Biomarkers For Diagnosis Of Cancer Research Articles

Implications of RNA pseudouridylation for cancer biology and therapeutics: a narrative review.

Pseudouridine (Ψ), a C5-glycoside isomer of uridine, stands as one of the most prevalent RNA modifications in all RNA types. Distinguishing from the C-N bond linking uridine to ribose, the link between Ψ and ribose is a C-C bond, endowing Ψ modified RNA distinct properties and functions in various biological processes. The conversion of uridine to Ψ is governed by pseudouridine synthases (PUSs). RNA pseudouridylation is implicated in cancer biology and therapeutics. In this review, we will summarize the methods for detecting Ψ, the process of Ψ generation, the impact of Ψ modification on RNA metabolism and gene expression, the roles of dysregulated Ψ and pseudouridine synthases in cancers, and the underlying mechanism. We conducted a comprehensive search of PubMed from its inception through February 2024. The search terms included "pseudouridine"; "pseudouridine synthase"; "PUS"; "dyskerin"; "cancer"; "tumor"; "carcinoma"; "malignancy"; "tumorigenesis"; "biomarker"; "prognosis" and "therapy". We included studies published in peer-reviewed journals that focused on Ψ detection, specific mechanisms involving Ψ and PUSs, and prognosis in cancer patients with high Ψ expression. We excluded studies lacking sufficient methodological details or appropriate controls. Ψ has been recognized as a significant biomarker in cancer diagnosis and prognosis. Abnormal Ψ modifications mediated by various PUSs result in dysregulated RNA metabolism and impaired RNA function, promoting the development of various cancers. Overexpression of PUSs is common in cancer cells and predicts poor prognosis. PUSs inhibition arrests cell proliferation and enhances apoptosis in cancer cells, suggesting PUS-targeting cancer therapy may be a potential strategy in cancer treatment. High Ψ levels in serum, urine, and saliva may suggest cancer, but do not specify the type, requiring additional lab markers and imaging for accurate diagnosis. Standardized detection methods are also crucial for reliable results. PUSs are linked to cancer, but more researches are needed to understand their mechanisms in different cancers. Anticancer treatments targeting PUSs are still under developed.

Quantitative detection of circular RNA and microRNA at point-of-care using droplet digital CRISPR/Cas13a platform

Circular RNA (circRNA) and microRNA (miRNA) are both non-coding RNAs (ncRNAs) that serve as biomarkers for cancer diagnosis and prognosis. Quantitative detection of these ncRNAs is of particular importance to elucidate the functional mechanisms and evaluate their potential as biomarkers. However, the inherent structures of circRNA and miRNA are different from the mRNA, conventional qRT-PCR is unsuitable for the detection of these ncRNAs. Here, we propose a sensitive method for quantitative detection of circRNA and miRNA using polydisperse droplet digital CRISPR/Cas13a (PddCas13a). It can achieve limits of detection (LOD) as low as ∼10 aM without polymerase-based amplification. To efficiently detect the circRNA and miRNA in real samples, we use a chemically modified crRNA to enhance the stability of crRNA and improve the performance of Cas13a in complex environments containing contaminants. By integrating an extraction-free procedure with PddCas13a, we experimentally demonstrate the applicability of PddCas13a by testing clinical samples. Furthermore, we develop an automated and portable instrument for PddCas13a and verify its applicability for the detection of circRNA and miRNA from exosomes in point-of-care (POC) setting. This is the first report to detect the circRNA and miRNA simultaneously in POC setting. We envision this platform could promote the research of ncRNAs.

Multifaceted role of microRNA-301a in human cancer: from biomarker potential to therapeutic targeting.

With the growing data on microRNA (miRNA) expression in tissues and circulation, there is increasing evidence for the potential of microRNAs to serve as biomarkers in cancer diagnosis and prognosis, as well as novel therapeutic targets. The expression level of miRNA-301a (miR-301a) is altered in a wide range of human tumor types, and numerous studies have revealed the roles of miR-301a in tumorigenesis and tumor progression. Herein, we comprehensively summarize, compare, and contrast the research advancements on the role of miR-301a in different cancers. Differential expression patterns of miR-301a in tissues and biofluids are implicated in cancer diagnosis, treatment response, and prognosis. MiR-301a modulates the expression of multiple genes, other noncoding RNAs, and signaling cascade via direct or indirect regulation in human cancer proliferation, migration, invasion, angiogenesis, and radio- or chemotherapy resistance. Cancer cell-associated miR-301a affects the tumor microenvironment through the alteration of immune function and cancer metabolism. These findings highlight the functional roles, clinical implications, and therapeutic relevance of miR-301a in various human cancers.

NSUN2-mediated RNA methylation: Molecular mechanisms and clinical relevance in cancer

Cancer remains a leading cause of morbidity and mortality worldwide, necessitating the ongoing investigation of molecular targets for improved diagnosis, prognosis, and therapy. Among these targets, RNA modifications, particularly N5-methylcytosine (m5C) in RNA, have emerged as critical regulators of gene expression and cellular functions. NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is a key enzyme in m5C modification, significantly influencing various biological processes and tumorigenesis. NSUN2 methylates multiple RNA species, including transfer RNAs (tRNAs), messenger RNAs (mRNAs), and non-coding RNAs, impacting RNA stability, translation efficiency, and cellular stress responses. These modifications, in turn, affect cell proliferation, differentiation, and survival. In cancer, NSUN2 is frequently upregulated, associated with aggressive tumor phenotypes, poor prognosis, and therapy resistance. Its role in oncogenic signaling pathways further underscores its importance in cancer biology. This review offers a comprehensive overview of NSUN2's role in cancer, focusing on its involvement in RNA methylation and its implications for tumor initiation and progression. Additionally, we explore the potential of NSUN2 as a biomarker for cancer diagnosis and prognosis, and its promise as a therapeutic target.

Double hook-type aptamer-based colorimetric and electrochemical biosensor enables rapid and robust analysis of EpCAM expression

Epithelial cell adhesion molecule (EpCAM), which is overexpressed in breast cancer cells and participates in cell signaling, migration, proliferation, and differentiation, has been utilized as a biomarker for cancer diagnosis and therapeutic prognosis. Here, a dual-signal readout nonenzymatic aptasensor is fabricated for the evaluation of EpCAM at the level of three breast cancer cell lines. The central principle of this enzyme-free aptasensor is the use of double hook-type aptamers (SYL3C and SJ3C2)-functionalized magnetic iron oxide (Fe3O4) as capture probes and quasi-CoFe prussian blue analogs (QCoFe PBAs) as nonenzymatic signal probes for colorimetric and electrochemical analysis. Following ligand detachment, the CoFe PBA was transformed to QCoFe PBA (calcined at 350 °C for 1 h), with its metal active sites exposed by controllable pyrolysis. We found that the enhanced sensitivity was attributed to the resonance effect of QCoFe PBA with the remarkable enzymatic properties. The dual-signal readout nonenzymatic aptasensor exhibited limits of detection for EpCAM as low as 0.89 pg mL−1 and 0.24 pg mL−1, within a wide linear range from 0.001 to 100 ng mL−1, respectively. We successfully employed this nonenzymatic aptasensor for monitoring EpCAM expression in three breast cancer cell lines, which provides an economical and robust alternative to costly and empirical flow cytometry. The dual-signal readout nonenzymatic aptasensor provides rapid, robust, and promising technological support for the accurate management of tumors.

Soluble CD40 Ligand as a Promising Biomarker in Cancer Diagnosis.

Cancer remains a significant challenge in medicine due to its complexity and heterogeneity. Biomarkers have emerged as vital tools for cancer research and clinical practice, facilitating early detection, prognosis assessment, and treatment monitoring. Among these, CD40 ligand (CD40L) has gained attention for its role in immune response modulation. Soluble CD40 ligand (sCD40L) has shown promise as a potential biomarker in cancer diagnosis and progression, reflecting interactions between immune cells and the tumor microenvironment. This review explores the intricate relationship between sCD40L and cancer, highlighting its diagnostic and prognostic potential. It discusses biomarker discovery, emphasizing the need for reliable markers in oncology, and elucidates the roles of CD40L in inflammatory responses and interactions with tumor cells. Additionally, it examines sCD40L as a biomarker, detailing its significance across various cancer types and clinical applications. Moreover, the review focuses on therapeutic interventions targeting CD40L in malignancies, providing insights into cellular and gene therapy approaches and recombinant protein-based strategies. The clinical effectiveness of CD40L-targeted therapy is evaluated, underscoring the need for further research to unlock the full potential of this signaling pathway in cancer management.

Liquid Biopsies Based on Cell-Free DNA Integrity as a Biomarker for Cancer Diagnosis: A Meta-Analysis.

Liquid biopsies have been identified as a viable source of cancer biomarkers. We aim to evaluate the diagnostic accuracy of cell-free DNA integrity (cfDI) in liquid biopsies for cancer. A comprehensive literature search was conducted through PubMed, Embase, Web of Science, and Cochrane Library up to June 2024. Seventy-two study units from forty-six studies, comprising 4286 cancer patients, were identified and evaluated. The Quality Assessment for Studies of Diagnostic Accuracy-2 (QUADAS-2) was used to assess study quality. Meta-regression analysis was employed to investigate the underlying factors contributing to heterogeneity, alongside an evaluation of publication bias. The bivariate random-effect model was utilized to compute the primary diagnostic outcomes and their corresponding 95% confidence intervals (CIs). The pooled sensitivity, specificity, and positive and negative likelihood ratios of cfDI in cancer diagnosis were 0.70 and 0.77, 3.26 and 0.34, respectively. The overall area under the curve was 0.84, with a diagnostic odds ratio of 10.63. This meta-analysis suggested that the cfDI index has a promising potential as a non-invasive and accurate diagnostic tool for cancer. Study registration: The study was registered at PROSPERO (reference No. CRD42021276290).

The Potential MicroRNA Diagnostic Biomarkers in Oral Squamous Cell Carcinoma of the Tongue.

Oral squamous cell carcinoma (OSCC) of the tongue is a common type of head and neck malignancy with a poor prognosis, underscoring the urgency for early detection. MicroRNAs (miRNAs) have remarkable stability and are easily measurable. Thus, miRNAs may be a promising biomarker candidate among biomarkers in cancer diagnosis. Biomarkers have the potential to facilitate personalized medicine approaches by guiding treatment decisions and optimizing therapy regimens for individual patients. Utilizing data from The Cancer Genome Atlas, we identified 13 differentially expressed upregulated miRNAs in OSCC of the tongue. Differentially expressed miRNAs were analyzed by enrichment analysis to reveal underlying biological processes, pathways, or functions. Furthermore, we identified miRNAs associated with the progression of OSCC of the tongue, utilizing receiver operating characteristic analysis to evaluate their potential as diagnostic biomarkers. A total of 13 upregulated miRNAs were identified as differentially expressed in OSCC of the tongue. Five of these miRNAs had high diagnostic power. In particular, miR-196b has the potential to serve as one of the most effective diagnostic biomarkers. Then, functional enrichment analysis for the target gene of miR-196b was performed, and a protein-protein interaction network was constructed. This study assessed an effective approach for identifying miRNAs as early diagnostic markers for OSCC of the tongue.

Identification of RFC4 as a potential biomarker for pan-cancer involving prognosis, tumour immune microenvironment and drugs.

RFC4 is required for DNA polymerase δ and DNA polymerase ε to initiate DNA template expansion. Downregulated RFC4 inhibits tumour proliferation by causing S-phase arrest and inhibiting mitosis, resulting in the reduction of tumour cells. RFC4 has been implicated that it plays an important role in the initiation and progression of cancers, but a comprehensive analysis of the role of RFC4 in cancer has not been performed. We comprehensively analysed the expression, prognosis, methylation level, splicing level, relationship of RFC4 and immune infiltration, and pan-cancer immunotherapy response used various databases (including TCGA, GTEx, UALCAN, Oncosplicing, TIDE, TISCH, HPA and CAMOIP), and experimented its biological function in HCC. Through pan-cancer analysis, we found that RFC4 is significantly upregulated in most tumours. The tumour patients with high expression of RFC4 have poor prognosis. The methylation level and variable splicing level of RFC4 were abnormal in most tumours compared with the adjacent tissues. Furthermore, RFC4 was closely associated with immune cell infiltration in various cancers. RFC4 was significantly co-expressed with immune checkpoints and other immune-related genes. The expression of RFC4 could indicate the immunotherapy efficacy of some tumours. The RFC4 expression was associated with sensitivity to specific small molecule drugs. Cell experiments have shown that downregulated RFC4 can inhibit cell cycle and tumour cell proliferation. We conducted a systematic pan-cancer analysis of RFC4, and the results showed that RFC4 can serve as a biomarker for cancer diagnosis and prognosis. These findings open new perspectives for precision medicine.

Breast cancer clinical outcomes and tumor immune microenvironment: cross-dialogue of multiple epigenetic modification profiles.

The discovery of RNA methylation alterations associated with cancer holds promise for their utilization as potential biomarkers in cancer diagnosis, prognosis, and prediction. RNA methylation has been found to impact the immunological microenvironment of tumors, but the specific role of methylation-related genes (MRGs), particularly in breast cancer (BC), the most common cancer among women globally, within the tumor microenvironment remains unknown. In this study, we obtained data from TCGA and GEO databases to investigate the expression patterns of MRGs in both genomic and transcriptional domains in BC. By analyzing the data, we identified two distinct genetic groupings that were correlated with clinicopathological characteristics, prognosis, degree of TME cell infiltration, and other abnormalities in MRGs among patients. Subsequently, an MRG model was developed to predict overall survival (OS) and its accuracy was evaluated in BC patients. Additionally, a highly precise nomogram was created to enhance the practical usability of the MRG model. In low-risk groups, we observed lower TBM values and higher TIDE scores. We further explored how MRGs influence a patient's prognosis, clinically significant characteristics, response to therapy, and the TME. These risk signatures have the potential to improve treatment strategies for BC patients and could be applied in future clinical settings. Moreover, they may also be utilized to determine prognosis and biological features in these patients.

Comparison of trace elements in peripheral blood and bone marrow of newly diagnosed multiple myeloma patients.

Trace elements are essential micronutrients for the human body. Their roles are indispensable, as they are involved in a wide range of vital biological processes. In this study, we aimed to evaluate alterations in trace elements in the blood and bone marrow serum of patients with newly diagnosed multiple myeloma (NMM). The levels of zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), arsenic (As), boron (B), nickel (Ni), silicon (Si) and chromium (Cr) were analyzed in the venous blood samples of the patient group comprising 70 patients with NMM (41 males and 29 females) and compared to those in the control group comprising 30 individuals (18 males and 12 females). In addition, trace element levels were analyzed in bone marrow samples from the patient group. Blood and bone marrow serum levels were quantified using inductively coupled plasma optical emission spectrometry. When the blood samples of the patient and control groups were compared: Zn (p = 0.011), Fe (p = 0.008), Mn (p = 0.046), Se (p < 0.001), As (p < 0.001), Ni (p < 0.001) and Cr (p < 0.001) levels were significantly higher in the patient group than in the control group. Higher Zn, Fe, Mn, Se, As, Ni and Cr levels in the NMM patients suggest that alterations of trace elements could be predisposing factor that initiates the malignant process. The relationship between malignancies and trace elements is crucial for the development of adjuvant therapy strategies and preventive medicine and as biomarkers for cancer diagnosis. Therefore, there is a need for studies examining the relationship between hematological malignancies and trace elements.

Smartphone-based device for rapid and single-step detection of piRNA–651 using anti-DNA:RNA hybrid antibody and enzymatic signal amplification

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs/piRs) are a class of small noncoding RNAs that play a crucial role in regulating various biological processes, including carcinogenesis. One specific piRNA, piR–651, has been reported to be overexpressed in both human blood serum and solid cancer tissues, that can be used a viable biomarker in cancer diagnosis. Early diagnosis of cancer can help reduce the burden of the disease and improve survival rates. In the present work, we report for the first time a smartphone-based colorimetric biosensor for highly sensitive and specific detection of piR–651 thanks to an enzymatic signal amplification, which yielded high colorimetric intensities. Indeed, a heteroduplex DNA:RNA was formed in the presence of piR–651 with the capture DNA probe immobilized on the magnetic beads for easy magnetic separation. Then, a HRP tethered to anti-DNA:RNA (S9.6) was used to reveal the DNA-RNA heteroduplex formed by catalyzing the oxidation of TMB substrate into colorimetric TMBox, which absorbs at 630 nm. The absorbance is positively proportional to the piR–651 concentrations. On the other hand, the colorimetric product of the assay can be photographed with a smartphone camera and analyzed using ImageJ software. Using a smartphone and under optimal conditions, the biosensor responded linearly to the logarithm of piRNA–651 from 8 fM to 100 pM with a detection limit of 2.3 fM and discriminates against other piRNAs. It was also successfully applied to the determination of piRNA–651 levels in spiked human serum.

Potential role of lncRNA LOXL1-AS1 in human cancer development: a narrative review.

Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs consisting of more than 200 nucleotides that are widely involved in various physiological and pathobiological processes in the body. LncRNA plays a crucial role in tumorigenesis and development with its unique functions, such as playing a role in a variety of biological processes of malignant tumors as a cancer-promoting factor or a cancer-suppressor factor. Lysyl oxidase-like protein 1-antisense RNA1 (LOXL1-AS1) is a novel functional lncRNA recently reported. This article reviews the current findings on the role of LOXL1-AS1 in cancer, and discusses the potential clinical significance and application prospects, in order to provide a theoretical basis and reference for the clinical diagnosis, treatment and screening of prognostic markers for malignant tumors. The PubMed and Embase databases were searched using the keywords "cancer" or "tumor" or "neoplasm" and "LOXL1-AS1" for publications from 2018 to the present. The English literature was searched, with a focus on relevant articles. These articles validated the role and mechanism of LOXL1-AS1 in different cancers. LOXL1-AS1 is a recently reported novel lncRNA, which is abnormally expressed and upregulated in more than ten cancers, and is positively correlated with adverse clinical features and poor prognosis in cancer patients. LOXL1-AS1 competently binds to a variety of microRNAs to regulate the expression of downstream target genes and regulate related signaling pathways, including proliferation, migration, invasion and inhibition of malignant biological behaviors such as apoptosis. LOXL1-AS1 is expected to become a novel biomarker for cancer diagnosis and treatment, with great potential as an independent prognostic indicator.

Abstract 1564: NEU4-mediated desialylation ignites the oncogenic receptors for the dissemination of ovarian carcinoma

Abstract Background: Glycosylation profoundly influences the interactions between cancer cells and microenvironmental stromal cells during the peritoneal disseminated metastasis of ovarian carcinoma (OC), which is the major cause of cancer-related death. Although the characteristic cancer glycoconjugates are widely used as biomarkers for cancer diagnosis, our knowledge about cancer glycome remains quite fragmented due to the technique limitations in analyzing glycan chains with tremendous structural and functional heterogeneity. Method: Given the dysregulated cancer glycome is defined by the altered glycosylation machinery, here we performed a systematic loss-of-function screen on 498 genes involved in glycosylation for key regulators of OC dissemination. We identified neuraminidase 4 (NEU4), an enzyme capable of hydrolyzing terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. What’s more, we also identified membrane proteins whose sialylation was able to be modified by NEU4 in OC cells by pull down and mass spectrum to investigate the functional significance of NEU4-mediated desialylation. Results: In human patients with high-grade serous OC (HGSOC), increased NEU4 was detected in the disseminated OC cells when compared with that in the primary tumor cells, which significantly correlated with the worse survival. Among three alternative splice-generated isoforms of human NEU4, we revealed that only the plasma membrane-localized NEU4 isoform 2 (NEU4-iso2) and intracellular isoform 3 promoted the peritoneal dissemination of OC by enhancing the cell motility and epithelial-mesenchymal transition. We also identified NEU4-iso2-regulated cell surface glycoproteome and found that NEU4-iso2 desialylated the epithelial growth factor receptor (EGFR), in particular at N196 residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Conclusion: Our results provide new insights into how the OC glycome is dysregulated by NEU4 during OC progression and reveals a functionally important glycosite on EGFR for its abnormal activation in cancer. Citation Format: Jie Shi, Rui Zhou, Shuo Wang, Yuxin Liu, Baorui Tian, Yanhua Liu, YaNan Chen, Taoyu Hu, Yuhao Mu, Shufan Wang, Xintao Shao, Jie Yan, Pengpeng Qu, Wei Ding, Shuang Yang, Yi Shi, Jia Li, Longlong Wang. NEU4-mediated desialylation ignites the oncogenic receptors for the dissemination of ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1564.

Into the era of mycobiome-driven cancer research

The cancer mycobiome has recently become a research hotspot. While the intratumor mycobiota is implicated in cancer initiation and progression, the gut mycobiota functions as biomarkers for cancer diagnosis and treatment. In this forum article we highlight the involvement of the mycobiome in correlation-, causation-, and prediction-oriented cancer research and discuss the potential of this burgeoning field.

Flexible-Arranged Biomimetic Array Integrated with Parallel Entropy-Driven Circuits for Ultrasensitive, Multiple, and Reliable Detection of Cancer-Related MicroRNAs.

With the emergence of microRNA (miRNA) as a promising biomarker in cancer diagnosis, it is significant to develop multiple analyses of miRNAs. However, it still faces difficulties in ensuring the sensitivity and accuracy during multiplex detection owing to the low abundance and experimental deviation of miRNAs. In this work, a flexible-arranged biomimetic array integrated with parallel entropy-driven circuits (EDCs) was developed for ultrasensitive, multiplex, reliable, and high-throughput detection of miRNAs. The biomimetic array was fabricated by arrangement of various photonic crystals (PCs) for adjustable photonic band gaps (PBGs) and specific fluorescence enhancement. Meanwhile, two cancer-related miRNAs and one reference miRNA were introduced as multiple analytes as a proof-of-concept. The parallel EDCs with negligible crosstalk were designed based on the modular property. Because of the one-to-one match between the emitted fluorescence of parallel EDCs and the PBGs of the flexible-arranged biomimetic array, the generated fluorescence signal triggered by target miRNAs can be enhanced on the corresponding domain of the array. Furthermore, the amplified signal of the array was detected with high-throughput scanning, which could reveal specific information on cancer-related miRNAs as well as reference miRNA, enhancing the abundance and reliability of the analysis. The proposed array has the merits of a modular design, flexible deployment, simple operation (nonenzymatic and isothermal), improved accuracy, high sensitivity, and multiplex analysis, showing potential in disease diagnosis.

Metabolomic landscape of overall and common cancers in the UK Biobank: A prospective cohort study.

Information about the NMR metabolomics landscape of overall, and common cancers is still limited. Based on a cohort of 83,290 participants from the UK Biobank, we used multivariate Cox regression to assess the associations between each of the 168 metabolites with the risks of overall cancer and 20 specific types of cancer.Then, we applied LASSO to identify important metabolites for overall cancer risk and obtained their associations using multivariate cox regression. We further conducted mediation analysis to evaluate the mediated role of metabolites in the effects of traditional factors on overall cancer risk. Finally, we included the 13 identified metabolites as predictors in prediction models, and compared the accuracies of our traditional models. We found that there were commonalities among the metabolic profiles of overall and specific types of cancer: the top 20 frequently identified metabolites for 20 specific types of cancer were all associated with overall cancer; most of the specific types of cancer had common identified metabolites. Meanwhile, the associations between the same metabolite with different types of cancer can vary based on the site of origin. We identified 13 metabolic biomarkers associated with overall cancer, and found that they mediated the effects of traditional factors. The accuracies of prediction models improved when we added 13 identified metabolites in models. This study is helpful to understand the metabolic mechanisms of overall and a wide range of cancers, and our results also indicate that NMR metabolites are potential biomarkers in cancer diagnosis and prevention.

Status and trends of RGS16 based on data visualization analysis: A review.

G-protein signaling regulator 16 (RGS16) has been confirmed that RGS16 is associated with cancer, neurodegenerative diseases, and cardiovascular diseases. Moreover, many studies have shown that RGS16 can be used as a biomarker for cancer diagnosis and prognosis. We used CiteSpace and VOS viewer software to perform a bibliometric analysis of 290 publications in the core collection of Web of Science. All the articles come from 399 institutions, including 618 authors, 179 journals, 40 countries, 115 keywords, 1 language, two types of papers, and reviews. The United States has the largest number of publications. The Research Center of Allergy and Infectious Diseases (NIAID) publishes the most papers, Emory University is the most recent of all institutions with the most recent results in the RGS16 study. Cell biology is the most studied discipline, and the most studied topic is migration. Drury published RGS16-related articles with the most citations (n = 15), and Berman published articles with the most citations (n = 106). The biological applications of RGS16 are currently a hot area of RGS16 research, including inflammation, cancer, ulcerative colitis, metabolic acidosis, platelet activation, and thrombosis. The current scientometrics study provides an overview of RGS16 research from 1995 to 2022. This study provides an overview of current and potential future research hotspots in the field of RGS16 and can be used as a resource for interested researchers.

Exosomal long non-coding RNA MALAT1: a candidate of liquid biopsy in monitoring of Wilms' tumor.

Wilms' tumor (WT) is a rare kidney cancer that primarily affects children. Exosomes are extracellular vesicles that cargo nucleic acids, proteins,etc. for cellular communication. Long non-coding RNAs (lncRNAs) have utility as biomarkers for cancer diagnosis, prognosis, and disease monitoring. We hypothesize that expression of lncRNA, metastasis-associated lung adenocarcinoma transcript-1(MALAT1), is dysregulated and possibly trafficked within exosomes to influence the tissue microenvironment for metastasis and recurrence of WT. We investigated the expression of MALAT1 in thirty WT samples by qPCR. Exosomes were isolated using a precipitated and affinity-binding-based kit, and characterized using TEM, NTA, and DLS. Mean number of exosomes was 9.01×108/mL in primary culture, 1.64×108/mL in urine, and 4.65×108/plasma:400µl. Average yield of total RNA was 1.28µg (primary-culture supernatant:1ml), 1.47µg (Urine:1ml), 1.65µg (Plasma:400 µL). We quantified MALAT1 in exosomes derived from these sources in patients of WT. Expression of MALAT1 was significantly downregulated (p=0.008) in WT samples. This is the first study that demonstrated the presence of lncRNA MALAT1 in various invasive and non-invasive samples of patients with WT(primary tissue culture, urine, and plasma samples).

Tissue of origin prediction for cancer of unknown primary using a targeted methylation sequencing panel

RationaleCancer of unknown primary (CUP) is a group of rare malignancies with poor prognosis and unidentifiable tissue-of-origin. Distinct DNA methylation patterns in different tissues and cancer types enable the identification of the tissue of origin in CUP patients, which could help risk assessment and guide site-directed therapy.MethodsUsing genome-wide DNA methylation profile datasets from The Cancer Genome Atlas (TCGA) and machine learning methods, we developed a 200-CpG methylation feature classifier for CUP tissue of origin prediction (MFCUP). MFCUP was further validated with public-available methylation array data of 2977 specimens and targeted methylation sequencing of 78 Formalin‐fixed paraffin‐embedded (FFPE) samples from a single center.ResultsMFCUP achieved an accuracy of 97.2% in a validation cohort (n = 5923) representing 25 cancer types. When applied to an Infinium 450 K array dataset (n = 1052) and an Infinium EPIC (850 K) array dataset (n = 1925), MFCUP achieved an overall accuracy of 93.4% and 84.8%, respectively. Based on MFCUP, we established a targeted bisulfite sequencing panel and validated it with FFPE sections from 78 patients of 20 cancer types. This methylation sequencing panel correctly identified tissue of origin in 88.5% (69/78) of samples. We also found that the methylation levels of specific CpGs can distinguish one cancer type from others, indicating their potential as biomarkers for cancer diagnosis and screening.ConclusionOur methylation-based cancer classifier and targeted methylation sequencing panel can predict tissue of origin in diverse cancer types with high accuracy.