the literature

Gastric cancer(GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging Ⅱ-Ⅳ. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management.

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.

Molecular biomarkers for the detection of metastatic colorectal cancer cells

Approximately half of all patients with colorectal cancer develop local recurrence or distant metastasis during the course of their illness. Recently, the molecular detection of metastatic cancer cells in various types of clinical samples, such as lymph nodes, bone marrow, peripheral blood, and peritoneal lavage fluid, has been investigated as a potential prognostic marker. The prognostic value of molecular tumor cell detection was independent of the type of detection method used. As assays become more sensitive and quantitative, a more thorough assessment of the cancer status of patients will be based on molecular markers alone. At present, it is difficult to conclude that one specific molecular marker is superior to others. Comparative analyses are recommended to assess the prognostic impact of molecular analyses in the same patient and determine the biomarkers that provide the most accurate prognostic information.

NMI,POLR3G and APIP are the key molecules connecting glaucoma with high intraocular pressure:a clue for early diagnostic biomarker candidates

AIM:To understand the molecular connectivity between the intraocular pressure(IOP)and glaucoma which will provide possible clues for biomarker candidates.METHODS:The current study uncovers the important genes connecting IOP with the core functional modules of glaucoma.An integrated analysis was performed using glaucoma and IOP microarray datasets to screen for differentially expressed genes(DEGs)in both conditions.To the selected DEGs,the protein interaction network was constructed and dissected to determine the core functional clusters of glaucoma.For the clusters,the connectivity of IOP DEGs was determined.Further,enrichment analyses were performed to assess the functional annotation and potential pathways of the crucial clusters.RESULTS:The gene expression analysis of glaucoma and IOP with normal control showed that 408 DEGs(277 glaucoma and 131 IOP genes)were discovered from two GEO datasets.The 290 DEGs of glaucoma were extended to form a network containing 1495 proteins with 9462 edges.Using ClusterONE,the network was dissected to have 12 clusters.Among them,three clusters were linked with three IOP DEGs[N-Myc and STAT Interactor(NMI),POLR3G(RNA Polymerase Ⅲ Subunit G),and APAF1-interacting protein(APIP)].In the clusters,ontology analysis revealed that RNA processing and transport,p53 class mediators resulting in cell cycle arrest,cellular response to cytokine stimulus,regulation of phosphorylation,regulation of type Ⅰ interferon production,DNA deamination,and cellular response to hypoxia were significantly enriched to be implicated in the development of glaucoma.Finally,NMI,POLR3G,and APIP may have roles that were noticed altered in glaucoma and IOP conditions.CONCLUSION:Our findings could help to discover new potential biomarkers,elucidate the underlying pathophysiology,and identify new therapeutic targets for glaucoma.

Synergy between molecular biology and imaging science toward mechanism-based biomarkers associated with prostate cancer

Prostate cancer is a heterogeneous disease with subtypes that are characterized by different molecular profiles as a result of chromosomal rearrangements, epigenetic modifications, and activation of various signaling pathways. The subtype heterogeneity contributes to the challenges with a definitive diagnosis and biomarkers for disease progression. The current diagnostic test based on the detection of prostate specific antigen lacks sensitivity and specificity. Imaging plays an important role in characterizing biomarkers and elucidating the underlying molecular mechanisms. For example, 18F-fluoro-2-deoxy glucose is commonly used to assess cancer cell metabolism. More recently, magnetic resonance spectroscopic observations of the in vivo dynamic conversion of hyperpolarized 13C- pyruvate to lactate demonstrate that imaging enables the visualization of molecular processes. Biomarkers have also been developed that reveal aberrant cell growth and proliferation, both hallmarks of cancer. Androgen dependent and independent signaling path- ways underpin prostate cancer pathogenesis as they lead to downstream effect in cell growth, proliferation, survival, and suppression of apoptosis. Molecular imaging with radiolabeled ligands and positron emission tomography/computed tomography has provided quantitative characterization of the interactions between receptors and testosterone or growth factors. These observations, along with data on genetic alterations of the receptor genes, shed light on signal transduction involved in prostate cancer. This review article highlights advances in the understanding of the molecular mechanisms of prostate cancer and the synergy of this knowledge with imaging in characterizing potential biomarkers of the disease.

Molecular biomarkers for grass pollen immunotherapy

Grass pollen allergy represents a significant cause of allergic morbidity worldwide. Component-resolved diagnosis biomarkers are increasingly used in allergy practice in order to evaluate the sensitization to grass pollen allergens, allowing the clinician to confirm genuine sensitization to the corresponding allergen plant sources and supporting an accurate prescription of allergy immunotherapy(AIT), an important approach in many regions of the world with great plant biodiversity and/or where pollen seasons may overlap. The search for candidate predictive biomarkers for grass pollen immunotherapy(tolerogenic dendritic cells and regulatory T cells biomarkers, serum blocking antibodies biomarkers, especially functional ones, immune activation and immune tolerance soluble biomarkers and apoptosis biomarkers) opens new opportunities for the early detection of clinical responders for AIT, for the follow-up of these patients and for the development of new allergy vaccines.

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cellbased therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transforma-tion of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-Raf V600 E and N-RasQ 61 R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor(EGFR), stem cell-like factor(SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor-4(CXCR4) and vascular endothelial growth factor(VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition(EMT)-associated molecules, including phosphatidylinositol 3'-kinase(PI3K)/Akt/ molecular target of rapamycin(mT OR), nuclear factor-kappaB(NF-κB), macrophage inhibitory cytokine-1(MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.

Biomarkers for hepatocellular carcinoma: What's new on the horizon?

Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.

Novel biomarkers for patient stratification in colorectal cancer:A review of definitions,emerging concepts,and data

Colorectal cancer(CRC) treatment has become more personalised,incorporating a combination of the individual patient risk assessment,gene testing,and chemotherapy with surgery for optimal care.The improvement of staging with high-resolution imaging has allowed more selective treatments,optimising survival outcomes.The next step is to identify biomarkers that can inform clinicians of expected prognosis and offer the most beneficial treatment,while reducing unnecessary morbidity for the patient.The search for biomarkers in CRC has been of significant interest,with questions remaining on their impact and applicability.The study of biomarkers can be broadly divided into metabolic,molecular,micro RNA,epithelial-to-mesenchymal-transition(EMT),and imaging classes.Although numerous molecules have claimed to impact prognosis and treatment,their clinical application has been limited.Furthermore,routine testing of prognostic markers with no demonstrable influence on response to treatment is a questionable practice,as it increases cost and can adversely affect expectations of treatment.In this review we focus on recent developments and emerging biomarkers with potential utility for clinical translation in CRC.We examine and critically appraise novel imaging and molecular-based approaches; evaluate the promising array of micro RNAs,analyze metabolic profiles,and highlight key findings for biomarker potential in the EMT pathway.

Biomarkers in renal transplantation:An updated review

Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasiveindicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment. Biomarkers predicting or diagnosing acute rejection either cell-mediated or antibody-mediated allow a risk stratification of the recipient, a prompt diagnosis in an early phase when the histology is still unremarkable. The kidney solid organ response test detects renal transplant recipients at high risk for acute rejection with a very high sensitivity and is also able to make diagnosis of subclinical acute rejection. Other biomarkers are able to detect chronic allograft dysfunction in an early phase and to differentiate the true chronic rejection from other forms of chronic allograft nephropathies no immune related. Finally biomarkers recently discovered identify patients tolerant or almost tolerant. This fact allows to safely reduce or withdrawn the immunosuppressive therapy.

Alkane Biomarkers in Permian-Triassic Boundary Strata at Meishan Section, Changxing, Zhejiang Province

Meishan Section D in Changxing County, Zhejiang Province, China has been selected as the global stratotype of the Permian Triassic boundary and various studies have been done at the boundary, but the gas chromatographic mass spectrographic analysis of alkane biomarkers has not been investigated. This paper presents the results of a study of the biomarkers analyzed in a series of samples across the Permian Triassic boundary at both Meishan Section A and Section D. The results show that the overall concentration of alkane biomarkers in the Permian Triassic boundary strata is high in Bed 26 while it is low in Bed 27. A variety of biomarker parameters demonstrate that the main sources of organic matter in the sediment are algae and bacteria and that the depositional environment varied from weakly oxidizing to reducing during the studied interval.

Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer

Neoadjuvant therapy has been proven to be extremely valuable and is widely used for advanced esophageal cancer. However, a significant proportion of treated patients(60%-70%) does not respond well to neoadjuvant treatments and develop severe adverse effects. Therefore, predictive markers for individualization of multimodality treatments are urgently needed in esophageal cancer. Recently, molecular biomarkers that predict the response to neoadjuvant therapy have been explored in multimodal approaches in esophageal cancer and successful examples of biomarker identification have been reported. In this review, promising candidates for predictive molecular biomarkers developed by using multiple molecular approaches are reviewed. Moreover, treatment strategies based on the status of predicted biomarkers are discussed, while considering the international differences in the clinical background. However, in the absence of adequate treatment options related to the results of the biomarker test, the usefulness of these diagnostic tools is limited and new effective therapies for biomarker-identified nonresponders to cancer treatment should be concurrent with the progress of predictive technologies. Further improvement in the prognosis of esophageal cancer patients can be achieved through the introduction of novel therapeutic approaches in clinical practice.

Identification of candidate biomarkers correlated with pathogenesis of postoperative peritoneal adhesion by using microarray analysis

BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion are from complex biological processes.However,the molecular mechanisms underlying the basis of microarray data profile,followed by peritoneal adhesion formation,are largely unknown.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis.We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods.We performed quantitative PCR and western blotting in vivo to validate the results preliminarily.RESULTS In total,446 expressed genes were altered in peritoneal adhesion.We found that several hub genes(e.g.,tumor necrosis factor,interleukin 1 beta,interleukin 6,CX-C motif chemokine ligand 1,C-X-C motif chemokine ligand 2)were marked as significant biomarkers.Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway.According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies,TLR4,myeloid differentiation primary response protein 88(MyD88),and nuclear factor kappa B(NF-κB)played essential roles in Toll-like signaling transduction.Here,we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion.The results of the microarray analysis were verified by the animal experiments.These findings may extend our understanding of the molecular mechanisms of PPA.CONCLUSION The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA.Future studies are required to validate our findings.

Molecular Biomarker Characteristics of the Linxi Formation Source Rocks in the Middle-Western Region of Inner Mongolia:New evidence for late-stage tectonic evolution of the Paleo-Asian Ocean

Objective Two important geological issues have long been controversial in the Xing-Meng area of North China. The first concerns the final closure of Paleo-Asian Ocean in Xing-Meng area, and the other concerns the folding and lifting of the Xing-Meng Trough. The focus of thses issues is the Late Permian sedimentary environment, which is generally considered to be either an exclusively continental environment or from the closed inland sea environment in the Early to Middle stage to continental lacustrine environment in the late stage. In recent years, we have successively discovered abundant typical marine fossils （e.g., bryozoans and calcareous algae） in the Upper Permian thick limestone layer from Linxi County and Ar Horqin Banner in eastern region of Inner Mongolia and Jiutain County in Jilin Province. These significant findings have attracted the attention from fellow academics.

Updated overview of current biomarkers in head and neck carcinoma

Squamous cell cancer is the most common type of malignancy arising from the epithelial cells of the head and neck region. Head and neck squamous cell carcinoma(HNSCC) is one of the predominant causes of cancer related casualties worldwide. Overall prognosis in this disease has improved to some extent with the advancements in therapeutic modalities but detection of primary tumor at its initial stage and prevention of relapse are the major targets to be achieved for further improvement in terms of survival rate of patients. Latest achievements in basic research regarding molecular characterization of the disease has helped in better perception of the molecular mechanisms involved in HNSCC progression and also in recognizing and tar-geting various molecular biomarkers associated with HNSCC. In the present article, we review the infor-mation regarding latest and potential biomarkers for the early detection of HNSCC. A detailed molecular characterization, ultimately, is likely to improve the development of new therapeutic strategies, potentially relevant to diagnosis and prognosis of head and neck cancers. The need for more accurate and timely disease prediction has generated enormous research interests in this field.

Does the molecular classification of breast cancer point the way for biomarker identification in prostate cancer?

There is significant variation in clinical outcome between patients diagnosed with prostate cancer(Ca P). Although useful, statistical nomograms and risk stratification tools alone do not always accurately predict an individual's need for and response to treatment. The factors that determine this variation are not fully elucidated. In particular, cellular response to androgen ablation and subsequent paracrine/autocrine adaptation is poorly understood and despite best therapies, median survival in castrate resistant patients is only approximately 35 mo. We propose that one way of understanding this is to look for correlates in other comparable malignancies, such as breast cancer, where markers of at least 4 distinct gene clusters coding for 4 different phenotypic subtypes have been identified. These subtypes have been shown to demonstrate prognostic significance and successfully guide appropriate treatment regimens. In this paper we assess and review the evidence demonstrating parallels in the biology and treatment approach between breast and Ca P, and consider the feasibility of patients with Ca P being stratified into different molecular classes that could be used to complement prostate specific antigen and histological grading for clinical decision making. We show that there are significant correlations between the molecular classification of breast and Ca P and explain how techniques used successfully to predict response to treatment in breast cancer can be applied to the prostate. Molecular phenotyping is possible in Ca P and identification of distinct subtypes may allow personalised risk stratification way beyond that currently available.

海洋大气气溶胶中生物标志物研究进展

海洋气溶胶是海洋大气的重要组成部分,直接或间接影响地球系统的能量收支及气候变化。生物标志物如脂类、糖类、木质素类以及蛋白类化合物等,可用来识别海洋气溶胶的来源和提供重要的生物地球化学信息。然而,海洋气溶胶中单个有机物种的浓度很低,其检测和表征具有一定的挑战性。本文综述了海洋气溶胶中生物标志物的最新研究进展,包括检测方法、分子组成、来源和影响因素等。高分辨率色谱和质谱联用法广泛应用于海洋气溶胶中生物标志物测量,其他一些新兴的方法也被开发应用。海洋气溶胶中的脂类和糖类化合物的浓度呈现近岸高、远洋低的变化趋势,其浓度和组成随气象条件和排放源种类和强度变化呈现显著的季节特征,表明受到陆地长距离传输的影响。然而,更多研究强调了蛋白质和氨基酸的海洋生物来源,海洋排放的氨基酸在亚微米颗粒物上大量富集;蛋白质在长距离传输过程中由于光化学反应而降解。木质素也已被证明在远洋气溶胶中占比较高。此外,本文也指出了加强生物标志物在陆-海-气界面循环研究的必要性。

运动性疲劳的分子生物学机制及相关特异性基因靶点的研究进展

运动过程中肌肉的最大力量与功率输出、最快收缩速度与力量生成率以及肌肉耐力等特征是影响运动能力的关键因素。而肌肉力量的产生涉及从大脑皮层兴奋到运动单元激活,再到兴奋/收缩耦联等一系列生物级联反应,最终导致肌肉激活。包括内环境失衡与神经调节紊乱、氧化应激与炎症反应、能量代谢稳态调节与运动因子介导的肌肉—器官对话机制(crosstalk)诱发神经内分泌功能重塑过程中的功能障碍等都会影响肌肉力量的产生和维持,并可能最终诱发运动性疲劳(exercise-induced fatigue)。合理的运动训练方式和运动代谢调节及转录调控关键靶点的激活在促进运动适应性变化和预防运动性疲劳发生中起到重要保护作用。本文以运动诱发神经内分泌重塑、运动表观遗传调控关键靶点和运动疲劳相关特异性生物标记物为切入点,对运动性疲劳的分子机制及干预途径进行系统综述,以期为运动性疲劳的早期监测和合理干预提供新的研究思路和理论参考。

环状RNA调控卵巢癌及其化疗耐药的研究进展

卵巢癌是病死率最高的妇科恶性肿瘤,易产生化疗耐药而复发死亡,5年生存率仅为40%左右。环状RNA (circRNA)是一类单链共价闭合的非编码RNA,稳定丰富存在于生物体细胞核、细胞质和体液中,成为近年来卵巢癌调控研究的热点。该文从细胞凋亡、上皮间充质转化、细胞周期、自噬和生物标志物方面系统综述了与卵巢癌调控相关的62个circRNAs,其中包括与卵巢癌顺铂和紫杉烷类化疗耐药显著相关的15个circRNAs;并从竞争性内源RNA、功能蛋白互作、翻译成多肽和蛋白质,以及信号通路方面对circRNA调控卵巢癌及其化疗耐药的分子机制进行了梳理,以期为后续circRNA调控卵巢癌及其化疗耐药的相关研究提供参考。