Salivary microRNAs May Be A Valuable Biomarker To Detect Resectable Pancreatic Cancer
ABSTRACT: Early surgery is vital in the treatment of highly fatal pancreatic cancer (PC). But there is no valuable and non-invasive biomarker to screen PC currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary microRNAs (miRNAs) can act as a biomarker to detect resectable PC. By Agilent microarray salivary miRNAs were profiled from saliva samples from 8 patients with resectable PC and 8 healthy controls. Candidate biomarkers discovered from the profile were subjected to validation by qPCR.
Project description:Tissue microRNAs (miRNAs) can detect cancers and predict prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs share similar expression profiles. In this study, we investigated the diagnostic value of salivary miRNAs (including whole saliva and saliva supernatant) for detection of esophageal cancer. By Agilent microarray, six deregulated miRNAs from whole saliva samples from seven patients with esophageal cancer and three healthy controls were selected. The six selected miRNAs were subjected to validation of their expression levels by RT-qPCR using both whole saliva and saliva supernatant samples from an independent set of 39 patients with esophageal cancer and 19 healthy controls.
Project description:Sensitive and non-invasive biomarkers for pancreatic cancer (PC) are lacking. We aimed to identify salivary long non-coding RNAs (lncRNAs) as biomarkers in diagnosis of resectable PC. Five well-documented lncRNAs: H19, HOTAIR, HOTTIP, MALAT1, PVT1, which are most closely associated with pancreatic cancer from previous studies were selected as putative lncRNA biomarkers. Their expression in pancreatic tissues and saliva of cancer patients and healthy controls was measured by quantification polymerase chain reaction (qPCR). Compared with benign pancreatic tumour (BPT) and normal pancreatic tissues (NPT), HOTAIR, HOTTIP and PVT1 were significantly up-regulated in pancreatic cancer tissues (PCT). As compared to BPT or healthy groups, the salivary levels of HOTAIR and PVT1 were significantly higher in PC group. They were significantly reduced after the curative pancreatectomy. Both salivary lncRNAs distinguished PC patients from healthy controls and BPT patients with sensitivities and specificities ranging from 60-97%. The expression of salivary HOTAIR and PVT1 did not differ significantly between healthy controls and any one of eight leading cancers worldwide. Collectively, our findings indicate that salivary HOTAIR and PVT1 show potential as novel non-invasive biomarkers for detecting PC.
Project description:Detection of pancreatic cancer (PC) at a resectable stage is still difficult because of the lack of accurate detection tests. The development of accurate biomarkers in low or non-invasive biofluids is essential to enable frequent tests, which would help increase the opportunity of PC detection in early stages. Polyamines have been reported as possible biomarkers in urine and saliva samples in various cancers. Here, we analyzed salivary metabolites, including polyamines, using capillary electrophoresis-mass spectrometry. Salivary samples were collected from patients with PC (n = 39), those with chronic pancreatitis (CP, n = 14), and controls (C, n = 26). Polyamines, such as spermine, N?-acetylspermidine, and N?-acetylspermine, showed a significant difference between patients with PC and those with C, and the combination of four metabolites including N?-acetylspermidine showed high accuracy in discriminating PC from the other two groups. These data show the potential of saliva as a source for tests screening for PC.
Project description:BACKGROUND:Although genes have been previously detected in pancreatic cancer (PC), aberrant genes that play roles in resectable pancreatic cancer should be further assessed. METHODS:Messenger RNA samples and clinicopathological data corrected with PC were downloaded from The Cancer Genome Atlas (TCGA). Resectable PC patients were randomly divided into a primary set and a validation set. Univariable Cox regression analysis, lasso-penalized Cox regression analysis, and multivariable Cox analysis were implemented to distinguish survival-related genes (SRGs). A risk score based on the SRGs was calculated by univariable Cox regression analysis. A genomic-clinical nomogram was established by integrating the risk score and clinicopathological data to predict overall survival (OS) in resectable PC. RESULTS:Five survival-related genes (AADAC, DEF8, HIST1H1C, MET, and CHFR) were significantly correlated with OS in resectable PC. The resectable PC patients, based on risk score, were sorted into a high-risk group that showed considerably unfavorable OS (p <?0.001) than the low-risk group, in both the primary set and the validation set. The concordance index (C-index) was calculated to evaluate the predictive performance of the nomogram were respectively in the primary set [0.696 (0.608-0.784)] and the validation set [0.682 (0.606-0.758)]. Additionally, gene set enrichment Analysis discovered several meaningful enriched pathways. CONCLUSION:Our study identified five prognostic gene biomarkers for OS prediction and which facilitate postoperative molecular target therapy for the resectable PC, especially the nomic-clinical nomogram which may be used as an effective model for the postoperative OS evaluation and also an optimal therapeutic tool for the resectable PC.
Project description:Pancreatic cancer (PC) has a poor prognosis owing to difficulties in the diagnosis of resectable PC at early stages. Several clinical studies have indicated that the detection and surgery of small resectable PC (<1?cm) can significantly improve survival; however, imaging diagnosis and accurate resection of small PC remain challenging. Here, we report the feasibility of "immuno-OpenPET" as a novel approach enabling not only early diagnosis but also image-guided surgery, using a small (<1?cm) resectable PC orthotopic xenograft mouse model. For immuno-OpenPET, we utilized our original OpenPET system, which enables high-resolution positron emission tomography (PET) imaging with depth-of-interaction detectors, as well as real-time image-guided surgery, by arranging the detectors to create an open space for surgery and accelerating the image reconstruction process by graphics processing units. For immuno-OpenPET, 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab was intraperitoneally administered into mice. It clearly identified PC tumors ?3?mm. In contrast, neither OpenPET with intravenous-administered 64Cu-cetuximab nor intraperitoneal/intravenous-administered 18F-FDG (a traditional PET probe) could detect PC in this model. Immuno-OpenPET-guided surgery accurately resected small PC in mice and achieved significantly prolonged survival. This technology could provide a novel diagnostic and therapeutic strategy for small resectable PC to improve patient survival.
Project description:The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68-0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82-1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71-0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.
Project description:A sensitive assay to identify biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. In this study, we have conducted a prospective sample collection and retrospective blinded validation (PRoBE design) to evaluate the performance and translational utilities of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. The Affymetrix HG U133 Plus 2.0 Array and 2D-DIGE were used to profile transcriptomes and proteomes in saliva supernatants respectively. Significant variations of salivary transcriptomic and proteomic profiles were observed between breast cancer patients and healthy controls. Eleven transcriptomic biomarker candidates and two proteomic biomarker candidates were selected for a preclinical validation using an independent sample set. Transcriptomic biomarkers were validated by RT-qPCR and proteomic biomarkers were validated by quantitative protein immunoblot. Eight mRNA biomarkers and one protein biomarker have been validated for breast cancer detection, yielding ROC-plot AUC values between 0.665 and 0.959. This report provides proof of concept of salivary biomarkers for the non-invasive detection of breast cancer. The salivary biomarkers’ discriminatory power paves the way for a PRoBE-design definitive validation study. Keywords: Salivary biomarker, Breast cancer, Early detection, Salivary transcriptome, Salivary proteome This study, which was approved by the UCLA and Cedars-Sinai Medical Center Institutional Review Boards (#06-07-043 and #3870, respectively), started sample collection in February 2007. The sample collection followed the PRoBE principle (prospective specimen collection). The saliva bank for breast cancer project at the UCLA Dental Research Institute in collaboration with Cedars Sinai Medical Center has collected 200 saliva samples since 2007 with all subjects recruited from the Saul and Joyce Brandman Breast Cancer Center. Of these, 113 samples, including 41 breast cancer patients and 72 healthy control individuals, were selected for the discovery and validation phase of this study. Inclusion criteria of cancer patients consisted of a confirmed diagnosis of breast cancer. Exclusion criteria of cancer patients included therapy/surgery and/or a diagnosis of other malignancies within 5 years prior to saliva collection. Exclusion criteria of control patients included a diagnosis of any malignancies within 5 years prior to saliva collection. Written informed consents and questionnaire data sheets were obtained from all patients who agreed to serve as saliva donors. Unstimulated saliva samples were consistently collected, stabilized, and preserved as previously described. The sample supernatants were reserved at -80 C prior to assay. This study consisted of a discovery phase, followed by an independent preclinical validation phase. Of the 113 samples, 10 breast cancer samples and 10 healthy control samples were chosen for the discovery phase. All breast cancer cases are invasive ductal carcinoma (IDC), the most common type of breast cancer. Biomarkers identified from the discovery studies were first verified using the discovery sample set. An independent sample set, including 31 breast cancer patients and 62 healthy control subjects, was used for the biomarker validation phase.
Project description:This SuperSeries is composed of the following subset Series: GSE24037: Salivary cytokine alterations in HIV infection part 1 GSE24064: Salivary cytokine alterations in HIV infection part 2 Refer to individual Series
Project description:<b>Background: </b>Port catheter (PC) is a classical route of administering chemotherapy for breast cancer patients. We established a standard operating procedure (SOP) of intraoperative ipsilateral subclavian PC implantation in selected resectable breast cancer patients.<br><br><b>Methods: </b>We conducted a prospective clinical study to assess its safety and complications. A total of seventy six resectable breast cancer patients were included for intraoperative ipsilateral subclavian PC implantation. Thirty patients receiving conventional percutaneous contralateral PC implantation under local anesthesia at the same period were recruited as control group. The time consuming of implantation, and PC-related complications were recorded. Visual analog scale questionnaires were used to assess patients' satisfaction.<br><br><b>Results: </b>Compared with conventional contralateral PC implantation under local anesthesia, SOP for intraoperative ipsilateral subclavian PC implantation significantly shortens the time consuming (11.6 vs. 28.6 min, p < 0.001). With a median retention time of 6.3 months, the overall incidence rate of PC-related complications is 21%, of which the most common complications are infections and venous thromboembolism (7.9% for each). Most patients (86.8%) with intraoperative ipsilateral subclavian PC implantation have completed the whole chemotherapy successfully. Due to the general anesthesia and shorter time consuming, intraoperative implantation gains significantly more patients' satisfaction.<br><br><b>Conclusions: </b>In the present study, we develop a SOP for intraoperative ipsilateral subclavian PC implantation in resectable breast cancer patients, which is noval, convenient, and safe. In selected breast cancer patients with indications for adjuvant chemotherapy, this practice could significantly shorten the time consuming of PC implantation and improve the degree of patients' satisfaction.
Project description:Lipid remodeling is crucial for hypoxic tolerance in animals, whilst little is known about the hypoxia-induced lipid dynamics in plant cells. Here we performed a mass spectrometry-based analysis to survey the lipid profiles of Arabidopsis rosettes under various hypoxic conditions. We observed that hypoxia caused a significant increase in total amounts of phosphatidylserine, phosphatidic acid and oxylipins, but a decrease in phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Particularly, significant gains in the polyunsaturated species of PC, PE and phosphatidylinositol, and losses in their saturated and mono-unsaturated species were evident during hypoxia. Moreover, hypoxia led to a remarkable elevation of ceramides and hydroxyceramides. Depletion of ceramide synthases LOH1, LOH2, and LOH3 enhanced plant sensitivity to dark submergence (DS), but displayed more resistance to submergence under light than wild type. Consistently, levels of unsaturated ceramide species (22:1, 24:1, and 26:1) predominantly declined in the loh1, loh2, and loh3 mutants under DS. Evidence that C24:1-ceramide interacted with recombinant CTR1 protein in vitro, enhanced ER-to-nucleus translocation of EIN2-GFP and stabilization of EIN3-GFP in vivo, suggests a role of ceramides in modulating ethylene signaling. The DS-sensitive phenotypes of loh mutants were rescued by a ctr1-1 mutation. Thus, our findings demonstrate that unsaturation of very-long-chain ceramides is a protective strategy for hypoxic tolerance in Arabidopsis. Arabidopsis Affymetrix GeneChip arrays were probed with RNAs isolated from leaves of untreated plants (controls) and plants upon hypoxia under light submergence for 48 h.