scholarly journals Overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues predicts poor survival in pancreatic ductal adenocarcinoma

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Shu Dong ◽  
Fei Huang ◽  
Hao Zhang ◽  
Qiwen Chen
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Gene Expression Omnibus ◽  
Ductal Adenocarcinoma ◽  
Advanced Tumor Stage ◽  
Kaplan Meier ◽  
Advanced Tumor ◽  
Tumor Tissues

AbstractOverexpressed genes in tumors usually contributed to aggressiveness in pancreatic ductal adenocarcinoma (PDAC). Using Gene Expression Omnibus (GEO) profiles including GSE46234, GSE71989, and GSE107610, we detected overexpressed genes in tumors with R program, which were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO), and Reactome pathway databases. Then, we performed a survival analysis of enriched genes based on TCGA profile. Our results revealed that high BUB1B, CCNA2, CDC20, and CDK1 expression in tumors was significantly associated with worse overall survival (OS) (Log rank P=0.00338, P=0.0447, P=0.00965, and P=0.00479, respectively), which was validated using a Kaplan–Meier plotter with a median cutoff (Log rank P=0.028, P=0.0035, P=0.039, and P=0.0033, respectively). Moreover, overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues was significantly associated with disease-free survival (DFS) in PDAC patients (Log rank P=0.00565, P=0.0357, P=0.00104, and P=0.00121, respectively). BUB1B, CCNA2, CDC20, and CDK1 were significantly overexpressed in deceased PDAC patients (all P<0.01) and in patients with recurrence/disease progression (all P<0.05). In addition, PDAC patients with neoplasms of histologic grade G3-4 had significantly higher BUB1B, CCNA2 and CDC20 levels (all P<0.05). In conclusion, the up-regulation of BUB1B, CCNA2, CDC20, CDK1, and WEE1 in tumor tissues are associated with worse OS and DFS in PDAC and is correlated with advanced tumor stage and tumor development.

Elevated expression of ASF1B correlates with poor prognosis in human lung adenocarcinoma

2021 ◽  
Vol 18 (2) ◽  
pp. 115-127
Author(s):  
Zhenxing Feng ◽  
Jiao Zhang ◽  
Yafang Zheng ◽  
Qingzhang Wang ◽  
Xiaochuan Min ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Tumor Development ◽  
Tumor Stage ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Advanced Tumor Stage ◽  
Aberrant Expression ◽  
Free Survival ◽  
Advanced Tumor

Aim: ASF1 is involved in tumorigenesis. However, its possible role in lung adenocarcinoma (LUAD) is unclear. This study thus explored the role of ASF1A and ASF1B in LUAD. Materials & methods: Data from The Cancer Genome Atlas and Gene Expression Omnibus were employed to investigate ASF1A and ASF1B expression and its roles in LUAD prognosis. Immunohistochemistry was applied to determine the protein expression of ASF1B of 30 LUAD patients. Results: The upregulation of ASF1B in tumor tissues is associated with worse overall survival and progress-free survival and is correlated with advanced tumor stage and tumor development. However, aberrant expression of ASF1A was not found in LUAD and ASF1A was not related to patients’ overall survival and progress-free survival. Conclusion: ASF1B could be a promising prognostic and therapeutic biomarker in LUAD.

Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer

2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Perioperative Morbidity ◽  
Log Rank Test ◽  
Kaplan Meier

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.

scholarly journals Prognostic Significance of Preoperative and Postoperative Complement C3 Depletion in Gastric Cancer: A Three-Year Survival Investigation

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jinning Ye ◽  
Yufeng Ren ◽  
Jianhui Chen ◽  
Wu Song ◽  
Chuangqi Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Hospital Costs ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Complement C3 ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Prolonged Hospital

Objectives. The role of complement system in predicting prognosis of gastric cancer (GC) remains obscured. This study aims to explore the incidence of complement C3 depletion and associated outcomes in GC patients. Methods. between August 2013 and December 2013, 106 patients with gastric adenocarcinoma were prospectively analyzed. Plasma levels of complement C3 and C4 were detected at baseline, one day before surgery, and postoperative day 3, respectively. Patients with low C3 levels (<0.75 mg/mL) were considered as having complement depletion (CD), while others with normal C3 levels were included as control. The 3-year overall survival (OS), disease-free survival (DFS), and other outcomes were compared between both groups, with the CD incidence explored meanwhile. Results. The CD incidence was 28.3% before surgery but increased to 37.7% after surgery. Preoperative CD was related to prolonged hospital stay (22.7 versus 19.2 day, P=0.032) and increased postoperative complications (33.3% versus 14.5%, P=0.030) and hospital costs (P=0.013). Besides, postoperative C3 depletion was significantly associated with decreased 3-year OS (P=0.022) and DFS (P=0.003). Moreover, postoperative C3 depletion and advanced tumor stage were independent predictive factors of poor prognosis. Conclusions. Complement C3 depletion occurring in gastric cancer was associated with poor short-term and long-term outcomes.

scholarly journals Aberrant cytoplasmic localization of ARID1B activates ERK signaling and promotes oncogenesis

2020 ◽  
pp. jcs.251637
Author(s):  
Srinivas Animireddy ◽  
Padmavathi Kavadipula ◽  
Viswakalyan Kotapalli ◽  
Swarnalata Gowrishankar ◽  
Satish Rao ◽  
...  
Keyword(s):  
Pancreatic Tumor ◽  
Tumor Stage ◽  
Erk Signaling ◽  
Advanced Tumor Stage ◽  
Cytoplasmic Localization ◽  
Advanced Tumor ◽  
Tumor Tissues ◽  
Localization Signal ◽  
Intracellular Fluorescence ◽  
Oncogenic Function

The ARID1B/BAF250b subunit of the human SWI/SNF chromatin remodeling complex is a canonical nuclear tumor suppressor. We employed in silico prediction, intracellular fluorescence and cellular fractionation based subcellular localization analyses to identify the ARID1B nuclear localization signal. A cytoplasm-restricted ARID1B-NLS mutant was significantly compromised in its canonical transcription activation and tumor suppressive functions, as expected. Surprisingly however, cytoplasmic localization appeared to induce a gain of oncogenic function in ARID1B as evidenced from several cell line and mouse xenograft based assays. Mechanistically, cytoplasm-localized ARID1B could bind c-RAF and PPP1CA causing stimulation of RAF-ERK signaling and β-catenin transcription activity. ARID1B harboring NLS mutations derived from tumor samples also exhibited aberrant cytoplasmic localization and acquired a neo-morphic oncogenic function via activation of RAF-ERK signaling. Further, immunohistochemistry on a tissue microarray revealed significant correlation of ARID1B cytoplasmic localization with increased levels of active forms of ERK1/2 and β-catenin as well as with advanced tumor stage and lymph node positivity in human primary pancreatic tumor tissues. ARID1B therefore promotes oncogenesis through cytoplasm-based gain of function mechanisms in addition to dysregulation in the nucleus.

ΔTAp73 Upregulation Correlates With Poor Prognosis in Human Tumors: Putative In Vivo Network Involving p73 Isoforms, p53, and E2F-1

2006 ◽  
Vol 24 (5) ◽  
pp. 805-815 ◽  
Author(s):  
Gemma Domínguez ◽  
José M. García ◽  
Cristina Peña ◽  
Javier Silva ◽  
Vanesa García ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Cell Transformation ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Breast Cancer Patients ◽  
Oncogenic Ras ◽  
Advanced Tumor ◽  
Tumor Tissues ◽  
Ras Status

Purpose Although full-length TAp73 variants largely mimic p53 suppressor activities, the transactivation-deficient transcripts ΔTAp73 exert an oncogenic effect by inactivating p53 and TAp73 suppressor properties. Additionally, ΔTAp73 may cooperate with oncogenic RAS to induce cell transformation, confer drug resistance, and induce the phosphorylation of phosphorylated Rb. Here, we study the expression of TAp73 and ΔTAp73 variants and assess possible associations with E2F-1, p53 and K-ras status. We address the possible clinical relevance of alterations in these genes. Patients and Methods We determine in 113 colon and 60 breast cancer patients (a) the expression levels of TAp73, ΔTAp73 (ΔEx2p73, ΔEx2/3p73, and ΔNp73), and E2F-1 transcripts by quantitative real-time reverse transcriptase polymerase chain reaction (PCR); (b) mutations in the first exon of K-ras by PCR–single-stranded confirmational polymorphism; and (c) p53 status by immunohistochemistry. Tumor characteristics were examined in each patient. Results Both suppressor and oncogenic isoforms of TP73 were significantly coupregulated in tumor tissues. Associations were observed between (a) p53 wild type status and upregulation of some TP73 variants; (b) overexpression of E2F-1 and some TP73 forms; and (c) upregulation of ΔTAp73 variants and advanced pathologic stage, lymph node metastasis, vascular invasion, presence of polyps, and tumor localization. Conclusion Overexpression of TP73 variants in tumor tissues indicates that they may be involved in colon and breast carcinogenesis. The association between upregulation of ΔTAp73 isoforms and poor prognosis features, specifically advanced tumor stage, suggests that they may be of practical clinical prognostic value. Interestingly, the in vivo associations identified here may indicate a functional network involving p73 variants, p53, and E2F-1.

scholarly journals Overexpressed Proteins in HCC Cell-Derived Exosomes, CCT8, and Cofilin-1 Are Potential Biomarkers for Patients with HCC

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1221
Author(s):  
Hyo Jung Cho ◽  
Geum Ok Baek ◽  
Moon Gyeong Yoon ◽  
Hye Ri Ahn ◽  
Ju A Son ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Serum Markers ◽  
Advanced Tumor Stage ◽  
Protein Markers ◽  
Poor Overall Survival ◽  
Advanced Tumor ◽  
Normal Hepatocyte ◽  
Potential Biomarkers

Protein markers of hepatocellular carcinoma (HCC)-derived exosomes (HEX) have not yet been fully evaluated. Here, we identified novel protein contents of HEX and their clinical significance as biomarkers. Exosomes were isolated from human HCC cell lines and an immortalized normal hepatocyte cell line. Proteomic analyses revealed 15 markedly overexpressed proteins in HEX. The clinical relevance of the 15 proteins was analyzed in public RNA-sequencing datasets, and 6 proteins were selected as candidate of potential biomarkers. Serum CCT8 and CFL1 were markedly overexpressed in test cohort (n = 8). In the validation cohort (n = 224), the area under the curve (AUC) of serum CCT8 and CFL1 for HCC diagnosis was calculated as 0.698 and 0.677, respectively, whereas that of serum alpha-fetoprotein (AFP) was 0.628. The combination of three serum markers (CCT8, CFL1, and AFP) demonstrated the highest AUC for HCC diagnosis. (AUC = 0.838, 95% confidence interval = 0.773–0.876) Furthermore, higher serum CCT8 and CFL1 concentrations were significantly associated with the presence of vascular invasion, advanced tumor stage, poor disease-free survival, and poor overall survival. Cofilin-1 and CCT8, enriched proteins in HEX, were identified as potential diagnostic and prognostic serum biomarkers for HCC patients.

scholarly journals KRAS drives immune evasion in a genetic model of pancreatic cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Irene Ischenko ◽  
Stephen D’Amico ◽  
Manisha Rao ◽  
Jinyu Li ◽  
Michael J. Hayman ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Immune Evasion ◽  
Genetic Model ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
Host Immune System ◽  
Advanced Tumor Stage ◽  
Immunodeficient Mice ◽  
Advanced Tumor ◽  
Underlying Causes

AbstractImmune evasion is a hallmark of KRAS-driven cancers, but the underlying causes remain unresolved. Here, we use a mouse model of pancreatic ductal adenocarcinoma to inactivate KRAS by CRISPR-mediated genome editing. We demonstrate that at an advanced tumor stage, dependence on KRAS for tumor growth is reduced and is manifested in the suppression of antitumor immunity. KRAS-deficient cells retain the ability to form tumors in immunodeficient mice. However, they fail to evade the host immune system in syngeneic wild-type mice, triggering strong antitumor response. We uncover changes both in tumor cells and host immune cells attributable to oncogenic KRAS expression. We identify BRAF and MYC as key mediators of KRAS-driven tumor immune suppression and show that loss of BRAF effectively blocks tumor growth in mice. Applying our results to human PDAC we show that lowering KRAS activity is likewise associated with a more vigorous immune environment.

scholarly journals Identification of Prognostic and Therapeutic Biomarkers among FAM83 Family Members for Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Zuyi Ma ◽  
Zixuan Zhou ◽  
Hongkai Zhuang ◽  
Zhenchong Li ◽  
Zuguang Ma ◽  
...  
Keyword(s):  
T Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Value ◽  
Immune Cell ◽  
Sequence Similarity ◽  
Cell Infiltration ◽  
Ductal Adenocarcinoma ◽  
Advanced Tumor Stage ◽  
Mhc Molecules ◽  
Advanced Tumor

Family with sequence similarity 83 (FAM83) members were shown recently to have oncogenic effect in a variety of cancer types, but the biological roles and prognostic value of FAM83 family in pancreatic ductal adenocarcinoma remain unknown. In the current study, the clinical significance and molecular function of the FAM83 family were assessed by multiple bioinformatics analysis. Besides, potential associations between differentially expressed genes (DEGs) of FAM83 family and antitumor immunity were evaluated using TIMER and TISIDB analyses. As the results show, FAM83A, FAM83D, FAM83E, and FAM83H were significantly upregulated in PDAC and were identified as DEGs. Higher expression of FAM83A, FAM83B, FAM83D, FAM83E, and FAM83H were associated with advanced tumor stage or worse patient prognosis. Importantly, the overexpression of DEGs was found to be significantly correlated with activated KRAS and loss of SMAD4, which are important drivers for PDAC. Further, FAM83A, FAM83D, and FAM83H were associated with CD8+ T cell, Gamma Delta T cell, and CD4+ T cell infiltration in PDAC and FAM83H was found closely correlated with some immunomodulators including immunoinhibitors, immunostimulators, and MHC molecules. In conclusion, FAM83A, FAM83D, FAM83E, and FAM83H have significant prognostic value in PDAC and they may play important roles in regulating tumor progression and the immune cell infiltration.

Prognostic influence of waiting time in management of pancreatic ductal adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15726-e15726
Author(s):  
Rei Suzuki ◽  
Tadayuki Takagi ◽  
Takuto Hikichi ◽  
Hiromasa Ohira
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Surgical Resection ◽  
Waiting Time ◽  
Waiting Times ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
Survival Group ◽  
Long Survival

e15726 Background: Since pancreatic ductal adenocarcinoma (PDAC) showed aggressive progression, we hypothesized that waiting time in management might have prognostic influence on patients’ prognosis. Methods: Data on PDAC patients who underwent either chemotherapy or surgical resection in our hospital (2006 – 2016) were collected. Waiting time was classified into two groups as detection-to-diagnosis waiting time (WT1) and diagnosis-to-treatment waiting time (WT2). Median disease free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method and utilized as cut-off points to divide patients into 2 groups (short- and long-survival group). Clinical characteristics including age, sex, tumor size, location of tumor, stage of disease, the levels of serum tumor markers, waiting times, use of adjuvant chemotherapy and resectability were compared between the two survival groups. Results: In total, 149 patients were included. Seventy-two patients who underwent chemotherapy (median OS: 9.7 months) were divided into long survival group (n = 42) and short survival group (n = 30). We did not find significant differences in both WT1 (20.0 days vs. 19.0 days, P = 0.98) and WT2 (17.0 days vs. 18.5 days, P = 0.93), while proportion of patients with locally advanced disease ( P = 0.02) and combination chemotherapy ( P = 0.003) was significantly associated with long survival. Among 79 patients underwent surgical resection, median DFS after pancreatic resection was 16.4 months and OS was 35.0 months. The patients were divided into short DFS (n = 47) versus long DFS (n = 30) and short OS (n = 57) versus long OS (n = 20). We did not find significant differences in both WT1 (short vs. long DFS: 21.0 days vs. 21.0 day, P = 0.65, short vs. long OS: 21.0 days vs. 23.0 days, P = 0.45) and WT2 (short vs. long DFS: 46.0 days vs. 44.5 days, P = 0.45, short vs. long OS: 46.0 vs. 41.0 days, P = 0.36). Both advanced T- and N-stage was significantly associated with poor DFS ( P = 0.049, P = 0.03, respectively) while only advanced T-stage was significantly associated with poor OS ( P = 0.02). Conclusions: Our findings suggested that both detection-to-diagnosis waiting time and diagnosis-to-treatment waiting time might not influence on prognosis of patients with PDAC.

scholarly journals The predictive value of lncRNA MIR31HG expression on clinical outcomes in patients with solid malignant tumors

2020 ◽  
Author(s):  
Chao Tu ◽  
Xiaolei Ren ◽  
Jieyu He ◽  
Shuangqing Li ◽  
Lin Qi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcomes ◽  
Gastrointestinal Cancer ◽  
Prognostic Value ◽  
Malignant Tumors ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Tcga Dataset

Abstract Background Emerging studies have explored the prognostic value of MIR31HG in cancers, but its role remains elusive. Herein, we aimed to summarize the prognostic potential of MIR31HG in this study. Methods Several databases were searched for literature retrieval on Dec 5, 2019. Overall and subgroup analyses were conducted to measure the relationship between MIR31HG expression and clinical outcomes. Moreover, GEPIA was applied for validation of prognostic value of MIR31HG in tumor patients in TCGA dataset. Results Overall, seventeen studies with 2,573 patients were enrolled. Compared to counterparts, those patients with high MIR31HG expression tended to have shorter RFS. Notably, MIR31HG overexpression predicted unfavorable OS in lung cancer. By contrast, gastrointestinal cancer patients with elevated MIR31HG expression predicted better OS and disease-free survival. Additionally, MIR31HG overexpression was significantly associated with worse clinicopathological features including advanced tumor stage and LNM in lung cancer, but favorable clinical characteristics in gastrointestinal cancer. Moreover, the positive association between MIR31HG and OS in lung cancer was further confirmed in TCGA dataset. Conclusion Overexpression of MIR31HG suggested remarkable association with poor prognosis in terms of OS, tumor stage, and LNM in lung cancer, but favorable prognosis in gastrointestinal cancer. Therefore, MIR31HG may serve as a promising prognostic biomarker in multiple cancers.

Sign in / Sign up

Export Citation Format

Share Document