Project description:Purpose: Oncologists for pancreatobiliary cancer (PBca) demand a new circulating biomarker superior to carbohydrate antigen 19-9 (CA19-9). This study aimed to identify the serum microRNA signature composed of reproducible and disease-related microRNAs with clinical bioinformatics. Methods: This multicenter study enrolled patients with treatment-naïve PBca and healthy participants. Optimized serum processing condition was evaluated with t-distributed stochastic neighbor embedding (t-SNE) visualization. The serum microRNA candidates were selected in disease association with Weighted Gene Coexpression Network Analysis (WGCNA). A microRNA signature, combination of multiple serum microRNAs, was examined in exploratory, validation and independent validation set. Biology of the diagnostic miRNAs was evaluated using human pancreatic cancer cells. Results: The 284 (healthy 150, PBca 134) of 827 serum samples were processed within 2hr of time-to serum collection, distributed at the same area of t-SNE map, assigned to exploratory set. The 193 optimized samples were assigned to validation (healthy 50, PBca 47) or independent validation set (healthy 50, PBca 46). Index-1 was a combination of the 5 serum microRNAs having disease-association on WGCNA, showed a sensitivity/specificity >80% and an AUC outperforming CA19-9 in exploratory, validation and independent validation set. The AUC of Index-1 for detecting T1 tumor was superior to CA19-9 (0.856 vs. 0.649, p = 0.038). Human pancreatic cancer cells had intra- and extracellular expression of miR-665, a component of Index-1. Transfection of miR-665 to a human pancreatic cancer cell inhibited cell growth. Conclusions: A serum microRNA signature, Index-1, was useful for detecting PBca, which would improve the early diagnosis of PBca.
Project description:BackgroundGastric cancer is a frequent malignant tumor worldwide and its early detection is crucial for curing the disease and enhancing patients' survival rate. This study aimed to assess whether the multi-disciplinary team (MDT) can improve the detection rate of early gastric cancer (EGC).MethodsThe detection rate of EGC at the Digestive Endoscopy Center, Affiliated Hospital, Zunyi Medical College, China between September 2013 and September 2015 was analyzed. MDT for the diagnosis of EGC in the hospital was established in September 2014. The study was divided into 2 time periods: September 1, 2013 to August 31, 2014 (period 1) and September 1, 2014 to September 1, 2015 (period 2).ResultsA total of 60,800 patients' gastroscopies were performed during the two years. 61 of these patients (0.1%) were diagnosed as EGC, accounting for 16.44% (61/371) of total patients with gastric cancer. The EGC detection rate before MDT (period 1) was 0.05% (16/29403), accounting for 9.09% (16/176) of total patients with gastric cancer during this period. In comparison, the EGC detection rate during MDT (period 2) was 0.15% (45/31397), accounting for 23% (45/195) of total patients with gastric cancer during this period (P < 0.05). Univariate and multivariate logistic analyses showed that intensive gastroscopy for high risk patients of gastric cancer enhanced the detection rate of EGC in cooperation with Department of Pathology (OR = 10.1, 95% CI 2.39-43.3, P < 0.05).ConclusionMDT could improve the endoscopic detection rate of EGC.
Project description:Background: Surface-enhanced Raman spectroscopy (SERS) analysis of urine is a promising liquid biopsy technique for cancer detection. However, its clinical translation is hindered by two major challenges that impact classification efficacy. First, the SERS signal of urine is confounded by fluctuations induced by physiological differences in urine composition such as pH and dilution. Second, the molecular origin of the SERS signal of urine is incompletely understood, limiting the interpretability of machine learning classifiers in terms of specific biochemical markers. Methods: In this pilot study, we analyzed urine samples from breast cancer patients (n = 18) and control subjects (n = 10) at three pH levels (5, 7, and 9). Additionally, we analyzed simulated urine mixtures consisting of uric acid, hypoxanthine, xanthine, and creatinine in physiological concentrations to explain the variation in the SERS spectra at different pH values. Results: Urine at pH 9 yielded the most detailed spectral features. The SERS spectral pattern under alkaline pH reflected greater contributions from hypoxanthine, uric acid, and creatinine, while xanthine contributions diminished due to competitive interactions at the SERS substrate surface. Normalizing SERS signals to the creatinine band at 1420 cm-1 effectively mitigated the confounding effects of urine dilution. Conclusions: Optimizing the pH to 9 and normalizing to creatinine significantly enhances the interpretability and accuracy of SERS-based urine analysis for cancer detection. These findings offer important theoretical and practical advancements for the development of SERS-based liquid biopsy tools for cancer detection.
Project description:BackgroundA new circulating biomarker superior to carbohydrate antigen 19-9 (CA19-9) is needed for diagnosing pancreatobiliary cancer (PBca). The aim of this study was to identify serum microRNA (miRNA) signatures comprising reproducible and disease-related miRNAs.MethodsThis multicenter study involved patients with treatment-naïve PBca and healthy participants. The optimized serum processing conditions were evaluated using t-distributed stochastic neighbor embedding (t-SNE) visualization. Serum miRNA candidates for disease association were selected using weighted gene coexpression network analysis (WGCNA). A miRNA signature combining multiple serum miRNAs was tested in exploratory, validation, and independent validation sets. The synthesis and secretion of diagnostic miRNAs were evaluated using human pancreatic cancer cells.ResultsIn total, 284 (150 healthy and 134 PBca) of 827 serum samples were processed within 2 h of blood collection before freezing, distributed in the same area as that in the t-SNE map, and assigned to an exploratory set. The 193 optimized samples were assigned to either the validation (50 healthy, 47 PBca) or independent validation (50 healthy, 46 PBca) set. Index-1, a combination of five serum miRNAs (hsa-miR-1343-5p, hsa-miR-4632-5p, hsa-miR-4665-5p, hsa-miR-665, and hsa-miR-6803-5p) with disease association in WGCNA, showed a sensitivity and specificity of > 80% and an AUC outperforming that of CA19-9 in the exploratory, validation, and independent validation sets. The AUC of Index-1 was superior to that of CA19-9 (0.856 vs. 0.649, p = 0.038) for detecting T1 tumors. miR-665, a component of Index-1, was expressed in human pancreatic cancer cells, and its transfection inhibited cell growth.ConclusionsThe serum miRNA signature Index-1 is useful for detecting PBca and could facilitate the early diagnosis of PBca. These findings can help improve clinical PBca detection by providing an optimized biomarker that overcomes the limitations of the current standard.
Project description:BackgroundA noninvasive, highly sensitive and specific urine test is needed for bladder cancer (BC) diagnosis and surveillance in addition to the invasive cystoscopy. We previously described the diagnostic effectiveness of urinary tyrosine-phosphorylated proteins (UPY) and a new assay (UPY-A) for their measurement in a pilot study. The aim of this work was to evaluate the performances of the UPY-A using an independent cohort of 262 subjects.MethodsUrinary tyrosine-phosphorylated proteins were measured by UPY-A test. The area under ROC curve, cutoff, sensitivity, specificity and predictive values of UPY-A were determined. The association of UPY levels with tumour staging, grading, recurrence and progression risk was analysed by Kruskal-Wallis and Wilcoxon's test. To test the probability to be a case if positive at the UPY-A, a logistic test adjusted for possible confounding factor was used.ResultsResults showed a significant difference of UPY levels between patients with BC vs healthy controls. For the best cutoff value, 261.26 Standard Units (SU), the sensitivity of the assay was 80.43% and the specificity was 78.82%. A statistically significant difference was found in the levels of UPY at different BC stages and grades between Ta and T1 and with different risk of recurrence and progression. A statistically significant increased risk for BC at UPY-A ⩾261.26 SU was observed.ConclusionsThe present study supplies important information on the diagnostic characteristics of UPY-A revealing remarkable performances for early stages and allowing its potential use for different applications encompassing the screening of high-risk subjects, primary diagnosis and posttreatment surveillance.
Project description:Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.
Project description:BackgroundA gastric cancer (GC) diagnosis relies on histopathology. Endoscopy rates are increasing. Helicobacter pylori infection is a major GC risk factor. In an effort to elucidate abundant blood biomarkers, and potentially reduce the number of diagnostic surgical interventions, we investigated sera and biopsies from a cohort of 219 H. pylori positive and negative patients diagnosed with GC, gastritis, and ulcers. This allowed the comparative investigation of the different gastroduodenal diseases, and the exclusion of protein changes resulting from bacterial infection or inflammation of the gastric mucosa when searching for GC-dependent proteins.MethodsHigh-definition mass spectrometry-based expression analysis of tryptically digested proteins was performed, followed by multivariate statistical and network analyses for the different disease groups, with respect to H. pylori infection status. Significantly regulated proteins differing more than two-fold between groups were shortlisted, and their role in gastritis and GC discussed.ResultsWe present data of comparative protein analyses of biopsies and sera from patients suffering from mild to advanced gastritis, ulcers, and early to advanced GC, in conjunction with a wealth of metadata, clinical information, histopathological evaluation, and H. pylori infection status. We used samples from pre-malignant stages to extract prospective serum markers for early-stage GC, and present a 29-protein marker panel containing, amongst others, integrin β-6 and glutathione peroxidase. Furthermore, ten serum markers specific for advanced GC, independent of H. pylori infection, are provided. They include CRP, protein S100A9, and kallistatin. The majority of these proteins were previously discussed in the context of cancer or GC. In addition, we detected hypoalbuminemia and increased fibrinogen serum levels in gastritis.ConclusionTwo protein panels were suggested for the development of multiplex tests for GC serum diagnostics. For most of the elements contained in these panels, individual commercial tests are available. Thus, we envision the design of multi-protein assays, incorporating several to all of the panel members, in order to gain a level of specificity that cannot be achieved by testing a single protein alone. As their development and validation will take time, gastritis diagnosis based on the fibrinogen to albumin serum ratio may be a quick way forward. Its determination at the primary/secondary care level for early diagnosis could significantly reduce the number of referrals to endoscopy. Preventive measures are in high demand. The protein marker panels presented in this work will contribute to improved GC diagnostics, once they have been transferred from a research result to a practical tool.