PAK1 Expression in Pancreatic Cancer: Clinicopathological Characteristics and Prognostic Significance

Background: Improvement of the management of pancreatic cancer requires a better understanding of the genetic and molecular changes responsible for the development of the disease. The family of p21-activated kinases (PAKs) and especially PAK1 appears to mediate many cellular processes that contribute to the development and progression of pancreatic cancer, but the clinical relevance of PAK1 expression with the disease still remains unclear. Aim of the study was to assess the clinical value and the potential prognostic significance of PAK1 in pancreatic adenocarcinoma. Methods: We investigated the relationship between the PAK1 expression and the clinical and histopathologic characteristics of pancreatic cancer patients and the potential significance of PAK1 on survival. We examined tissue samples from 51 patients operated for pancreatic cancer. PAK1 expression was investigated with immunohistochemistry and correlated to clinicopathological parameters. Results: PAK1 was detected in all tumor samples and high expression was found in most patients. High PAK1 expression was also associated with younger age and well-differentiated tumors, but no association was found between PAK1 expression and Tumor-Node-Metastasis stage as well as deceased or alive status on follow-up. Moderate to high PAK1 expression favored higher 6-month and 1-year survival and low PAK1 expression 2-year survival but without statistical significance. Conclusions Our results indicate that PAK1 could potentially be used as a prognostic marker in pancreatic cancer. Further studies could clarify whether utilization of PAK1 in therapeutic protocols for the treatment of pancreatic cancer will render them more effective.

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Membranous Levels of C-Erbb-2 Oncoprotein in Gastric Cancer: Their Relationship with Clinicopathological Parameters and Their Prognostic Significance

The International Journal of Biological Markers ◽

10.1177/172460080401900403 ◽

2004 ◽

Vol 19 (4) ◽

pp. 268-274 ◽

Cited By ~ 3

Author(s):

F.J. Vizoso ◽

M.D. Corte ◽

A. Alvarez ◽

I. García ◽

J.M. del Casar ◽

...

Keyword(s):

Gastric Cancer ◽

Statistical Significance ◽

Prognostic Significance ◽

Clinicopathological Parameters ◽

Clinical Value ◽

Free Survival ◽

Gastric Carcinomas ◽

Novel Drug ◽

Immunoenzymatic Assay

Background The protein encoded by the c-erbB-2 gene is a membrane receptor expressed in a variety of solid human cancers and directly related to poor prognosis. The objective of this work was to evaluate the clinical value of the quantification of membranous oncoprotein levels in gastric cancer. Materials and methods Membranous c-erbB-2 levels were examined by means of a sandwich immunoenzymatic assay in 82 patients with gastric cancer. The median follow-up period for these patients was 16 months. In addition, c-erbB-2 expression was analyzed by immunohistochemistry in 57 gastric carcinomas. Results Membranous c-erbB-2 levels ranged widely in the studied tumors (44–112,000 NHU/mg protein). Median c-erbB-2 content was significantly higher in intestinal-type tumors than in diffuse-type tumors (p=0.01). In addition, high levels of c-erbB-2 were significantly associated with shorter relapse-free survival and overall survival in patients with resectable gastric carcinomas (p=0.01 and p=0.04, respectively). However, the correlation between immunohistochemistry and ELISA determinations did not reach statistical significance. Conclusion Our results suggest a potential prognostic value of membranous c-erbB-2 quantification by immunoenzymatic assay in gastric cancer. However, its possible role in the selection of patients with a view to the possible introduction of Herceptin as a novel drug against gastric cancer is at present uncertain.

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Associations of Individual and Joint Expressions of ERCC6 and ERCC8 with Clinicopathological Parameters and Prognosis of Gastric Cancer

10.21203/rs.3.rs-117489/v2 ◽

2021 ◽

Author(s):

Jing Chen ◽

Liang Li ◽

Li-Ping Sun ◽

Yuan Yuan ◽

Jing-jing Jing

Keyword(s):

Gastric Cancer ◽

Interaction Analysis ◽

Excision Repair ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Clinicopathological Parameters ◽

Double Negative ◽

Clinical Value ◽

Double Positive ◽

Tissue Samples

Abstract BackgroundExcision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) have been implicated in ailments such as genetic disease and cancer. However, the relationship between individual and joint expressions of ERCC6/ERCC8 and clinicopathological parameters as well as prognosis of gastric cancer (GC) still remains unclear.MethodsIn this study, protein expressions of ERCC6, ERCC8 and ERCC6-ERCC8 were detected by immunohistochemistry (IHC) with 109 paired GC and para-cancerous normal tissue samples. IHC results and RNA-seq data extracted from The Cancer Genome Atlas (TCGA) were used to explore the clinical value of ERCC6 and ERCC8 expression in GC. We further conducted protein-protein interaction analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene-gene interaction analysis for the exploration of the function and regulation network of ERCC6 and ERCC8 in GC.ResultsIndividual and joint ERCC6/ERCC8 expression were significantly higher in adjacent normal mucosa compared with GC tissues. Protein expressed levels of ERCC6, ERCC8, double negative ERCC6-ERCC8 and double positive ERCC6-ERCC8 and overexpressed ERCC6 mRNA were related to better clinicopathologic parameters, while overexpressed ERCC8 mRNA suggested worse parameters. Univariate survival analysis indicated an increased OS with higher ERCC6 protein expression and ERCC8 mRNA expression, and a decreased OS with double negative ERCC6-ERCC8 expression. Bioinformatic analyses showed ERCC6 and ERCC8 were associated with nucleotide excision repair (NER) pathway, and six and ten gene sets were figured out to be related with ERCC6 and ERCC8, respectively. Direct physical interactions were found between ERCC6 and ERCC8.ConclusionsIndividual and joint expressions of ERCC6/ERCC8 were associated with clinical features of GC. Expressed levels of ERCC6 and double negative ERCC6-ERCC8 protein, and ERCC8 mRNA were related to prognosis of GC. ERCC6 and ERCC8 primarily function in the NER pathway, and could regulate GC progression through the regulation of PI3K/AKT/mTOR pathway.

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Presence of variant histology (VarHst) in transurethral resection of bladder tumor (TURBT) biopsies and its prognostic significance on pathologic complete response (pCR) rates to neoadjuvant chemotherapy (neo-CTx).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.295 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 295-295

Author(s):

Jose Alexandre Pedrosa ◽

Kevin Rice ◽

Derek E. Thomas ◽

Paul Johnston ◽

Marietta L. Moore ◽

...

Keyword(s):

Multinomial Logistic Regression ◽

Statistical Significance ◽

Clinical Stage ◽

Pathologic Complete Response ◽

Prognostic Significance ◽

Phase Iii ◽

Cancer Center ◽

Clinical Value ◽

Curative Intent ◽

Clinical Databases

295 Background: Randomized phase III clinical trial data (S8710) supports an overall survival (OS) advantage with neo-CTx for muscle-invasive urothelial carcinoma (miUC) patients (pts) prior to cystectomy. Recent S8710 subset analyses have demonstrated an OS for pts with both pure UC and VarHst. pCR to neo-CTx has been suggested as a surrogate endpoint for OS. The relationship between VarHist in TURBT specimens and pCR rates is uncertain. Methods: A retrospective review of the Indiana University Simon Cancer Center urology and medical oncology clinical databases was performed spanning the years 1991 – 2012. Subjects with miUC, pathology reports available for both TURBT and cystectomy procedures, and confirmed receipt of neo-CTx with regimen details were included in this analysis. Pts with clinically positive lymph nodes (LN+) were included provided they underwent cystectomy with curative intent and distant metastases were not present. Associations between pCR and pt baseline age, gender, race, clinical stage (T2N0 vs. T3/T4/N+), chemotherapy regimen received (cisplatin combination therapy (CisCTx) vs. non-cisplatin based), and presence of VarHst on TURBT sample were tested by multinomial logistic regression analysis with statistical significance set at p<0.05. Results: 72 miUC pts satisfying the inclusion criteria were identified. Cohort demographics included: age (median) – 59 yrs, 76% male, 93% Caucasian, 63% T2N0, 32% LN+, 81% CisCTx neo-CTx regimen, 42% VarHst on TURBT, pCR for entire cohort 18%. The presence of VarHst on TURBT sample was not associated with decreased rates of pCR (6/30 vs. 7/42) p=0.610. A trend toward significance with age over 59 was also observed. Conclusions: The presence of VarHst in TURBT specimen is not associated with decreased rates of pCR at cystectomy in miUC pts treated with neo-CTx. Further characterization of the amount of VarHst and reproducibility of its recognition in TURBT samples is warranted to determine its ultimate clinical value.

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Expression of Multidrug Resistance-Associated Protein 2 in Human Gallbladder Carcinoma

BioMed Research International ◽

10.1155/2013/527534 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Hyun-Soo Kim ◽

Nam Chul Kim ◽

Kyu Hee Chae ◽

Gun Kim ◽

Won Seo Park ◽

...

Keyword(s):

Multidrug Resistance ◽

Gallbladder Carcinoma ◽

Imaging Techniques ◽

Prognostic Significance ◽

Clinicopathological Characteristics ◽

Lymphatic Invasion ◽

Tissue Samples ◽

Human Gallbladder ◽

Associated Proteins ◽

Aggressive Tumor

Gallbladder carcinoma (GBCA) is one of the most aggressive malignancies. It is usually diagnosed at an advanced stage, and prognosis remains poor despite advances in imaging techniques and aggressive surgical treatment. Overexpression of multidrug resistance-associated proteins (MRPs) in tumor cells is a major cause of the intrinsic multidrug resistance phenotype. Despite the documented importance of MRP expression in many carcinomas, the prognostic significance of MRP2 expression in primary GBCA is not known. Immunostaining for MRP2 was performed on tissue samples obtained from 143 patients with GBCA. We examined the association between MRP expression and clinicopathological characteristics and outcome of patients with GBCA. GBCA demonstrated MRP2 immunoreactivity in the apicolateral membranes of epithelial cells. MRP2 expression was positive in 53.1% (76/143) of GBCA samples. Positive MRP2 expression was significantly associated with the presence of local recurrence (P=0.038), lymphatic invasion (P=0.038), vascular invasion (P=0.023), and perineural invasion (P=0.006). In addition, the median survival time of patients with MRP2-positive GBCA (15 months) was significantly shorter than that of patients with MRP2-negative GBCA (85 months,P=0.011). We found that the expression of MRP2 in GBCA contributed to aggressive tumor behavior and poor prognosis, suggesting that MRP2 expression can be used as a potential prognostic biomarker of GBCA.

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Νεοαγγείωση καρκίνου παχέος εντέρου

10.12681/eadd/20810 ◽

2002 ◽

Author(s):

Πέτρος Παυλόπουλος

Keyword(s):

Shape Factor ◽

Malignant Tumors ◽

Statistical Significance ◽

Prognostic Significance ◽

Morphometric Parameters ◽

Critical Event ◽

Prognostic Information ◽

Poorly Differentiated ◽

Well Differentiated ◽

Axis Length

Background: Neovascularization reportedly is correlated with metastasis, recurrence, and prognosis in many types of solid tumors. Microvessel quantification in so-called "hot spots" has been studied extensively as the only factor reflecting angiogenesis in various malignant tumors. The objective of this study was to evaluate multiple morphometric microvascular characteristics in addition to microvessel density (MVD) in colorectal carcinomas to provide a better approach to examining the relation between angiogenesis and clinicopathologic factors and prognosis. Methods: Histologic sections from 106 colorectal adenocarcinomas and 17 adenomas, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to the vessel size (area, major axis length, minor axis length, perimeter, Feret diameter), shape (compactness, shape factor) or immunostaining intensity (proportion of intensely stained areas in relation to the total immunostained surface). Of the 123 cases investigated, 103 finally were evaluable in the statistical analysis, responding to the criteria of a high quality image depiction. Results: Carcinomas presented higher counts of microvessels compared to adenomas. MVD appeared to decrease with increasing Dukes stage. Carcinomas of lower Dukes stages (A and B) had a higher mean MVD than those of advanced stages (C and D). Although the difference did not reach statistical significance, well-differentiated neoplasms had lower MVD values than poorly differentiated ones. MVD was significantly correlated with the shape factor and compactness. All the morphometric parameters related to the size of microvessels had lower values in the group of adenomas. These parameters where significantly increased with progressing Dukes stage. Carcinomas with a higher histological differentiation had a significantly reduced TVA as compared to tumors with moderate or poor differentiation. Well-differentiated tumors had significantly lower values of shape factor and higher values of compactness in relation to poorly differentiated neoplasms. The vascular branching counts were significantly higher in carcinomas than in adenomas, and remained unaffected through progressing Dukes stages. Adenomas presented a more intense immunoreaction to FVIII as compared to carcinomas. Branching counts and TVA were the only factors of prognostic significance. Conclusions: This study provides evidence that neovascularization is an early critical event in colorectal tumorigenesis, reaching a maximum level early in the malignant process. Its prognostic significance is better assessed by quantification of TVA and the branching pattern of microvessels, whereas MVD does not provide significant prognostic information for colorectal carcinoma patients.

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Combined Texture Analysis of MR images and Glypican-3 to Identify the Differentiated Degree of Hepatocellular Carcinoma: a retrospective study

10.21203/rs.3.rs-16860/v1 ◽

2020 ◽

Author(s):

Mengmeng Feng ◽

Mengchao Zhang ◽

Yuanqing Liu ◽

Nan Jiang ◽

Qian Meng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Retrospective Study ◽

Texture Analysis ◽

Statistical Significance ◽

Area Under The Curve ◽

Texture Features ◽

Mr Images ◽

Clinical Value ◽

Enhanced Mri ◽

Well Differentiated

Abstract BACKGROUND To explore the clinical value of texture analysis of MR images (multiphase Gd-EOB-DTPA-enhanced MRI and T2 weighted imaging (T2WI) and the glypican-3 (GPC-3) to identify the differentiated degree of hepatocellular carcinoma (HCC). METHOD In this retrospective study, 104 participants were enrolled (GPC-3 data obtained in 51 participants). Each participant performed preoperative Gd-EOB-DTPA-enhanced MR scanning. Texture analysis was calculated by MaZda and then using the B11 program for data analysis and classification. The performance of texture features and GPC-3 in identifying the differentiated degree of HCC was assessed by receiver operating characteristic (ROC) analysis. RESULTS There were no statistically significances for the expression of GPC-3 between poorly-, well- and moderately-differentiated HCC. The area under the curve (AUC) of the combined texture features between poorly- and well-differentiated HCC, poorly- and moderately-differentiated HCC, moderately- and well-differentiated HCC was 0.812, 0.879 and 0.808 respectively. With GPC-3 combined, the AUC was increased to 0.868, while accuracy was decreased, in poorly- verse well-differentiated HCC, and the AUC and accuracy were the same as those without GPC-3 combined in poorly- verse moderately-differentiated HCC. Although the AUC was increased to 0.818 with GPC-3 combined in moderately- verse well-differentiated HCC, there were no statistical significance for the value change (p>0.05). CONCLUSION S Texture analysis of Gd-EOB-DTPA-enhanced MRI and T2WI are valuable in identifying the differentiated degree of HCC. There is no significant effect of GPC-3 in identifying the differentiated degree of HCC, suggesting the promising value of texture analysis of MR images in the precise presurgical diagnosis of HCC.

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Expression of Genomic Instability-Related Molecules: Cyclin F, RRM2 and SPDL1 and Their Prognostic Significance in Pancreatic Adenocarcinoma

Cancers ◽

10.3390/cancers13040859 ◽

2021 ◽

Vol 13 (4) ◽

pp. 859

Author(s):

Anna Klimaszewska-Wiśniewska ◽

Karolina Buchholz ◽

Izabela Neska-Długosz ◽

Justyna Durślewicz ◽

Dariusz Grzanka ◽

...

Keyword(s):

Cancer Progression ◽

Statistical Significance ◽

Prognostic Significance ◽

Bioinformatic Analysis ◽

The Cancer Genome Atlas ◽

Ductal Adenocarcinoma ◽

Clinicopathological Parameters ◽

Mrna Levels ◽

Poor Overall Survival ◽

Cyclin F

In the present study, we aimed to assess the selected components of cell cycle machinery, checkpoint, DNA repair, and synthesis, namely RRM2, cyclin F, and SPDL1 in pancreatic adenocarcinomas (PAC) by in-house immunohistochemistry (IHC) and bioinformatic analysis of public datasets, in terms of expression, correlation with clinicopathological parameters, and patient survival. Sixty eight patients with pancreatic ductal adenocarcinoma (PDAC) were included in our cohort study, and IHC was performed on tissue macroarrays. RNA-Seq-based transcriptome data for 177 PACs were retrieved from the Cancer Genome Atlas (TCGA). We found cyclin F, RRM2, and SPDL1 to be overexpressed at both protein and mRNA levels in tumor tissues compared to respective controls. Based on TCGA dataset, we have demonstrated that CCNF, RRM2, and SPDL1 are potent independent prognostic markers for poor overall survival, both by themselves and even more in combination with each other. Furthermore, high CCNF mRNA expression was associated with features of cancer progression. By contrast, overexpression of cyclin F or SPDL1 proteins denoted a good prognosis in PDAC patients; however, in the case of the former protein, the results did not reach statistical significance. Specifically, high levels of SPDL1 protein emerged as the most powerful independent prognostic factor associated with a better outcome. If validated, the CCNF/RRM2/SPDL1 three-gene panel developed in this study, as well as SPDL1 protein, may provide significant clinical implications for the prognosis prediction of PAC patients.

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ROR1 and ROR2 expression in pancreatic cancer

BMC Cancer ◽

10.1186/s12885-021-08952-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dongli Liu ◽

George Sharbeen ◽

Phoebe Phillips ◽

Amber L. Johns ◽

Anthony J. Gill ◽

...

Keyword(s):

Pancreatic Cancer ◽

Protein Expression ◽

Mrna Expression ◽

Mrna Level ◽

Prognostic Significance ◽

Wnt Signalling ◽

Ductal Adenocarcinoma ◽

Clinicopathological Parameters ◽

Cytoplasmic Staining

Abstract Background The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unknown. Only one study has investigated the prognostic significance of the noncanonical Wnt signalling receptor, ROR2 in PDAC. No studies have investigated the prognostic role of ROR1 in PDAC. Methods Here, we performed analysis of ROR1 and ROR2 mRNA expression in three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD (n = 150) and CPTAC-PDAC (n = 137). ROR1 and ROR2 protein expression from the CPTAC-PDAC discovery cohort were also analysed. Immunohistochemistry (IHC) using the validated anti ROR1 monoclonal antibody (4A5) was performed on the Australian Pancreatic Cancer Genome Initiative (APGI) cohort of PDAC samples (n = 152). Association between ROR1 cytoplasmic staining intensity and clinicopathological parameters including stage, grade and overall survival (OS) was investigated. Results High ROR1 mRNA expression levels correlated with a favourable OS outcome in all of the ICGC-PACA-AU, TCGA-PAAD and CPTAC-PDAC cohorts. ROR1 protein expression was not associated with stage, grade or OS in the APGI cohort. Conclusion ROR1 and ROR2 have potential as prognostic markers when measured at the mRNA level in PDAC. Our IHC cohort did not support ROR1 protein expression in predicting OS, and highlighted the discrepancy of prognostic biomarkers when measured by MS, IHC and RNAseq.

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Associations of Individual and Joint Expressions of ERCC6 and ERCC8 with Clinicopathological Parameters and Prognosis of Gastric Cancer

10.21203/rs.3.rs-117489/v1 ◽

2020 ◽

Author(s):

Jing Chen ◽

Liang Li ◽

Li-Ping Sun ◽

Yuan Yuan ◽

Jing-jing Jing

Keyword(s):

Gastric Cancer ◽

Interaction Analysis ◽

Excision Repair ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Clinicopathological Parameters ◽

Double Negative ◽

Clinical Value ◽

Double Positive ◽

Tissue Samples

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Elevated Serum Interleukin-8 Level Correlates with Cancer-Related Cachexia and Sarcopenia: An Indicator for Pancreatic Cancer Outcomes

Journal of Clinical Medicine ◽

10.3390/jcm7120502 ◽

2018 ◽

Vol 7 (12) ◽

pp. 502 ◽

Cited By ~ 21

Author(s):

Ya-Chin Hou ◽

Chih-Jung Wang ◽

Ying-Jui Chao ◽

Hao-Yun Chen ◽

Hao-Chen Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Weight Loss ◽

Disease Progression ◽

Locally Advanced ◽

Prognostic Significance ◽

Elevated Serum ◽

Body Weight Loss ◽

Serum Levels ◽

Prognostic Indicator ◽

Tissue Samples

Cancer cachexia (CC), characterized by body weight loss and sarcopenia, contributes to over 20% of all cancer-related death. Approximately 80% of pancreatic cancer (PC) patients develop CC during disease progression. Pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, have been correlated with CC; however, its prognostic significance remains unclear. In this study, serum levels of the CC-related cytokines were determined in normal donors and PC patients. IL-8 expression was assessed in PC tissue microarrays. The correlation of levels of each cytokine with disease progression, weight loss, and sarcopenia was calculated. The relationships among the baseline variables, CC, and IL-8 expression with disease progression were examined using univariate and multivariate analyses. Of these mentioned cytokines, only serum IL-8 level was elevated in the locally advanced group (n = 55) compared with the normal (n = 17) and resected groups (n = 55). Serum IL-8 level was positively correlated with CC status, weight loss, sarcopenia, but was negatively correlated with total psoas area (TPA). IL-8 expression in tissue samples was also positively associated with weight loss. Furthermore, serum IL-8 level was an independent predictor of survival. In conclusion, elevated serum IL-8 level significantly correlates with CC and sarcopenia and can be used as a prognostic indicator in PC.

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