HMGA1 correlates with advanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma

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.

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Stromal hyaluronan accumulation is associated with low tumor grade and nodal metastases in pancreatic ductal adenocarcinoma

Human Pathology ◽

10.1016/j.humpath.2019.05.004 ◽

2019 ◽

Vol 90 ◽

pp. 37-44 ◽

Cited By ~ 1

Author(s):

Brent K. Larson ◽

Michelle Guan ◽

Veronica Placencio ◽

Richard Tuli ◽

Andrew E. Hendifar

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Tumor Grade ◽

Ductal Adenocarcinoma ◽

Nodal Metastases

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Histologic Tumor Grade and Preoperative Bilary Drainage are the Unique Independent Prognostic Factors of Survival in Pancreatic Ductal Adenocarcinoma Patients After Pancreaticoduodenectomy

Journal of Clinical Gastroenterology ◽

10.1097/mcg.0000000000000793 ◽

2018 ◽

Vol 52 (2) ◽

pp. e11-e17 ◽

Cited By ~ 4

Author(s):

Nicolás Macías ◽

José M. Sayagués ◽

Carmen Esteban ◽

Manuel Iglesias ◽

Luís M. González ◽

...

Keyword(s):

Prognostic Factors ◽

Pancreatic Ductal Adenocarcinoma ◽

Tumor Grade ◽

Ductal Adenocarcinoma

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

Disease Markers ◽

10.1155/2021/6682697 ◽

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.

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Equipping the American Joint Committee on Cancer Staging for Resectable Pancreatic Ductal Adenocarcinoma with Tumor Grade: A Novel Staging System

Journal of Oncology ◽

10.1155/2020/9093729 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Hu Ren ◽

Chao-Rui Wu ◽

Guo-Tong Qiu ◽

Li-Peng Zhang ◽

Saderbieke Aimaiti ◽

...

Keyword(s):

Prognostic Factor ◽

Pancreatic Ductal Adenocarcinoma ◽

External Validation ◽

Staging System ◽

Tumor Grade ◽

Ductal Adenocarcinoma ◽

The Novel ◽

Operating Characteristics ◽

Discriminatory Ability ◽

American Joint Committee

Background. The 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) outperforms its previous version in reproducibility but not in survival discrimination. Tumor grade, an indicator of the aggressive biology of PDAC, has been suggested as a reliable prognostic factor. This study aimed to construct a novel staging system with greater prognostication for resectable PDAC by incorporating tumor grade into the 8th AJCC system. Methods. A total of 9966 patients with resectable PDAC from the Surveillance Epidemiology and End Results (SEER) database were randomly separated into training and interval validation sets. Another 324 patients from our center were included as an external validation set. We proposed a novel staging system by sorting the substages yielded by a combination of T, N, and tumor grade based on their overall survival (OS) and grouping them into several stages. Prognostic homogeneity and discrimination were determined using the likelihood ratio χ2 and the linear trend χ2 test, respectively. Prognostic accuracies were evaluated by the area under the receiver operating characteristics curve (AUC). Results. Using the 8th AJCC system, the prognosis of patients within the same stage was quite heterogeneous among different substages. The multivariate Cox model identified the tumor grade (hazard ratio 1.333, 95% confidence interval 1.250–1.423, p<0.001) was an independent prognostic factor of the OS. In the training set, the AUC, homogeneity, and discriminatory ability were superior for the novel staging system than for the 8th AJCC system (0.642 vs. 0.615, 403.4 vs. 248.6, and 335.1 vs. 218.0, respectively). Similar results were observed in the internal and external validation sets. Conclusions. The novel staging system incorporating tumor grade into the 8th AJCC system was associated with better prognostic accuracy, homogeneity, and discriminatory ability among resectable PDAC patients. Moreover, the novel staging system also allowed possibly adjuvant chemotherapy decisions.

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Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma

Cancers ◽

10.3390/cancers12010197 ◽

2020 ◽

Vol 12 (1) ◽

pp. 197 ◽

Cited By ~ 2

Author(s):

Moritz Reese ◽

Isabelle Flammang ◽

Zixuan Yang ◽

Sameer A. Dhayat

Keyword(s):

Survival Analysis ◽

Pancreatic Ductal Adenocarcinoma ◽

Liquid Biopsy ◽

Ductal Adenocarcinoma ◽

Total Serum ◽

Mesenchymal Transition ◽

Advanced Tumor ◽

Tumor Stages ◽

Positive Serum ◽

Serum Exosomes

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor entity, characterized by rapid disease progression, early metastatic dissemination, and late diagnosis at advanced tumor stages. Recently, we explored the clinical impact of several microRNAs (miR) associated with proliferation, epithelial-to-mesenchymal transition (EMT), and chemoresistance in tissue and blood serum specimens of PDAC patients. Here, we evaluated the potential of these miRs as diagnostic and prognostic biomarkers in PDAC in serum exosomes and their respective EpCAM-positive (epithelial cell adhesion molecule) subset. Expression analysis by RT-qRT-PCR (real-time quantitative reverse transcription polymerase chain reaction) revealed an overexpression of miR-200b and miR-200c in serum exosomes of PDAC patients as compared to healthy controls (p < 0.001; p = 0.024) and patients with chronic pancreatitis (p = 0.005; p = 0.19). Receiver operating characteristic (ROC) curve analysis showed that a biomarker panel consisting of miR-200b and miR-200c from total and EpCAM-positive serum exosomes enhanced the diagnostic accuracy of carbohydrate antigen 19-9 (CA.19-9) to 97% (p < 0.0001). Univariate survival analysis revealed a correlation between shorter overall survival (OS) and high expression of miR-200c in total serum exosomes (p = 0.038) and miR-200b in EpCAM-positive serum exosomes (p = 0.032), whereas EpCAM exosomal miR-200b was also indicative of shorter OS in the subgroup of patients treated with curative intent (p = 0.013). Multivariate survival analysis showed that miR-200b derived from EpCAM-positive serum exosomes might serve as an independent prognostic factor in PDAC (p = 0.044). Our findings indicate a potential role of exosomal miR-200 as diagnostic and prognostic liquid biopsy marker in PDAC and call for validation in a larger, multicenter setting.

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Comparison of 4- and 4 plus-courses S-1 administration as adjuvant chemotherapy for pancreatic ductal adenocarcinoma

BMC Cancer ◽

10.1186/s12885-021-08380-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Bo Li ◽

Shuo Shen ◽

Siting You ◽

Guoxiao Zhang ◽

Suizhi Gao ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Potential Benefit ◽

Primary Outcome ◽

Tumor Grade ◽

Ductal Adenocarcinoma ◽

Relapse Free Survival ◽

Free Survival ◽

Prolonged Duration ◽

Secondary Outcomes

Abstract Purpose The study aimed to investigate the potential benefit of more than 4 courses of S1 adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery. Method Data were retrospectively collected from consecutive patients who underwent S-1 adjuvant chemotherapy following curative pancreatectomy between January 2016 and December 2018. Four-courses and > 4 courses cohorts were compared for overall survival (OS) as a primary outcome, and relapse-free survival (RFS) and adverse event incidence as secondary outcomes. Results Four-courses and > 4 courses cohorts comprised 99 patients and 64 ones, respectively. TNM stage (stage II vs. I: HR, 2.125; 95% CI, 1.164–4.213; P = 0.015), duration of S-1 administration (4 vs. > 4 courses: HR, 3.113; 95% CI, 1.531–6.327; P = 0.002) and tumor grade (G3 vs. G1/2: HR, 3.887; 95% CI, 1.922–7.861; P < 0.001) were independent prognostic factors. Under the condition of patients’ survival time beyond 8 months, the OS of patients in > 4 courses cohort was significantly prolonged compared with that of 4 courses cohort (4 vs. > 4 courses: HR, 2.284; 95% CI, 1.197–4.358; P = 0.012), especially for patients in TNM stageII (4 vs. > 4 courses: HR, 2.906; 95% CI, 1.275–6.623; P = 0.011).RFS and adverse events incidence did not signifcantly difer between both cohorts. Conclusion Prolonged duration of S-1 intake is beneficial to prognosis of patients with PDAC resection.

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Dysadherin Overexpression in Pancreatic Ductal Adenocarcinoma Reflects Tumor Aggressiveness: Relationship to E-Cadherin Expression

Journal of Clinical Oncology ◽

10.1200/jco.2003.06.179 ◽

2003 ◽

Vol 21 (4) ◽

pp. 659-667 ◽

Cited By ~ 61

Author(s):

Takeshi Shimamura ◽

Michiie Sakamoto ◽

Yoshinori Ino ◽

Yasuto Sato ◽

Kazuaki Shimada ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Tumor Grade ◽

World Health ◽

Ductal Adenocarcinoma ◽

Tumor Aggressiveness ◽

Tumor Margins ◽

Poorly Differentiated ◽

Well Differentiated ◽

Health Organization ◽

E Cadherin

Purpose: The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, we reported the cloning and characterization of dysadherin and showed that it downregulated E-cadherin and promoted metastasis. The aim of this study was to investigate the clinical significance of dysadherin expression and the relationship between dysadherin expression and E-cadherin expression in pancreatic ductal adenocarcinoma. Patients and Methods: We examined dysadherin and E-cadherin expression in 125 surgically resected pancreatic ductal adenocarcinoma patients using immunohistochemistry. Results: Dysadherin was expressed at the cell membrane of cancer cells, but not in nontumor duct and acinar cells. Its expression was stronger in infiltrative and poorly differentiated nests compared with well-differentiated nests. Although the correlation between the expression of dysadherin and E-cadherin was not significant, a group of patients showed reduced E-cadherin expression with dysadherin overexpression. Increased dysadherin expression was significantly correlated with distant metastasis (P = .047), high tumor grade (P = .006), positive tumor margins (P = .024), and infiltrative type of growth pattern (P = .014). A survival advantage was observed in patients with 0% to 20% dysadherin-positive cells compared with patients with 51% to 100% dysadherin-positive cells, independent of tumor-node-metastasis classification, and World Health Organization tumor grade (P = .019). A combination of increased dysadherin expression and reduced E-cadherin expression (< 90%) further worsened the prognosis. Conclusion: In pancreatic ductal adenocarcinoma, dysadherin expression seems to reflect tumor aggressiveness and to be a positive marker of poor prognosis when considered both alone and in combination with downregulation of E-cadherin.

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