Novel nanobiosensor based protease biomarkers for early detection and prognosis of pancreatic cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16787-e16787
Author(s):  
Anup Kasi ◽  
James Kaiser Houghton ◽  
Anwaar Saeed ◽  
Stephen K. Williamson ◽  
Obdulia Covarrubias Zambrano ◽  
...  

e16787 Background: Identifying novel biomarkers for early detection and prognosis would allow for improved survival outcomes in pancreatic cancer (PC). Arginase has been implicated in tumorigenesis through its production of L-ornithine. Its aberrant expression provides metabolites for tumor proliferation. Methods: In our study, 47 patients with metastatic PC, 29 with localized PC, and 50 healthy controls were enrolled at KU Cancer Center from 2000 to 2019. Overall survival (OS) was retrospectively assessed and correlated to serum protease levels at diagnosis. Protease expression was analyzed using nanobiosensors, which utilized fluorescent nanoparticles read by Spectra Scan to measure arginase, matrix metalloproteinases (MMPs), urokinase plasminogen activator (uPA), neutrophil elastase (NE), cathepsin B (CTSB), and cathepsin E (CTSE). Survival analysis was completed by Kaplan-Meier method. Results: Protease expression in localized vs. healthy cases was significant for (CTSB [p = 1.33E-10], MMP1 [p = 6.66E-21], MMP3 [p = 1.39E-13], MMP9 [p = 2.77E-08], NE [p = 0.00015], uPA [p = 2.55E-11]) and borderline significant for arginase [p = 0.05082]. Protease expression in metastatic vs. healthy cases was significant for (CTSB [p = 7.06E-06], MMP1 [p = 3.08E-12], MMP3 [p = 2.51E-14], MMP9 [p = 1.73E-08], NE [p = 0.01430], uPA [p = 0.00024]). Further, metastatic vs. localized cancer was significant for (arginase [p = 0.00034], CTSB [p = 0.00584], MMP1 [p = 2.03E-13], NE [p = 2.29E-10], and uPA [p = 6.58E-07]. Characteristics of 21 localized PC patients are illustrated in Table. Median OS was 25m in localized PC with low Arginase expression (mean < 215) vs 17.5m in high Arginase expression (p = 0.0477). Conclusions: Expression pattern of CTSB, MMP, NE, arginase, uPA proteases showed statistical significant difference for detection of localized PC vs metastatic PC vs healthy cases. In localized PC, lower arginase expression showed a statistically significant improvement in survival vs high arginase expression. Arginase expression was borderline significant for detection of localized PC vs healthy controls, likely due to small sample. Arginase as a potential biomarker for early detection and prognosis of PC warrants validation in a larger cohort. [Table: see text]

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2565
Author(s):  
Yixing Wu ◽  
Hongmei Zeng ◽  
Qing Yu ◽  
Huatian Huang ◽  
Beatrice Fervers ◽  
...  

Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I–IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Chumei Huang ◽  
Zhuangjian Ye ◽  
Jianxin Wan ◽  
Jianbo Liang ◽  
Min Liu ◽  
...  

Purpose. Secreted frizzled-related protein 2 (sFRP2) is a secreted protein associated with cancer drug resistance and metastasis. However, few studies have reported serum sFRP2 levels in breast cancer. We evaluated serum sFRP2 as a potential biomarker for breast cancer. Methods. Serum sFRP2 concentrations were detected in 274 breast cancer patients along with 147 normal healthy controls by enzyme-linked immunosorbent assay (ELISA). Diagnostic significance was evaluated by area under the curve (AUC) analysis and the Youden index. Prognostic significance was determined by Kaplan-Meier survival method and univariate and multivariate Cox proportional hazard regression model analyses. Results. Serum sFRP2 was elevated in breast cancer patients compared to normal healthy controls (P<0.001). The sensitivity of sFRP2 in diagnosing breast cancer was 76.9% at a specificity of 76.6%. Elevated serum sFRP2 levels are associated with primary tumor size, TNM stage, and lymph node metastases. The Kaplan-Meier curves showed a significant association of serum sFRP2 with progression-free survival. The multivariate Cox analysis confirmed that high serum sFRP2 was an independent prognostic factor for poor prognosis (HR=3.89, 95% CI=1.95-7.68, P=0.001). Conclusions. In conclusion, serum sFRP2 may serve as a potential biomarker for breast cancer diagnosis and prognostic evaluation.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2932-2932
Author(s):  
Farzana A. Sayani ◽  
Nizar J. Bahlis ◽  
Peter Faris ◽  
Mary Lynn Savoie ◽  
Ahsan Chaudhry ◽  
...  

Abstract Multiple dose intensive chemotherapy regimens have been used for induction/mobilization of stem cells for autologous stem cell transplantation (ASCT) in multiple myeloma. However, the exact role and regimens of such dose intensive chemotherapy has not been clearly defined. We therefore did a retrospective study to determine if dose intensive cyclophosphamide (Cyclo) 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in improved relapse rate and survival compared to standard mobilization with only Cyclo 2 g/m2. Between January 1998 and March 2004, a consecutive series of 57 newly diagnosed multiple myeloma patients receiving DICEP (38) or Cyclo (19) for in-vivo purging/mobilization were analyzed. Both groups were similar in regards to age and sex. There were no significant differences in IPI score, Durie-Salmon stage, B2 microglobulin, calcium, creatinine and albumin levels between treatment groups. Outcomes included time to relapse and time to death. Median follow up time was 799 days. Kaplan-Meier plots for time to relapse showed no significant difference (p=0.0992). Median relapse time in the DICEP group was 905 days (95% CI 580–1604) compared to 1112 days (95% CI 742-infinity) in the Cyclo group. Kaplan-Meier plots for overall survival showed no significant difference between both groups (p=0.8664). The median survival times have not yet been reached in either group and are not reported. Analysis revealed no discernable confounding risk factors. Effects of treatment on outcomes were not altered after adjusting for IPI score and Durie-Salmon staging using the stratified log-rank test. Small sample size and short duration of followup are potential limiting factors for this study, however, preliminary analysis of a larger sample of 91 multiple myeloma patients receiving either DICEP or a less intense induction/mobilization regimen, also revealed no significant difference in disease free or overall survival. Monoclonal plasma cell contamination of stem cell products was not significantly different between both groups (DICEP 42.9%, Cyclo 56.3%, p=0.5573). This study therefore suggests that the very intense DICEP induction/mobilization regimen results in no significant difference in survival outcomes. The more intense regimen does not significantly decrease tumor contamination of autograft stem cells. Overall, our experience suggests that novel induction therapies such as bortezomib, lenolidomide etc. should be pursued in preference to any further study of high dose cytotoxic chemotherapy induction. Figure Figure


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 708-708
Author(s):  
Parisa Momtaz ◽  
Catherine Anne O'Connor ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
Kenneth H. Yu ◽  
...  

708 Background: Given encouraging responses of platinum agents and poly-ADP ribose polymerase inhibitors (PARPi) in BRCA mutated (mut) PDAC, we sought to identify patients (pts) with BRCA mut PDAC treated at MSKCC and to evaluate outcome. Methods: Institutional database at MSK with IRB approval was queried for PDAC germline (g) or somatic (s) BRCA1/2 mut. Genomic profiling, clinicopathologic characteristics and outcomes were collected. Overall survival (OS) from diagnosis was estimated using Kaplan-Meier method. Results: n = 126 with BRCA1/2 mut PDAC were identified between 1/2011-12/2018. n = 77 (61%) male and median age of 62 (range 24-85) at diagnosis. n = 78 (62%) had g BRCA mut (n = 21 BRCA1; n = 57 BRCA2). n = 54 (43%) had a family history of BRCA-related malignancies; 35pts (28%) with a personal history of other BRCA-associated malignancy. n = 66 (52%) AJCC stage IV; of these 43pts (65%) received platinum-based therapy with a partial response (PR) in 35pts (81%); median duration 7 months (m) (range 0.5-39m). n = 40 (32%) received ≥ 4 lines of therapy (range 1-6 lines). n = 44 (35%) received PARPi and 11% (n = 14) received immunotherapy. Median OS for the entire cohort 32.1 m (95% CI 23.9, 42.6). Median OS for stage I-II 49.9m (95% CI 38.5,-); stage III 43m (95% CI 33.9,-) and stage IV 19.1m (95% CI 19.1 16.1,25.8). We did not observe a statistically significant difference in OS between BRCA1 vs BRCA2 pts. Conclusions: BRCA mut PDAC constitutes a small but likely distinct biologic subgroup. Improved OS was notable relative to historical data, possibly due to the integration of platinum and PARPi therapy and possibly due to contribution from disease biology. [Table: see text]


2017 ◽  
Vol 27 (2) ◽  
pp. 339-343 ◽  
Author(s):  
Ping Sun ◽  
Yong Shen ◽  
Jiao-Mei Gong ◽  
Li-Li Zhou ◽  
Jia-He Sheng ◽  
...  

BackgroundCervical cancer is the second most common cancer among women worldwide. The potential of microRNAs as novel biomarkers in cervical cancer is growing.ObjectivesIn this study, we investigated the functions and targets of miR-466 in cervical cancer tissues.MethodsFresh cervical tissues were obtained from 157 patients with cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy controls, and the tissues were immediately frozen in liquid nitrogen until use. The RNA was extracted and quantitative real-time polymerase chain reaction (PCR) was performed.ResultsA total of 157 participants were summarized, including 56 patients with cervical cancer, 60 patients with CIN, and 49 healthy controls. The expression levels of miR-466 in cervical cancers (0.68) were higher than that in healthy controls (0.082) (P < 0.01). The average fold changes of miR-466 in the patients with CIN group and people group were 0.28 and 0.082, respectively (P < 0.01). It was a statistically significant difference in patients with lymph node involvement (P = 0.022). However, the expression of miR-466 was not correlated with International Federation of Gynecology and Obstetrics stages, tumor size, or vascular invasion (P = 0.506, P = 0.667, and P = 0.108, respectively).ConclusionsOur results indicate that the aberrant expression of miR-466 is closely associated with the occurrence and development of cervical cancer.


2021 ◽  
Author(s):  
Weijiang Hu ◽  
Jingbo Zhang ◽  
Kai Liu ◽  
Jie Liu ◽  
Yuxin Zheng ◽  
...  

Abstract The overwhelming majority of subjects in current silicosis mRNA and miRNA expression profile are of human blood, lung cell, or rats model, which put limit on understanding of silicosis pathogenesis and therapy. It is essential to identify differentially expressed mRNAs and miRNAs profiles in silicosis patients lung tissues, and explore potential biomarker for early detection of silicosis. So we conducted a transcriptome study based on fifteen silicosis patients and eight normal people lung tissues, meanwhile, we validated the predictions with 404 silicosis patients and 177 normal people blood samples. The results showed that 1417 and 241 differentially expressed mRNAs and miRNAs were identified, respectively, among normal people, early stage silicosis, and advanced silicosis lung tissues (all P values < 0.05), whereas there were no significant difference in most mRNAs or miRNAs expression between early stage and advanced stage silicosis lung tissues. Enrichment analysis indicated phagosome, ribosome, olfactory transduction, antigen processing and presentation and PI3K-Akt pathways were mainly involved in the onset of silicosis. Series test of cluster (STC) analysis segregated differentially expressed mRNAs and miRNAs into five and three expressopm profiles patterns, repectively, with significant trends (P < 0.05), meanwhile, ten mRNAs (PIK3R3, KRAS, CTNNB1, HIF1A, ITGA2, KIT, SOCS3, GNAI3, STAT3 and PTEN) and nine miRNAs (hsa-miR-27a-3p, hsa-miR-27b-3p, hsa-miR-34b-3p, hsa-miR-3613-3p, hsa-miR-575, hsa-miR-8063, hsa-miR-937-5p, hsa-miR-181a-5p and hsa-miR-181b-5p) in patterns with opposite trends were selected to make further RT-qPCR validation in lung tissues and blood samples. Finally, the lung tissues RT-qPCR results verified microarray analyses of mRNAs and miRNAs expression trends, except for hsa-miR-575, hsa-miR-8063, and hsa-miR-937-5p, whereas blood samples RT-qPCR results PTEN and GNAI3 had opposite expression trends to those of lung tissues, and PTEN was identified as potential biomarker for silicosis early detection due to low methylation in the blood.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4046-4046 ◽  
Author(s):  
Megan Greally ◽  
Vivian E. Strong ◽  
Sam S. Yoon ◽  
Daniel G. Coit ◽  
Joanne F Chou ◽  
...  

4046 Background: Peri-op chemo (ctx) and surgery is a standard in the treatment of GC, based on the MAGIC (NEJM 2006; 355:11) and FLOT4 (J Clin Oncol 35:4004 [abstr]) studies. However, less than half of patients (pts) completed ctx in the MAGIC and FLOT4 studies, mainly from issues delivering post-op therapy. We assessed safety and feasibility of TNT, where all ctx is given pre-op. Methods: We reviewed GC pts who received TNT or peri-op ctx and had surgery; decision for TNT was by physician preference, based on clinical or radiographic benefit to justify completing ctx pre-op. Pt characteristics were compared using Fisher’s exact and Wilcoxon Rank Sum tests. Post-op length of stay (LOS) was calculated from date of surgery (DOS) to date of discharge and surgical morbidity was determined using the Clavien-Dindo classification. Progression free survival (PFS) and overall survival (OS) were calculated from DOS using Kaplan-Meier methods and compared between groups using the log-rank test. Results: 120 pts were identified, median age 63, 62.5% male, 98% ECOG 0/1. 93 pts (77.5%) received peri-op ctx and 27 (22.5%) received TNT. In peri-op pts, 19%, 43% and 38% received FLOT, platinum/fluropyrimidine (FP) and ECF/EOX respectively. In TNT pts, 56%, 37% and 7% received FLOT, platinum/FP and ECF/EOX respectively. 57% had subtotal gastrectomy. Surgical outcomes were similar between groups; median LOS was 6 and 7 days (p = 0.31) in peri-op and TNT pts respectively. There was no significant difference in Clavien Dindo grade I-II or III-IV morbidity between groups (p = 0.103). There were no deaths. TNT pts received higher proportions of planned treatment than peri-op ctx pts: 90% vs. 60% FP (0.001); 85% vs. 41% platinum ( < 0.001); 100% vs. 9% epirubicin (0.015) and 53% vs. 28% docetaxel (p = 0.169). At median follow-up of 19 months, median PFS and OS were not reached. There was no significant difference in PFS (p = 0.089) or OS (p = 0.59) between groups. Conclusions: TNT appears safe with no increase in post-op LOS or surgical morbidity observed. TNT pts had higher percentage drug delivery, suggesting potential benefit for administering all ctx before surgery. While longer survival follow-up is required, TNT may be considered in pts with locally advanced GC who are candidates for ctx.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17049-e17049
Author(s):  
Katherine Emilie Rhoades Smith ◽  
Limeng Wan ◽  
Yuan Liu ◽  
Jacqueline T Brown ◽  
Greta Russler ◽  
...  

e17049 Background: There is limited biomarker data available for metastatic hormone sensitive prostate cancer (mHSPC). Inflammatory markers found on routine clinical lab data, including leukocyte to lymphocyte ratios calculated from complete blood counts (CBC), is associated with clinical outcomes (CO) in different malignancies. We investigated the association between basophil-to-lymphocyte ratio (BLR) and CO in a racially diverse patient population with mHSPC. Methods: We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014 – 2020). Demographics, disease characteristics, and laboratory data were collected at the start of upfront therapy with either docetaxel (DOC) or abiraterone (ABI). Overall survival (OS) and progression-free survival (PFS) were used to measure CO. Results: Included were 165 patients with mHSPC with a median follow-up time of 22.6 months. 89 (53.9%) were Black and 76 (46.1%) were Non-Black (White, Asian, or Hispanic). 106 (63%) had Gleason scores of 8-10 and 105 (63.6%) were classified as high-volume disease (per CHAARTED trial criteria). 92 (55.8%) received DOC and 73 (44.2%) received ABI. Worse CO were associated with high BLR at an optimal cut of 0.0265 (range 0 – 0.81 , mean of 0.03, standard deviation 0.09). Elevated BLR is associated with decreased OS (HR 3.51, 1.79 – 6.91, p <0.001) and PFS (HR 1.85, 1.14 – 3.00, p 0.013) in multivariable analyses (MVA). High BLR and low BLR groups were similar except for age as a continuous variable, which was associated with high BLR. Otherwise, there were no significant difference for all reported clinical characteristics, including drug (DOC vs ABI), race (Black vs Non-Black), Gleason, disease volume (per CHARRTED criteria), ECOG, or BMI. Conclusions: In mHSPC, high baseline BLR is associated with worse OS and PFS. Our results are the first to identify that BLR is associated with CO in mHSPC. Further study is needed to validate BLR as a potential biomarker.[Table: see text]


2021 ◽  
Vol 12 ◽  
Author(s):  
Chai Lee Seo ◽  
Jin Young Park ◽  
Jaesub Park ◽  
Hesun Erin Kim ◽  
Jaehwa Cho ◽  
...  

Background: Recognition and early detection of delirium in the intensive care unit (ICU) is essential to improve ICU outcomes. To date, neutrophil-lymphocyte ratio (NLR), one of inflammatory markers, has been proposed as a potential biomarker for brain disorders related to neuroinflammation. This study aimed to investigate whether NLR could be utilized in early detection of delirium in the ICU.Methods: Of 10,144 patients who admitted to the ICU, 1,112 delirium patients (DE) were included in the current study. To compare among inflammatory markers, NLR, C-reactive protein (CRP), and white blood cell (WBC) counts were obtained: the mean NLR, CRP levels, and WBC counts between the initial day of ICU admission and the day of initial delirium onset within DE were examined. The inflammatory marker of 1,272 non-delirium patients (ND) were also comparatively measured as a supplement. Further comparisons included a subgroup analysis based on delirium subtypes (non-hypoactive vs. hypoactive) or admission types (elective vs. emergent).Results: The NLR and CRP levels in DE increased on the day of delirium onset compared to the initial admission day. ND also showed increased CRP levels on the sixth day (the closest day to average delirium onset day among DE) of ICU admission compared to baseline, while NLR in ND did not show significant difference over time. In further analyses, the CRP level of the non-hypoactive group was more increased than that of the hypoactive group during the delirium onset. NLR, however, was more significantly increased in patients with elective admission than in those with emergent admission.Conclusion: Elevation of NLR was more closely linked to the onset of delirium compared to other inflammatory markers, indicating that NLR may play a role in early detection of delirium.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14201-e14201
Author(s):  
Ranga Raman Ganta ◽  
Srividya Nasaka

e14201 Background: Inflammatory response exacerbates mechanisms linked to tumor growth and dissemination. As an index of systemic inflammatory marker, neutrophil lymphocyte ratio (NLR) may be a predictive biomarker of both prognosis and outcome in several malignancies. However very few reports have addressed the association of change in NLR and outcome in operable breast cancer. We evaluated preoperative NLR and postoperative NLR to assess which one would be predictive of disease outcome in triple negative breast cancer patients. Methods: This study included 67 stage I-III triple negative breast cancer patients diagnosed at HCG Cancer center, between 2013 to 2015. Those patients who underwent upfront surgery were included in the study. Patients who received neoadjuvant chemotherapy and those without adequate medical records were excluded. The NLR was calculated from the differential count by dividing neutrophil percentage with lymphocyte percentage. All preoperative NLRs were calculated from medical records, at the first visit. Postoperative NLR was obtained before first cycle chemotherapy. The NLR was divided into high if ratio is > 3 and low if it is ≤ 3. We evaluated prognostic value of NLR on 3 year DFS. Results: The median preoperative NLR was 2.52 (Range 0.77-8.6). The pre op NLR was high in 19 patients (28%) and low in 48 patients (72%). There was no significant difference between two groups in baseline characteristics. Among the preoperative High and low NLR groups, 3 year DFS is statistically significant. The median postoperative NLR was 2.23 (Range 0.89-8.1). The post operative NLR was high in 7 patients (11%) and low in 60 patients (89%). Among the postoperative High and low NLR groups, 3 year DFS is statistically not significant. The 12 (63%) patients in the high preoperative NLR patients were converted to of the low NLR after surgery. Conclusions: Preoperative NLR correlated with outcome in operable triple negative breast cancer than postoperative NLR. The NLR kinetics might be an index of response to the treatment which needs to be evaluated in prospective studies. Drawbacks of the study: single centre, retrospective study and small sample size.[Table: see text][Table: see text]


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