Top PDF Original Article Serum p53 antibodies as a prognostic marker in patients with pancreatic ductal adenocarcinoma (PDAC)

Original Article Serum p53 antibodies as a prognostic marker in patients with pancreatic ductal adenocarcinoma (PDAC)

Original Article Serum p53 antibodies as a prognostic marker in patients with pancreatic ductal adenocarcinoma (PDAC)

Changes in tumor antigens can lead to the development of autoantibodies, which result from over-expression, mutation, or altered deg- radation [1]. Tumor antigen-specific autoanti- bodies have been identified in the sera of patients with various types of solid tumors [2-5]. The long half-life and in vitro stability of these antibodies make them potential biomark- ers for detection and/or prognosis of cancer. p53, a well-established tumor suppressor pro- tein, plays a key role in the regulation of genes involved in cell cycle, DNA repair or apoptosis, thereby acting as a “gatekeeper” to maintain genomic stability [6]. In response to cellular or genotoxic stress, p53 can induce several res- ponses, including cell cycle arrest, senescence, differentiation, DNA repair and apoptosis [6, 7]. These functions are carried out, in part, by transactivating a series of genes involved in cell cycle control. Mutations in the p53 gene represent the most common genetic altera- tions in human cancers [8]. Most known p53 alterations are missense mutations occurring in the evolutionarily conserved exons 4-8.
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SPARC Expression as a Prognostic Marker in Pancreatic Ductal Adenocarcinoma

SPARC Expression as a Prognostic Marker in Pancreatic Ductal Adenocarcinoma

Background: The aim is to investigate whether secreted protein acidic and rich in cysteine (SPARC) expression could be considered as an independent prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Methods: The expression of SPARC in the tumor species was detected by immunoche- mistry and the effect of SPARC on the prognosis was analyzed by Kap- lan-Meier and Cox proportional hazard models. Results: Positive SPARC ex- pressions recognized in tumor and stroma were 31.33% and 64.66% respec- tively. The expression of SPARC in stroma was closely correlated with diffe- rentiation, vascular invasion and was an indicator for predicting poor out- come after surgery in Kaplan-Meier analysis. Univariate analysis and multiva- riate analysis showed the following factors to be significant: perineural inva- sion (HR = 2.098, 95% CI: 1.144 - 3.847) and stroma positive expression of SPARC (HR = 2.120, 95% CI: 1.307 - 3.440). Conclusions: High expression of SPARC in stroma was a promising pathological marker to predict the poor outcome in patients with pancreatic ductal adenocarcinoma.
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Original Article Expression of microRNA-200c in human pancreatic ductal adenocarcinoma and its prognostic significance

Original Article Expression of microRNA-200c in human pancreatic ductal adenocarcinoma and its prognostic significance

Abstract: Introduction: MicroRNAs (miRNAs) have emerged as potential therapeutic candidates due to their ability to regulate multiple targets involved in tumor progression. MiRNA-200c (miR-200c) was previously shown to be cor- related with aggressive clinicopathological features and poor prognosis in several cancers. The aim of this study was to analyze miR-200c expression in pancreatic ductal adenocarcinoma (PDAC) and to determine whether miR-200c has an independent prognostic value in PDAC. Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of miR-200c in human PDAC cells and tissue samples. The association of miR-200c expres- sion with clinicopathologic features was analyzed. Kaplan-Meier analyses were used to assess survival of patients. Univariate and multivariate analyses were performed using the Cox proportional hazards model to analyze the prognostic significance of miR-200c expression. Results: Our data showed that the relative level of miR-200c in PDAC cells was significantly lower than that in normal human pancreatic duct epithelial cell line. The expression of miR-200c in PDAC tissues was significantly lower than that in adjacent non-tumor tissues. By statistical analyses, low miR-200c expression was observed to be closely correlated with clinical stage, liver metastasis and lymphnode metastasis. Kaplan-Meier survival analysis revealed that patients with low miR-200c expression had a poor overall survival compared with the high miR-200c group (P < 0.05). Univariate and multivariate analyses showed that low miR-200c expression was an independent poor prognostic factor for PDAC patients. Conclusion: Our data demon- strated that reduced miR-200c in PDAC tissues was correlated with tumor progression, and miR-200c might be a potential molecular biomarker for predicting the prognosis of patients.
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Original Article Clinical impact and prognostic value of CD147 and MMP-7 expression in patients with pancreatic ductal adenocarcinoma

Original Article Clinical impact and prognostic value of CD147 and MMP-7 expression in patients with pancreatic ductal adenocarcinoma

and clinicopathological features. Prognostic analysis was carried out by using multivariate Cox regression mod- els. Results: Our results showed that expression of both CD147 and MMP-7 were increased in neoplastic tissue (P<0.001). MMP-7 expression in neoplastic tissue positively correlated with lymph node metastasis (P<0.05). Both CD147 and MMP-7 expression in neoplastic tissue had significantly impact on overall survival in patients with PDAC (P<0.05). More importantly, MMP-7 expression was correlated with the expression of CD147 in PDAC patients. Of 81 analyzed specimen, concurrent expression of CD147 and MMP-7 was found in 29 patients and had significantly negative impact on overall survival. Multivariate analysis determined that co-expression of CD147 and MMP-7 was an independent factor for prognosis. Conclusion: Our results indicate that CD147 and MMP-7 expression is associ- ated with overall survival in PDAC patients and concurrent expression of CD147 and MMP-7 could better predict the prognosis after surgery. The conclusion of this study can help physicians to make better follow-up decision to monitor the disease progression in PDAC patents.
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Original Article Expression of LRP16 in pancreatic ductal adenocarcinoma and its clinicopathological significance and prognostic value

Original Article Expression of LRP16 in pancreatic ductal adenocarcinoma and its clinicopathological significance and prognostic value

ciated with decreased survival time of the patients in univariate and multivariate analy- ses. Thus, LRP16 protein may play an impor- tant role in the carcinogenesis, progress and prognosis of PDAC in Chinese patients, and LRP16 expression detected by immunohisto- chemistry may be a simple and useful molecu- lar marker to predict the prognosis in PDAC patients. We might suggest a hypothesis that LRP16 might regulate the tumorigenesis and progress as an ERα coactivator. This study rais- es the possibility that anti-estrogen therapy could be used in the patients with high LRP16 expression in PDAC. However, the association between LRP16 and ER in PDAC development needs to be further investigated, from which LRP16 targeting with anti-estrogen therapy may be applied in PDAC.
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Prognostic value of microRNA 21 in pancreatic ductal adenocarcinoma: a meta analysis

Prognostic value of microRNA 21 in pancreatic ductal adenocarcinoma: a meta analysis

Although miR-21 holds a great promise as a novel prog- nostic biomarker for PADC, several limitations need to be addressed in practical application. Firstly, statistical het- erogeneity among pooled studies, which may be derived from different ethnicities (Caucasian vs. Asian), sample types (tissue vs. serum), treatment (without chemotherapy vs. with gemcitabine or 5-fluorouracil), different detection methods (qRT-PCR vs. ISH), decreased the plausibility of the results. Secondly, only studies published in English were pooled in this meta-analysis which may omit some valuable articles on this issue. Thirdly, miR-21 as a novel prognostic marker of PDAC just looms in recent years, and still limited research work was done. So, the study size obtained in this meta-analysis was relatively small.
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Clinical significance of elevated serum soluble CD40 ligand levels as a diagnostic and prognostic tumor marker for pancreatic ductal adenocarcinoma

Clinical significance of elevated serum soluble CD40 ligand levels as a diagnostic and prognostic tumor marker for pancreatic ductal adenocarcinoma

CD40 ligand (CD40L) was initially identified as a T-cell receptor for ligation of the co-stimulatory molecule CD40, and CD40-CD40L interaction was considered as a key event for effective adaptive immune response [1,2]. Sub- sequently, CD40L was identified on the surface of non- immune cells including activated platelets, endothelial cells, and epithelial cells [3-5]. Activated T-lymphocytes and platelets can release soluble CD40L (sCD40L) into circulation [3], and both membrane-bound CD40L and sCD40L can interact with CD40 which is expressed on vascular cells and activated platelets, resulting in pro- moting inflammatory and prothrombotic responses [3-6]. Additional studies reported that CD40-CD40L interaction produces many angiogenesis-associated factors, such as vascular endothelial growth factor (VEGF) [7-9]. Like this, early studies mainly focused on the pathophysiological role of CD40L in cardiovascular and immuno-inflamma- tory diseases [9,10]. However, subsequent other studies found that CD40-CD40L interaction affected tumor cell migration, and then the role of soluble CD40L (sCD40L) has gained interest in cancer [11]. Generally, tumor pro- coagulant activities cause thrombin generation, which induces platelet activation [12,13] and resultant release of angiogenesis-associated cytokines [14]. In cancer patients, sCD40L is more likely derived from activated platelets than from T-cells [15]; therefore, sCD40L can affect can- cer development and progression by inducing thrombotic reactions and releasing angiogenesis-associated cytokines. This idea is supported by evidence that cancer patients, including those with pancreatic ductal adenocarcinoma (PDAC), have significant platelet activation [16-18]. Wide- spread expression of CD40 in human carcinomas also supports the role of this ligand in cancer pathogenesis [19]. Actually, several recent human studies have showed the elevation of serum sCD40L levels in patients with certain solid tumors and myeloproliferative neoplasms [6,20-22]. But its exact role remains elusive yet.
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Original Article Expression of CD44 and prostate stem cell antigen and their prognostic significance in human pancreatic ductal adenocarcinoma

Original Article Expression of CD44 and prostate stem cell antigen and their prognostic significance in human pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers. Global sta- tistical data in 2015 ranked PDAC as the four- th leading cause of cancer deaths. More than 90% of PDAC patients are diagnosed at an advanced stage, when it is too late to carry out surgery. The overall 5-year survival rate is less than 10% [1]. It is widely accepted that cancer stem cells (CSCs) are responsible for the poor prognosis of incurable solid tumors. CSCs are implicated in many biological processes in pan- creatic cancers, including proliferation, differ- entiation, migration, invasion and resistance to therapy. Numerous studies have focused on the identification of CSC biomarkers to eluci- date their significance for predicting patient outcomes [2-6]. CD44 is a putative CSC marker and involved in various biological processes, such as extracellular matrix binding, embryonic development, cell proliferation, survival, inva- sion, migration and the epithelial-mesenchymal transition [7-11]. CD44 expression is associat- ed with overall survival (OS), tumor recurrence,
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Original Article FOXO3a expression and its diagnostic value in pancreatic ductal adenocarcinoma

Original Article FOXO3a expression and its diagnostic value in pancreatic ductal adenocarcinoma

A total of 61 patients undergoing surgical treat- ment for pancreatic malignancies or undergo- ing postoperative pathology confirmed as PDAC between January 2013 and January 2016 in the Second Hospital of Tianjin Medical University were enrolled in this study. The patients’ clinical, pathological, epidemiological, and prognostic data were collected. Among them, the average age was 61.6 years (range 39 to 79 years), the average size of the tumor was 3.8 cm (range 1 to 11 cm) and the median survival time was 21.0 months (range 3 to 45 months). All surgeries were completed success- fully, and the average operation time and intra- operative blood loss were 308.9 minutes (range 90 to 600 minutes) and 352.5 ml (range 50 to 1500), respectively. 48 (78.7%) patients underwent pancreatoduodenectomy, and 13 (21.3%) patients received a partial resection. Only 1 (1.6%) patient received neoadjuvant chemotherapy (gemcitabine + gimeracil and oteracil potassium) and 38 (62.3%) patients received adjuvant chemotherapy or radiothera- py. Meanwhile, 13 samples of normal tissues were obtained from the Department of Pathology of the Second Hospital of Tianjin Medical University. All tissues were fixed in 13% buffered formalin and paraffin embedded for immunohistochemistry.
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Original Article Risk factors for early-onset pancreatic cancer patients, and survival analysis

Original Article Risk factors for early-onset pancreatic cancer patients, and survival analysis

Abstract: Background: The median age of patients with pancreatic ductal adenocarcinoma (PDAC) is approximately 70 years, and it rarely affects individuals younger than 45 years, when it is defined as early-onset pancreatic cancer (EOPC). Little is known about risk factors and outcomes for EOPC patients. Aim: To evaluate the clinico-pathological features, risk factors, and outcomes of EOPC. Methods: A retrospective analysis of pancreatic cancer patients diag- nosed between January 1999 and December 2014 was performed. Information about environmental risk factors, clinical characteristics, treatment, and survival was collected. The risk factors of EOPC patients were compared to normal-onset pancreatic cancer (NOPC) patients. Results: Of 1789 patients with pathologically proven PDAC, 156 (8.7%) had EOPC. There was no difference regarding alcohol use, BMI, weight loss, and tumor location between EOPC and older subjects. EOPC patients were more likely to be male (75 vs. 63.9%) and to have a history of tobacco use (34.6% vs. 25.9%), compared NOPC patients. Among the 156 EOPC patients, there were 117 (75%) males, and 39 (25%) females, from 17 to 45 years old. Fifty-four (34.6%) had a smoking history, 55 had used alcohol, and 27 (17.3%) had a family history of cancer. For treatment, 32 underwent surgery to attempt curative resection of localized disease and 74 had palliative surgery. The median overall survival for the 156 EOPC patients was 8±0.5 months, with 1.2 years survival rates of 25.4 and 8%, respectively. For EOPC patients, the median overall survival of the patients treated with radical resection, palliative surgery, and medical treatment was 19±2.5, 8±0.6 and 6±0.3 months, respectively. The 1-year survival rates were 77.5, 17.6 and 4%, respectively. Survival analysis showed that the tumor size, tumor location, differentiation, treatment procedure, TNM stage, and first symptoms were associated with the overall survival (P < 0.05). Cox regression revealed that the TNM stage (RR=3.427; 95% CI: 1.802-6.519) and tumor size (RR=1.911; 95% CI: 1.054-3.463) are independent prognostic factors for EOPC patients. Conclusion: EOPC was associated with male gender and smoking history. Although EOPC patients display aggressive disease and have a worse outcome, radical resection is the best treatment. The TNM stage and tumor size are independent prognostic factors.
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Original Article Prognostic value of cancer stem cell marker CD133 expression in pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis

Original Article Prognostic value of cancer stem cell marker CD133 expression in pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis

Abstract: CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. Although the expression of CD133 has been re- ported to correlate with poor prognosis of PDAC in most literatures, some controversies still exist. In this study, we aimed to investigate the correlation between CD133 expression and prognosis and clinicopathological features in PDAC. A search in the Medline, EMBASE and Chinese CNKI (China National Knowledge Infrastructure) database (up to 1 March 2015) was performed using the following keywords pancreatic cancer, CD133, AC133, prominin-1 etc. Data from eligible studies were extracted and included into meta-analysis using a random effects model. Outcomes included overall survival and various clinicopathological features. We performed a final analysis of 723 patients from 11 evaluable studies for prognostic value and 687 patients from 12 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD133 for overall survival in PDAC was 0.58 (95% confidence interval (CI): 0.49-0.67) by univariate analysis and 0.73 (95% CI: 0.52-1.03) by mul- tivariate analysis. With respect to clinicopathological features, CD133 overexpression by immunohistochemistry (IHC) method was closely correlated with clinical TNM stage (TNM stage III+IV, OR=0.32, 95% CI: 0.19-0.54), tumor differentiation (poor differentiation, OR=0.56, 95% CI: 0.37-0.83), and lymph node metastasis (N1, 3.15, 95% CI: 1.56-6.36) in patients with PDAC. Our meta-analysis results suggest that CD133 is an efficient prognostic factor in PDAC. Overexpression of CD133 was significantly associated with clinical TNM stage, tumor differentiation and lymph node metastasis.
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Original Article SFRP5 as a prognostic biomarker for patients with pancreatic ductal adenocarcinoma

Original Article SFRP5 as a prognostic biomarker for patients with pancreatic ductal adenocarcinoma

tric cancer [11], colorectal cancer [12] and breast cancer [13]. The SFRP5 function as tumor suppressor gene has an important impli- cation in carcinogenesis, where they are down- regulated in many tumors [14]. In 168 primary breast carcinomas, JurgenVeeck et al, found that down regulation of SFRP5 was associated with reduced overall survival (OS) (P=0.045) and was an independent risk factor affecting OS in a multivariate Cox proportional hazard model. They indicated that SFRP5 might be a novel biomarker potentially useful in clinical breast cancer treatment [15]. Her-Young Su [16] suggested that epigenetic silencing of SFRP5 leaded to oncogenic activation and con- tributed to ovarian cancer progression and che- from six pairs of PDAC tissues, and found that
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Original Article Abnormal expression of Nek2 in pancreatic ductal adenocarcinoma: a novel marker for prognosis

Original Article Abnormal expression of Nek2 in pancreatic ductal adenocarcinoma: a novel marker for prognosis

Abstract: Nek2 is a serine/threonine kinase that has a critical role in mitosis during the cell division process. Despite its importance in centrosome regulation and spindle formation, no direct binders are reported between human pancreatic cancer and Nek2 protein. Our aim in studying Nek2 expression and survival in PDA patients is to determine whether Nek2 is a valuable prognostic factor in PDA tumorigenesis. We found that Nek2 mRNA was el- evated in PDA tissues. A high level of expression of Nek2 was significantly correlated with histological differentiation (P=0.042), lymph node metastasis (P=0.003) and tumor stage (P=0.001). Patients with a high Nek2 expression had a significantly worse overall survival (OS) than those patients with low Nek2 expression (P=0.002). Univariate and multivariate analysis revealed that high expression of Nek2 could serve as an independent predictor of poor prognosis. These results indicate that Nek2 could be a promising prognostic molecular marker and an attractive therapeutic target for PDA.
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<p>Prognostic significance of EIF4G1 in patients with pancreatic ductal adenocarcinoma</p>

<p>Prognostic significance of EIF4G1 in patients with pancreatic ductal adenocarcinoma</p>

information were excluded. We identified the prognostic significances of mRNAs in 3 independent cohorts. We then performed paired t-test or unpaired (Wilcoxon rank sum test) test to determine whether the statistically significant genes in all cohorts were increased in cancer tissues compared with those in normal tissues using the TCGA or GSE28735 cohorts. The overall process is described in Figure 1. These processes were performed in R software version 3.5.0 (The R Foundation for Statistical Computing, 2018) using the “cgdsr”, “TCGAbiolinks”, and “GEOquery” R packages.
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A study of Smad4, Smad6 and Smad7 in Surgically Resected Samples of Pancreatic Ductal Adenocarcinoma and Their Correlation with Clinicopathological Parameters and Patient Survival

A study of Smad4, Smad6 and Smad7 in Surgically Resected Samples of Pancreatic Ductal Adenocarcinoma and Their Correlation with Clinicopathological Parameters and Patient Survival

Previous studies have shown Smad7 overexpression in pancreatic cancer cell lines [22-24]. Similar to our study, few other studies have shown a loss of Smad7 in patient samples [24,25]. This difference in expression in cell lines as compared to tissue samples might be because of a possible reversal of phenotype in artificial tissue cul- ture systems. In our study, loss of Smad7 expression surpassed that of Smad4 and was absent in 56% of tumor samples, which is quite close to what has been reported by Guo et al [24]. Amongst clinicopathological parameters, loss of Smad7 significantly correlated with both tumor size as well as margin status. On similar lines, Wang et al showed a significant correlation between the low Smad7 expression and lymph node metastasis [26]. These observations, put together, indi- cate a role for Smad7 in the aggressiveness of this dis- ease. In fact, different studies have isolated different molecules, like KLF11, retinoblastoma, thioredoxin, which are involved in Smad7 dependent aggressiveness of pancreatic cancer [23,27,28]. However, unlike Wang et al, we did not find a significant correlation between loss of Smad7 and patient survival.
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Original Article EGFR expression in pancreatic intraepithelial neoplasia and ductal adenocarcinoma

Original Article EGFR expression in pancreatic intraepithelial neoplasia and ductal adenocarcinoma

[6] Ueda S, Ogata S, Tsuda H, Kawarabayashi N, Kimura M, Sugiura Y, Tamai S, Matsubara O, Hatsuse K and Mochizuki H. The correlation between cytoplasmic overexpression of epider- mal growth factor receptor and tumor aggres- siveness: poor prognosis in patients with pan- creatic ductal adenocarcinoma. Pancreas 2004; 29: e1-8.

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Neutrophil-Derived Proteases in the Microenvironment of Pancreatic Cancer -Active Players in Tumor Progression

Neutrophil-Derived Proteases in the Microenvironment of Pancreatic Cancer -Active Players in Tumor Progression

A link from infiltrating immune cells, such as neutrophils, in the micromilieu is directly tied to the role of Ras oncogenes, which are crucial for the pro- motion of malignant cellular transformation. Spar- mann and Bar-Sagi demonstrated that the inflamma- tory chemokine CXCL-8 (synonym: interleukin-8 or IL-8) is a transcriptional target of Ras signaling. In a tumor xenograft model, they show that Ras-dependent CXCL-8 secretion is required for the initiation of tumor-associated inflammation and neo- vascularization and concluded that Ras oncogene can elicit a stromal response that fosters cancer progres- sion [27]. Tumor cells for example from bronchial carcinoma or PDAC are able to attract PMN via tumor secreted chemokines such as CXCL-8 [28] or CXCL-16 [29]. The systemic inflammatory response from pan- creatic cancer cells promotes the infiltration of neu- trophils, which provide a favorable tumor environ- ment for cancer progression, by the secretion inter- leukins IL-2, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) [30]. In human PDAC, PMN infiltrates can be observed in the vicinity of tumor cells or in the stro- ma, which correlate with undifferentiated tumor growth and poor prognosis [31, 32]. Similar findings have also been observed in animal breast cancer models [33], renal cancer [34], or lung cancer [35]. In addition increased peripheral blood neutrophils are described in cancer patients [25]. The correlation be- tween TAN and tumor progression is not yet under- stood at a mechanistic level [25]. Some studies indi- cate that PMN have the potential to kill tumor cells, either directly [36] or by antibody-dependent
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Prognostic role of HER2 amplification based on fluorescence in situ hybridization (FISH) in pancreatic ductal adenocarcinoma (PDAC): a meta analysis

Prognostic role of HER2 amplification based on fluorescence in situ hybridization (FISH) in pancreatic ductal adenocarcinoma (PDAC): a meta analysis

There are some limitations of this study that should be considered. Firstly, the studies data included in this meta-analysis were all retrospective and nonrandomized ones, so the results may be limited for they are not the highest quality of evidence. Secondly, we cannot rule out that publication bias or heterogeneity between studies may lead to an underestimate of the correlations. Thirdly, we could not get enough data for subgroup analysis such as tumor stage, age, and gender from most of the included studies. Therefore, the prognostic value of HER2 amplifi- cation is not clear in subtypes of pancreatic cancer. The software GetData Graph Digitizer was applied to digitize and extract the data from the Kaplan-Meier curve in some
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Comparison and validation of the value of preoperative inflammation marker-based prognostic scores in resectable pancreatic ductal adenocarcinoma

Comparison and validation of the value of preoperative inflammation marker-based prognostic scores in resectable pancreatic ductal adenocarcinoma

In the present study, we demonstrated that NLR > 2.13 and PLR > 140 can be reliable predictive markers for shorter DFS and OS in a large and homogenous population of patients with resectable PDAC. After adjustment for a wide range of potential confounding factors, NLR > 2.13 and PLR > 140 remained independent unfavorable prognostic factors with clinically relevant HR values; however, these associations were not consistent among the patient subgroup with stage III tumors. Additionally, we presented a nomogram includ- ing NLR and PLR that predicts the 1-year DFS with good discriminative performance. To the best of our knowledge, this is the first nomogram for patients with resected PDAC incorporating inflammation-based prognostic indices to effectively predict DFS.
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Original Article Expression and functional perspectives of miR-184 in pancreatic ductal adenocarcinoma

Original Article Expression and functional perspectives of miR-184 in pancreatic ductal adenocarcinoma

With the elevating life level and changing of diet structure, the incidence and mortality of pan- creatic carcinoma (PC) is increasing in recent years, making it the fourth leading malignant tumor worldwide [1]. Due to its insidious onset, PC is relatively difficult to obtain an early diag- nosis. Such high-rate of misdiagnosis plus its inherent rapid progression, high degree of malignancy and difficulty in treatment, cause the 5-year overall survival rate of PC to be less than 1%, making it one of tumors with most unfavorable prognosis [2, 3]. Pancreatic ductal adenocarcinoma (PDAC), which derives from epithelial cells of pancreatic duct, is the most common type of PC and occupies more than 90% of all pancreatic exocrine tumors [4, 5]. In clinical practice, most PDAC patients already have tumor metastasis or invasion, thus mak- ing surgical resection impossible. Meanwhile, the insensitivity of PDAC against chemo- or ra-
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