Novel Biomarker For Early Detection Research Articles

BDNF methylation associated with stress in women: Novel insights in epigenetics and inflammation

The brain-derived neurotrophic factor (BDNF) gene plays an important role in modulating the stress-response axis and inflammation, which can be regulated by epigenetic mechanisms. BNDF methylation has been associated with stress-related psychiatric disorders such as depression, anxiety and post-traumatic stress. Previous studies have reported that stressful events are involved with long-lasting alterations in DNA methylation (DNAm) of the BNDF exon IV promoter, suggesting that glucocorticoids and inflammatory cytokines can regulate this process. We previously found that perceived psychological stress is modulated by inflammatory cytokines, such as interleukin (IL)-6, IL-8 and IL-10, and IL-12p70, suggesting their role in mediating the stress response. However, the epigenetic mechanism mediating this response has yet to be fully understood. In this study, we propose that high perceived stress and high serum levels of inflammatory cytokines may correlate with specific methylation sites within the BNDF exon IV promoter. To address these questions, we conducted a cross-sectional study of 82 adult women teachers working in basic education in Brazil. The perceived stress scale was used to assess stress and blood samples were collected for the measurement of inflammatory markers and BNDF methylation through flow cytometry assay and DNA pyrosequencing, respectively. We detected differentially methylated CpG sites in the BNDF gene, where 5 CpG sites were directly correlated with high stress levels. However, 4 CpG sites showed inverse effects, indicating that changes in methylation levels in those sites could lead to a protective effect on perceived stress. About inflammatory markers, IL-6 and IL-8 were associated with high perceived stress. However, only IL-8 and IL-10 showed simultaneous modulation of perceived stress, while IL-10 and IL12p70 correlated with DNAm. We found that higher levels in IL-10 and IL-12p70 serum decrease methylation in CpG11. A direct relationship was also found to IL-12p70, where higher levels in serum increase methylation in CpG5 and 13, respectively. Taken as a whole, our findings reinforce the hypothesis regarding stress-sensitive regions within the BDNF gene, mainly for CpG5, 11, and 13. In addition to these results, CpG7 and 9 may be regarded as stress-protective regions. Our data suggest that BDNF DNAm in the blood may represent a novel biomarker for early detection of adverse effects of chronic exposure to stress in healthy individuals.

Atypical cells in urine sediment: a novel biomarker for early detection of bladder cancer

Atypical cells in urine sediment: a novel biomarker for early detection of bladder cancer

Retina as a potential biomarker for the early stage of Alzheimer's disease spectrum.

To characterize the retinal microvasculature and structure in subjective cognitive decline (SCD) and identify the potential biomarker for the early stage of the Alzheimer's disease (AD) spectrum. In this study, 35 patients with SCD, 36 with cognitive impairment, and 29 with normal cognition (NC) were enrolled. Optical coherence tomography angiography was employed to assess retinal vascular density, fovea avascular zone area, and retinal thickness. The parameters reflecting retinal perfusion and structure were compared among the three groups. In addition, the association between retinal parameters, cerebral blood flow (CBF), and peripheral blood biomarkers in the SCD stage was analyzed. The superficial vascular complex (SVC) vascular density in the macula and retinal nerve fiber layer thickness in the peripapillary were significantly reduced in individuals with SCD compared to NC. Furthermore, there was a positive correlation between macular ganglion cell complex thickness and CBF in SCD. The retinal microvasculature and structure exhibit alterations in individuals with SCD. Macular ganglion cell complex thickness demonstrates correlations with cerebral perfusion. The retina holds potential as a novel biomarker for early detection of AD.

Proenkephalin A 119-159 as a Novel Biomarker for Early Detection of Delayed Graft Function After Kidney Transplantation

Proenkephalin A 119-159 as a Novel Biomarker for Early Detection of Delayed Graft Function After Kidney Transplantation

Novel conditionally replicating adenovirus-mediated efficient detection of circulating tumor cells in lung cancer patients.

Circulating tumor cells (CTCs) are present in the blood of cancer patients from the early stage of cancer development, and their presence has been correlated with patient prognosis and treatment responses. Accordingly, CTCs have been attracting attention as a novel biomarker for early detection of cancer and monitoring of treatment responses. However, since patients typically have only a few CTCs per milliliter of blood, development of an accurate and highly sensitive CTC detection method is crucial. We previously developed a CTC detection method using a novel conditionally replicating adenovirus (Ad) that expresses green fluorescence protein (GFP) in a tumor cell-specific manner by expressing the E1 gene using a tumor-specific human telomerase reverse transcriptase (hTERT) promoter (rAdF35-142T-GFP). CTCs were efficiently detected using rAdF35-142T-GFP, but GFP expression levels in the CTCs and production efficiencies of rAdF35-142T-GFP were relatively low. In this study, in order to overcome these problems, we developed four types of novel GFP-expressing conditionally replicating Ads and examined their ability to visualize CTCs in the blood samples of lung cancer patients. Among the four types of novel recombinant Ads, the novel conditionally replicating Ad containing the 2A peptide and the GFP gene downstream of the E1A gene and the adenovirus death protein (ADP) gene in the E3 region (rAdF35-E1-2A-GFP-ADP) mediated the highest number of GFP-positive cells in the human cultured tumor cell lines. Titers of rAdF35-E1-2A-GFP-ADP were significantly higher (about 4-fold) than those of rAdF35-142T-GFP. rAdF35-E1-2A-GFP-ADP and rAdF35-142T-GFP efficiently detected CTCs in the blood of lung cancer patients at similar levels. GFP+/CD45- cells (CTCs) were found in 10 of 17 patients (58.8%) for both types of recombinant Ads.

Plasma exosomal hsa_circ_0079439 as a novel biomarker for early detection of gastric cancer.

Due to the poor prognosis of gastric cancer (GC), early detection methods are urgently needed. Plasma exosomal circular RNAs (circRNAs) have been suggested as novel biomarkers for GC. To identify a novel biomarker for early detection of GC. Healthy donors (HDs) and GC patients diagnosed by pathology were recruited. Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing. The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction. The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency. There were 303 participants, including 240 GC patients and 63 HDs, involved in the study. The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs (P < 0.0001). However, the levels of standard serum biomarkers were similar between the two groups. The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers, including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, CA72-4, alpha-fetoprotein, and CA125 (0.8595 vs 0.5862, 0.5660, 0.5360, 0.5082, and 0.5018, respectively). The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment (P < 0.05). Moreover, the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC (EGC) patients than in HDs (P < 0.0001). Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients. Moreover, the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs. Therefore, plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.

169P Urine tumor DNA fragmentation profiles provided a novel biomarker for early detection of prostate cancer

Prostate Cancer is the second most common malignancy worldwide in male. Serum total PSA (tPSA) testing has led to the identification of patients with indolent prostate cancer, and inevitably over-treatment has become a concern. Urine tumor (utDNA) provides new approach for non-invasive early detection of prostate cancer.

VISFATIN AS A BIOMARKER FOR EARLY DETECTION OF GESTATIONAL DIABETESE MELLITUS

Background: The increased levels of visfatin in response to slowly developing resistance to insulin and impairment of glucose metabolism in human body is a well-documented process, beginning early in with uncontrolled diabetes and obesity The objective of present study was to determine the difference between levels of visfatin in the gestational diabetes mellitus cases and pregnancies with normal OGTT. Methods: It was a case control study conducted in Ayub Teaching Hospital Abbottabad. Twenty-eight (n=28) diagnosed cases of gestational diabetes mellitus at various gestational ages (ranging from 11 weeks to 33weeks of pregnancy) were included in the Group I and their levels were compared with non-diabetic normal antenatal cases, Group II (n=32). Blood samples were collected for blood glucose and visfatin levels. Visfatin levels were measured by enzyme-linked immunosorbent assay (ELIZA). Statistical analysis was performed on SPSS-20, and p&lt;0.05 was taken as significant. Results: Pregnant women (n=60) of different gestational age ranging from 4–36 weeks of pregnancy when subdivided into three categories (4–12 weeks, 13–24 weeks, 24–36 weeks respectively), showed statistically significant (p=0.003) differences of serum visfatin levels (10.11±2.982, 1.01±2.634, 1.17±3.102 ng/ml respectively). There were no significant differences in mean value of serum visfatin (p=0.763) according to parity of the patients (0.16±2.892, 0.19±2.883, 1.01±2.736 respectively) in the three trimesters of pregnancy. Conclusion: Visfatin levels were significantly raised in gestational diabetes mellitus as early as first trimester of pregnancy. Increased levels of visfatin can be used as a novel biomarker for early detection of gestational diabetes mellitus. Pak J Physiol 2021;17(4):11?4

MACE-Seq-based coding RNA and TrueQuant-based small RNA profile in breast cancer: tumor-suppressive miRNA-1275 identified as a novel marker

IntroductionDisruption of cellular processes in the breast by abnormally expressed miRNA is characterized to develop cancer. We aimed to identify the differential expression of small RNAs (sRNAs) and mRNAs in formalin-fixed paraffin-embedded (FFPE) tissue of the breast cancer (BC) and normal adjacent tissue (NAT). Another aim is to determine the differential expression of miR-1275 as a novel biomarker for BC and also identify its target genes.MethodsTrueQuant method for analysis of sRNA expression and MACE-sequencing method for analysis of gene expression were used analyzing. The RT-qPCR technique was used to confirm miR-1275 down expression. Target genes of miR-1275 were computationally identified using target prediction sites and also the expression level of them was experimentally determined among the expressed genes.ResultsTrueQuant findings showed that 1400 sRNAs were differentially expressed in the FFPE tissue of two Kurdish cases with BC, as compared to NAT. Among the sRNAs, 29 small RNAs were shown to be significantly downregulated in BC cells. The RT-qPCR results confirmed that miR-1275 was significantly down-expressed in 20 Kurdish cases with BC compared to NAT. However, Overall survival (OS) analysis revealed that the correlation between the expression level of miR-1275 and clinical significance was highly corrected in cases with BC (OS rate: P = 0.0401). The MACE-seq results revealed that 26,843 genes were differentially expressed in the BC tissue compared to NAT, but 7041 genes were displayed in a scatter plot. Furthermore, putative target genes (DVL3, PPP2R2D, THSD4, CREB1, SYT7, and PRKACA) were computationally identified as direct targets of miR-1275 in several target predicted sites. The MACE-seq results revealed that the expression level of these targets was increased in BC tissue compared to NAT. The level of these targets was negatively associated with miR-1275 expression. Finally, the role of down-regulated miR-1275 on its targets in biological mechanisms of BC cells was identified; including cell growth, proliferation, movement, invasion, metastasis, and apoptosis.ConclusionDown-expressed miR-1275, a tumor suppressor, is a novel biomarker for early detection of BC. DVL3, PPP2R2D, THSD4, CREB1, SYT7, and PRKACA are newly identified to be targeted by miR-1275.

Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy.

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

Cyclophilin A (CyPA) as a Novel Biomarker for Early Detection of Diabetic Nephropathy in an Animal Model.

Background and AimType 2 diabetes mellitus (DM) is the most common single cause of the end-stage renal disease (ESRD). Cyclophilin A (CyPA) is an 18-kD protein. The connection between diabetic nephropathy (DN) and the secreted form of CyPA (sCyPA) has been elucidated in this study that aims to investigate sCyPA correlation with renal dysfunction.Materials and MethodsThirty-four male adult Wistar rats weighing 180–220 g were used. Animals were divided into a study group and a control group, 17 rats in each. Streptozotocin (STZ) and nicotine amide were used to damage some pancreatic cells for induction of type 2 DM. Comparison was made between the study and the control groups. Moreover, a comparison was made between the members of the study group before and after induction of DN.ResultsThe rat model that exhibited a higher concentration of urinary sCyPA was detected early in the eighth week. There was a significantly higher level of 24-h urinary CyPA in the study group compared to the control group (p-value=0.004) and there was a significant elevation in the 24-h urinary Cyp-A in the study group after injection of STZ compared to the values before injection (p-value <0.001). Immunohistochemical analysis of renal tissue revealed that the mean expression of CyPA was higher in the study group than in the control group. For the urinary 24-h CYP-A, using a cutoff of 1.15 ng/mL, the accuracy was 72.4%, sensitivity was (77.8%) and specificity was (67%).ConclusionAccording to this animal study, we proved that CyPA is a valuable marker for DN. It is a more sensitive, noninvasive and rapid biomarker for early detection of any renal affection in human diabetic patients.

Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3

BackgroundProstate cancer is one of the leading causes of cancer death in males. Recent studies have reported aberrant expression of lncRNAs in prostate cancer. This study explores the role of LINC00261 in prostate cancer progression.MethodsThe differentially expressed genes, transcription factors, and lncRNAs related to prostate cancer were predicted by bioinformatics analysis. Prostate cancer tissue samples and cell lines were collected for the determination of the expression of LINC00261 by reverse transcription quantitative polymerase chain reaction. The binding capacity of LINC00261 to the transcription factor GATA6 was detected by RIP, and GATA6 binding to the DKK3 promoter region was assessed by ChIP. In addition, luciferase reporter system was used to verify whether LINC00261 was present at the DKK3 promoter. After gain- and loss-of function approaches, the effect of LINC00261 on prostate cancer in vitro and in vivo was assessed by the determination of cell proliferation, invasion and migration as well as angiogenesis.ResultsLINC00261, GATA6, and DKK3 were poorly expressed in prostate cancer. LINC00261 could inhibit transcriptional expression of DKK3 by recruiting GATA6. Overexpression of LINC00261 inhibited prostate cancer cells proliferation, migration, and invasion as well as angiogenesis, which could be reversed by silencing DKK3. Furthermore, LINC00261 could also suppress the tumorigenicity of cancer cells in vivo.ConclusionsOur study demonstrates the inhibitory role of LINC00261 in prostate cancer progression, providing a novel biomarker for early detection of prostate cancer.

Heparanase in myeloma related renal dysfunction: Role in promoting nephrotoxicity and potential as a novel biomarker for early detection.

e20554 Background: Our laboratory previously demonstrated that heparanase (HPSE), an enzyme that cleaves heparan sulfate, upregulates growth factors and their receptors, resulting in enhanced multiple myeloma (MM) growth, chemoresistance, and metastasis. Targeting HPSE therapeutically decreases chemoresistance and relapse. Renal dysfunction is a major problem in MM patients with nearly 50% having renal dysfunction at diagnosis of which 19% are advanced, and 8% require dialysis. There is no specific therapy for myeloma associated renal dysfunction highlighting the need to identify novel mechanisms that lead to the development of targeted therapies. This is the first study to investigate the association between HPSE activity and renal dysfunction in MM patients by utilizing high-sensitivity biomarkers. Methods: Human Kidney 2 (HK-2) cells were treated with HPSE. Necrosis and apoptosis were assessed by flow cytometry. Cell lysates were examined for expression of kidney injury biomarkers by western blotting. HK-2 clusters were co-cultured with MM-spheroids with low or high HPSE. SCID mice were injected with 3 million luciferase-positive myeloma cells with low or high level of HPSE. Kidneys were harvested after 3 weeks and processed for studies. HPSE activity and biomarkers using multiplex magnetic bead ELISA were assessed in peripheral blood from a MM patient with serum creatinine 1.2 mg/dL and a healthy control donor. Results: HPSE induced HK-2 cell necrosis and apoptosis. HPSE induced significant expression by HK-2 cells of KIM-1, NGAL and IGFBP-7. Co-culturing HK-2 organoids with MM-spheroids expressing high HPSE compromised HK-2 organoids survival over 7 days. Damage to HK-2 cells was prevented by HPSE inhibitors Roneparstat or OGT-2115. Kidney tissues from mice harboring HPSE-high myeloma tumors expressed more KIM-1 and NGAL than those harboring HPSE-low myeloma tumors. HPSE activity was 6-fold higher and kidney injury biomarkers were many fold (range 2 – 84) higher in the plasma of a MM patient than in plasma from healthy control. Conclusions: HPSE causes kidney cellular injury which can be detected early by the measurement of high sensitivity biomarkers and can be prevented by treatment with HPSE inhibitors, Roneparstat and OGT-2115. Further studies are ongoing to investigate the association between HPSE activity and renal dysfunction in a larger cohort of MM patients which have been accrued as a part of the UAB-Integrative Molecular And Genetic Epidemiology (IMAGE) Study of Myeloma.

Prefrontal functional connectivity analysis of cognitive decline for early diagnosis of mild cognitive impairment: a functional near-infrared spectroscopy study.

Cognitive decline (CD) is a major symptom of mild cognitive impairment (MCI). Patients with MCI have an increased likelihood of developing Alzheimer's disease (AD). Although a cure for AD is currently lacking, medication therapies and/or daily training in the early stage can alleviate disease progression and improve patients' quality of life. Accordingly, investigating CD-related biomarkers via brain imaging devices is crucial for early diagnosis. In particular, "portable" brain imaging devices enable frequent diagnostic checks as a routine clinical tool, and therefore increase the possibility of early AD diagnosis. This study aimed to comprehensively investigate functional connectivity (FC) in the prefrontal cortex measured by a portable functional near-infrared spectroscopy (fNIRS) device during a working memory (WM) task known as the delayed matching to sample (DMTS) task. Differences in prefrontal FC between healthy control (HC) (n = 23) and CD groups (n = 23) were examined. Intra-group analysis (one-sample t-test) revealed significantly greater prefrontal FC, especially left- and inter-hemispheric FC, in the CD group than in the HC. These observations could be due to a compensatory mechanism of the prefrontal cortex caused by hippocampal degeneration. Inter-group analysis (unpaired two-sample t-test) revealed significant intergroup differences in left- and inter-hemispheric FC. These attributes may serve as a novel biomarker for early detection of MCI. In addition, our findings imply that portable fNIRS devices covering the prefrontal cortex may be useful for early diagnosis of MCI.

Clinical significance of circulating omentin levels in various malignant tumors: Evidence from a systematic review and meta-analysis

Aberrant circulating level of omentin has been reported in various solid tumors. However, whether decreased or increased levels of omentin contribute in cancer risk is remained controversial in different epidemiological studies. This comprehensive meta-analysis of observational studies was conducted to investigate the association between circulating omentin level and human cancer risk. An electronic search of health-related databases, was performed to identify all eligible studies in English, up to July 2019. Combined standard mean difference (SMD) with 95%CI was computed to assess the correlation of omentin levels with human cancer risk in a random effect model. The risk of publication bias was also evaluated using Funnel plot and Egger regression tests. A total of 16 studies with 1106 cases and 3078 healthy controls were included. Pooled SMD analysis based on the cancer type, revealed a strong correlation of omentin level and cancer risk in patients with colorectal (SMD = 2.08, 95%CI: 1.67–2.50, P < 0.001), prostate (SMD = 1.38, 95%CI: 1.15–1.62, P < 0.001), and breast (SMD = −0.78, 95%CI: −1.1, −0.45, P < 0.001) cancers. Elevated circulating omentin levels was also found in cancer patients with BMI ≥ 25 (SMD = 1.33, 95%CI: 0.52–2.15, P = 0.001) indicating a potential role for omentin in development of some obesity-linked cancers. The findings of this meta-analysis indicated a significant association of omentin level with greater risk of colorectal, pancreas, and breast tumors. Circulating omentin level may represent a potential novel biomarker for early detection of colorectal, prostate, and breast cancers especially in overweight/obese subjects. Further prospective well-designed studies are warranted to confirm our findings.

Exploratory Analysis of Plasma Neurotensin as a Novel Biomarker for Early Detection of Colorectal Polyp and Cancer

Earlier detection of colorectal cancer (CRC) results in improved survival. Existing non-invasive biomarkers have suboptimal accuracy. Neurotensin (NTS) is involved in CRC carcinogenesis. This study evaluated the diagnostic potential of plasma NTS for colorectal polyps and cancers. Participants were selected based on national CRC referral guidelines. All subjects underwent colonoscopy. Average plasma concentrations were compared across different diagnostic groups. Predictors for detecting colorectal neoplasia were identified. Receiver operator characteristic (ROC) curve analysis assessed the diagnostic accuracy of NTS. An independent biobank was used as validation group. Of 165 participants, 46 had polyps or CRC. Significantly higher plasma NTS was found in the colonic neoplasia group (603.6 pg/ml vs. 407.2 pg/ml, p < 0.01). Risk factors for colonic polyps or cancers included Loge (plasma NTS concentration) (OR, 2.73; 95% CI, 1.33–5.59, p < 0.01), loge (Age) (OR, 15.49; 95% CI, 2.67–89.66, p < 0.01) and cigarette smoking (OR, 3.49; 95% CI, 1.31–9.26, p = 0.01). Plasma NTS had an optimal sensitivity of 60.4% and specificity of 71.6% for the diagnosis of colorectal polyps and cancers. Similar diagnostic accuracy was obtained in the validation group. Plasma NTS has the potential to be a non-invasive biomarker for colorectal neoplasia. It appears to be more accurate than existing blood markers and is unique in being able to detect precancerous polyps.

The phosphoinositide hydrolase phospholipase C delta1 inhibits epithelial-mesenchymal transition and is silenced in colorectal cancer.

In this study, we found that the phospholipase C delta1 (PLCD1) protein expression is reduced in colorectal tumor tissues compared with paired surgical margin tissues. PLCD1-promoted CpG methylation was detected in 29/64 (45%) primary colorectal tumors, but not in nontumor tissues. The PLCD1 RNA expression was also reduced in three out of six cell lines, due to PLCD1 methylation. The ectopic expression of PLCD1 resulted in inhibited proliferation and attenuated migration of colorectal tumor cells, yet promoted colorectal tumor cell apoptosis in vitro. We also observed that PLCD1 suppressed proliferation and promoted apoptosis in vivo. In addition, PLCD1 induced G1/S phase cell cycle arrest. Furthermore, we found that PLCD1 led to the downregulation of several factors downstream of β-catenin, including c-Myc and cyclin D1, which are generally known to be promoters of tumorigenesis. This downregulation was caused by an upregulation of E-cadherin in colorectal tumor cells. Our findings provide insights into the role of PLCD1 as a tumor suppressor gene in colorectal cancer (CRC), and demonstrate that it plays significant roles in proliferation, migration, invasion, cell cycle progression, and epithelial-mesenchymal transition. On the basis of these results, tumor-specific methylation of PLCD1 could be used as a novel biomarker for early detection and prognostic prediction in CRC.

Salivary Human Chorionic Gonadotropin as a Novel Biomarker for Early Detection of Pregnancy: A Pilot Study.

Context:The role of saliva in detection of pregnancy has not received the due importance it deserves.Aims:The present paper aims at determining the role of saliva in detection of pregnancy using home-based pregnancy detection kits to provide an alternative biofluid that is more user friendly, acceptable, noninvasive, rapid, and easy for home use.Settings and Design:The study was conducted among 35 women visiting a gynecology clinic for confirmation of pregnancy, who gave a history of a missed menstrual cycle not more than 4 weeks.Subjects and Methods:A home-based pregnancy detection kit meant for urinary human chorionic gonadotropin (hCG) detection with 20 mIU specification was used in the study for estimation of salivary hCG. Routine test that was prescribed to the patient such as laboratory-based urine hCG and/or ultrasound examination was used for confirmation of pregnancy status and correlation with the saliva-based result.Results:A positive test was obtained in 74% participants, with a dark band in 43% participants and a light band in 31% participants. A negative result was noted in 26% participants. We observed that salivary hCG estimation showed a 77% accuracy and 23% false-negative results.Conclusions:An astounding 74% of participants showed a positive result with an existing pregnancy kit which indicates a strong plausibility of using salivary hCG as a biomarker for detection of pregnancy. With the findings obtained from our study, we could positively affirm that salivary hCG can be used as a potential, user friendly, and more acceptable biomarker for early detection of pregnancy.

Serum CNPY2 Isoform 2 Represents a Novel Biomarker for Early Detection of Colorectal Cancer

Since early diagnosis is very important for treating CRC, we decided to detect peripheral serum canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform 2 to verify its diagnostic value for CRC patients. Serum samples were collected from 430 CRC patients and 201 healthy controls. Enzyme-linked immunosorbent assay (ELISA) detection kits for CNPY2 isoform 2 were generated and then applied to measure serum CNPY2 isoform 2 concentrations. Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were also measured. The median serum CNPY2 isoform 2 concentrations in all CRC patients were significantly higher than those in the healthy control group (all P<0.001). Those with stage I CRC presented the highest area under the receiver operating characteristic curve (AUC) for CNPY2 isoform 2 [0.707, 95% confidence interval (CI): 0.649-0.765, P<0.001]. The diagnostic efficiency of the combination of CNPY2 isoform 2, CEA and CA19-9 was significantly higher than that of each biomarker detected separately (all P<0.0167).Serum CNPY2 isoform 2 may be a valuable biomarker for the early detection of CRC and presents an improvement in the diagnostic efficiency by combination of CEA and CA19-9. Funding Statement: This study was funded by a grant from the Guangzhou Science and Technology Plan Projects (Health Medical Collaborative Innovation Program of Guangzhou) (grant No. 201400000001-4), the National Natural Science Foundation of China (NO. 81772595), Sun Yat-sen University ClinicalResearch 5010 Program (NO.2015024 and NO. 2013013). Declaration of Interests: The authors declare none. Ethics Approval Statement: This study was performed in accordance with the ethical standards of the World Medical Association Declaration of Helsinki. Study was approved by the Institutional Research Ethics Committee of Sun Yat-sen University Cancer Center (Approval number: B2017-042-01). The informed consents for using tissue samples, before the initial treatment, were obtained from the patients.

Serum CNPY2 isoform 2 represents a novel biomarker for early detection of colorectal cancer.

Since early diagnosis is very important for treating CRC, we decided to detect peripheral serum canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform 2 to verify its diagnostic value for CRC patients. Serum samples were collected from 430 CRC patients and 201 healthy controls. Enzyme-linked immunosorbent assay (ELISA) detection kits for CNPY2 isoform 2 were generated and then applied to measure serum CNPY2 isoform 2 concentrations. Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were also measured. The median serum CNPY2 isoform 2 concentrations in all CRC patients were significantly higher than those in the healthy control group (all P<0.001). Those with stage I CRC presented the highest area under the receiver operating characteristic curve (AUC) for CNPY2 isoform 2 [0.707, 95% confidence interval (CI): 0.649–0.765, P<0.001]. The diagnostic efficiency of the combination of CNPY2 isoform 2, CEA and CA19-9 was significantly higher than that of each biomarker detected separately (all P<0.0167). Serum CNPY2 isoform 2 may be a valuable biomarker for the early detection of CRC and presents an improvement in the diagnostic efficiency by combination of CEA and CA19-9.