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Cancer Medicine Feb 2023Pancreatic carcinoma (PC) is a highly lethal cancer with an increasing mortality rate, its five-year survival rate is only approximately 4%. N6-methyladenosine (m6A)...
BACKGROUND
Pancreatic carcinoma (PC) is a highly lethal cancer with an increasing mortality rate, its five-year survival rate is only approximately 4%. N6-methyladenosine (m6A) modification is the most common posttranscriptional modification of RNA, it could affect tumor formation by regulating m6A modifications in the mRNA of key oncogenes or tumor suppressor genes. However, its role in PC remains unclear.
METHODS
We combined bioinformatic analysis with in vitro and in vivo experiments to investigate the expression profile of methylation modulators and identify key m6A regulators in the progression of PC. Further study focused on exploring the target genes binding to the regulators through RIP and immunofluorescence staining experiment.
RESULTS
TCGA and Gene Expression Omnibus (GEO) analyses revealed an overall increasing trend in the expression of m6A regulators in PC, and consensus clustering analysis of m6A modification showed that the expression of regulators was negatively correlated with the survival rate. LASSO-Cox regression analysis revealed that IGF2BP2, METTL3, ALKBH5 and KIAA1429 were associated with hazard ratios (HR), but only IGF2BP2 was sufficiently appropriate for the m6A survival prognosis model. The IHC and WB results verified high protein expression of IGF2BP2 in PC, and IGF2BP2 knockdown inhibited the proliferation and migration of PC cells. We predicted and verified B3GNT6 was observably regulated by IGF2BP2 via RIP assays. In addition, IF staining confirmed the co-expression of IGF2BP2 and B3GNT6. The tumor-promoting effect of IGF2BP2 and its co-expression with B3GNT6 were verified in an animal model.
CONCLUSIONS
Elevated m6A levels promote PC progression. IGF2BP2 is a credible marker and modulates B3GNT6 mRNA stability, indicating that IGF2BP2 is a potential prognostic marker and therapeutic target in PC progression.
Topics: Animals; Methylation; RNA, Messenger; Pancreatic Neoplasms; RNA
PubMed: 35908253
DOI: 10.1002/cam4.5096 -
Biomedical Papers of the Medical... Dec 2023The main objective of this study was to determine the sensitivity of abdominal ultrasonography (US) in patients with isoattenuating pancreatic carcinoma and to compare...
AIMS
The main objective of this study was to determine the sensitivity of abdominal ultrasonography (US) in patients with isoattenuating pancreatic carcinoma and to compare the frequency of secondary signs on abdominal US and endoscopic ultrasonography (EUS) in these tumours.
METHODS
Twenty-four patients with histologically or cytologically verified isoattenuating pancreatic carcinoma who underwent abdominal US, contrast-enhanced CT and EUS of the pancreas as part of the diagnostic workup were included in this retrospective study. The sensitivity of abdominal US in detecting the isoattenuating pancreatic carcinoma was investigated and the frequency of secondary signs of isoattenuating pancreatic carcinoma on abdominal US and EUS was compared.
RESULTS
In 5 of 24 patients (21%) with isoattenuating pancreatic carcinoma, a hypoechogenic pancreatic lesion was directly visualised on abdominal US. Secondary signs were present on US in 21 patients (88%). These included dilatation of the common bile duct and/or intrahepatic bile ducts in 19/24 (79%), dilatation of the pancreatic duct in 3/24 (13%), abnormal contour/inhomogeneity of the pancreas in 1/24 (4%), and atrophy of the distal parenchyma in 1/24 (4%). Pancreatic duct dilatation was observed more frequently on EUS than on abdominal US (P=0.002). For other secondary signs, there was no significant difference in their detection on abdominal US and EUS (P=0.61-1.00).
CONCLUSION
Abdominal US is capable of detecting secondary signs of isoattenuating pancreatic carcinoma with high sensitivity and has the potential to directly visualise these tumours.
Topics: Humans; Retrospective Studies; Tomography, X-Ray Computed; Pancreatic Neoplasms; Pancreatic Ducts; Ultrasonography
PubMed: 35837719
DOI: 10.5507/bp.2022.032 -
World Journal of Gastroenterology Mar 2015This review highlights the rationale for dissection of the 16a2 and 16b1 paraaortic area during pancreaticoduodenectomy (PD) for carcinoma of the head of the pancreas.... (Review)
Review
This review highlights the rationale for dissection of the 16a2 and 16b1 paraaortic area during pancreaticoduodenectomy (PD) for carcinoma of the head of the pancreas. Recent advances in surgical anatomy of the mesopancreas indicate that the retropancreatic area is not a single entity with well defined boundaries but an anatomical site of embryological fusion of peritoneal layers, and that continuity exists between the neuro lymphovascular adipose tissues of the retropancreatic and paraaortic areas. Recent advances in surgical pathology and oncology indicate that, in pancreatic head carcinoma, the mesopancreatic resection margin is the primary site for R1 resection, and that epithelial-mesenchymal transition-related processes involved in tumor progression may impact on the prevalence of R1 resection or local recurrence rates after R0 surgery. These concepts imply that mesopancreas resection during PD for pancreatic head carcinoma should be extended to the paraaortic area in order to maximize retropancreatic clearance and minimize the likelihood of an R1 resection or the persistence of residual tumor cells after R0 resection. In PD for pancreatic head carcinoma, the rationale for dissection of the paraaortic area is to control the spread of the tumor cells along the mesopancreatic resection margin, rather than to control or stage the nodal spread. Although mesopancreatic resection cannot be considered "complete" or "en bloc", it should be "extended as far as possible" or be "maximal", including dissection of 16a2 and 16b1 paraaortic areas.
Topics: Carcinoma; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasm, Residual; Pancreatic Neoplasms; Pancreaticoduodenectomy; Treatment Outcome
PubMed: 25780282
DOI: 10.3748/wjg.v21.i10.2865 -
World Journal of Gastroenterology Sep 2003To study the correlation between pancreatic phase CT enhancement, intratumor microvessel density (MVD) and pathologic grading of pancreatic carcinoma and to evaluate the...
AIM
To study the correlation between pancreatic phase CT enhancement, intratumor microvessel density (MVD) and pathologic grading of pancreatic carcinoma and to evaluate the relationship between the degrees of CT enhancement and malignancy of pancreatic carcinoma.
METHODS
Thirty four patients with pancreatic carcinoma underwent CT scanning before resection. The enhancement degrees and forms of tumor were observed in pancreatic phase. The operative sample was stained with HE and CD34 marked by immunohistochemistry. MVD and histopathological grades of pancreatic carcinoma were examined. CT enhancement of the tumor, MVD counting in hot spot areas of neoplastic parenchymal cells and pathological grades of pancreatic carcinoma were comparatively analyzed.
RESULTS
Highly differentiated pancreatic adenocarcinoma was identified in 16 patients, moderately-differentiated tumor in 7 and poorly-differentiated in 11. Isodensity CT enhancement was demonstrated in 13 cases, slightly low density enhancement in 9, slightly low density enhancement with small cystic lesions in 9 and slightly low density enhancement with large cystic lesions in 3. The counting of MVD with CD34 marked by immunohistochemistry in hot spot areas of neoplastic parenchyma cells was small in 10 cases, medium in 16 and large in 8. The pathological grades correlated well with CT enhancement of the tumor (r=0.7857, P<0.001) and with MVD counting of tumor (r=0.3613, P<0.05). The CT enhancement of tumor correlated with MVD(r=0.6768, P<0.001).
CONCLUSION
There is an obvious and significant correlation between CT enhancement, pathological grades and MVD number in the hot spot areas of tumor. The extent of CT enhancement is inversely proportional to the malignant degree of pancreatic carcinoma, and to the MVD number in the hot spot areas of neoplastic parenchyma. The MVD in the hot spot areas of neoplastic parenchyma cells can also reflect the prognosis of the patients, and is directly proportional to the malignant degree of pancreatic carcinoma.
Topics: Adult; Aged; Carcinoma; Female; Humans; Image Enhancement; Male; Middle Aged; Neovascularization, Pathologic; Pancreatic Neoplasms; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 12970915
DOI: 10.3748/wjg.v9.i9.2100 -
Journal of the National Medical... Jan 1982A case of recurrent pulmonary embolism from thrombophlebitis associated with pancreatic carcinoma is reported. There is an increased incidence of thrombophlebitis with...
A case of recurrent pulmonary embolism from thrombophlebitis associated with pancreatic carcinoma is reported. There is an increased incidence of thrombophlebitis with all tumors, but carcinoma of the pancreas is statistically more frequently responsible. The higher incidence of thrombophlebitis with tumors of the body and tail of the pancreas is probably due to the low trypsin levels associated with these tumors. Trypsin levels are directly related to plasma antithrombin levels and mucinous adenocarcinomas are more commonly associated with thrombus formation.
Topics: Adenocarcinoma; Aged; Humans; Male; Pancreatic Neoplasms; Thrombophlebitis
PubMed: 7120446
DOI: No ID Found -
World Journal of Gastroenterology Apr 2020The incidence and mortality rates of pancreatic carcinoma (PC) are rapidly increasing worldwide. Long noncoding RNAs (lncRNAs) play critical roles during PC initiation... (Observational Study)
Observational Study
BACKGROUND
The incidence and mortality rates of pancreatic carcinoma (PC) are rapidly increasing worldwide. Long noncoding RNAs (lncRNAs) play critical roles during PC initiation and progression. Since the lncRNA DNAH17-AS1 is highly expressed in PC, the regulation of DNAH17-AS1 in PC was investigated in this study.
AIM
To investigate the expression and molecular action of lncRNA DNAH17-AS1 in PC cells.
METHODS
The PC expression data for the lncRNA DNAH17-AS1 was downloaded from The Cancer Genome Atlas database and used to examine its profile. Western blot and reverse transcription-quantitative PCR were employed to assess protein and mRNA expression. A subcellular fractionation assay was used to determine the location of DNAH17-AS1 in cells. In addition, the regulatory effects of DNAH17-AS1 on miR-432-5p, PPME1, and tumor activity were investigated using luciferase reporter assay, MTT viability analysis, flow cytometry, and transwell migration analysis.
RESULTS
DNAH17-AS1 was upregulated in PC cells and was associated with aggressive tumor behavior and poor prognosis for patients. Silencing DNAH17-AS1 promoted the apoptosis and reduced the viability, invasion, and migration of PC cells. In addition, DNAH17-AS1 served as a PC oncogene by downregulating miR-432-5p which normally directly targeted PPME1 to downregulate its expression.
CONLUSION
DNAH17-AS1 functions in PC as a tumor promoter by regulating the miR-432-5p/PPME1 axis. This finding may provide new insights for PC prognosis and therapy.
Topics: Apoptosis; Carboxylic Ester Hydrolases; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Male; MicroRNAs; Middle Aged; Pancreas; Pancreatectomy; Pancreatic Neoplasms; RNA, Long Noncoding; RNA, Small Interfering; Up-Regulation
PubMed: 32351291
DOI: 10.3748/wjg.v26.i15.1745 -
Cell Death & Disease Oct 2017The FOXO signaling pathway has been reported to have an important role in human cancer. Expression of miR-629 was markedly upregulated in pancreatic cancer and...
The FOXO signaling pathway has been reported to have an important role in human cancer. Expression of miR-629 was markedly upregulated in pancreatic cancer and negatively correlated with FOXO3. Therefore, exploring the regulatory mechanism of miR-629 and FOXO3 signaling may provide valuable clinical targets for pancreatic cancer therapy. In the current study, we found that overexpressing and inhibiting miR-629, respectively, enhanced and reduced the cell proliferation and metastasis of pancreatic cancer cells in vitro and in vivo compared with parental cells or cells transfected with a control vector. Furthermore, we found that miR-629 negatively regulated FOXO3 protein expression and decreased the activity of a luciferase reporter construct containing the FOXO3 3'-untranslated region. These results show that miR-629 regulates FOXO3 at the posttranscriptional level, resulting in enhanced cell proliferation and invasion of pancreatic carcinoma. Furthermore, we found that overexpressing miR-629 enhanced, while inhibiting miR-629 reduced, the stem cell-like phenotype of pancreatic cancer cells in vitro. A functional polymorphism at miR-629-binding site in the 3'-UTR of FOXO3 gene confers a decreased risk of progression in pancreatic carcinoma. Furthermore, these findings suggest that miR-629 has a vital role in promoting the development of pancreatic cancer and may represent a novel prognostic biomarker and therapeutic target.
Topics: Cell Proliferation; Disease Progression; Forkhead Box Protein O3; Humans; MicroRNAs; Pancreatic Neoplasms
PubMed: 29072689
DOI: 10.1038/cddis.2017.525 -
International Journal of Clinical and... 2015CD44 is a potentially interesting prognostic marker and therapeutic target in pancreatic cancer. The expression of CD44 has been reported to correlate with poor...
BACKGROUND
CD44 is a potentially interesting prognostic marker and therapeutic target in pancreatic cancer. The expression of CD44 has been reported to correlate with poor prognosis of pancreatic cancer in most literatures. The purpose of this study is to investigate the roles of CD44 in pancreatic caner, and their correlation with the prognosis of pancreatic cancer patients.
METHODS
67 pancreatic cancer samples were collected in Xinhua hospital affiliated to Shanghai Jiaotong University dating from Jan 2010 to Dec 2012. Immunohistochemistry was applied to test the expression of CD44 in pancreatic cancer. The clinical data of the patients were collected including their gender, age, the histology and location, lymph node metastasis and so on. The correlation between the CD44 expression and the clinicopathological factors of patients with pancreatic cancer was analyzed by the software SPSS 13.0. We devise and synthesis of effectively interference of shRNA sequence of CD44, which was transefected to the pancreatic cancer cells PANC-1. Colony formation assay, cell migration assays and western blot were performed.
RESULTS
The positive rates of CD44 expression in pancreatic samples were 73.1% (49/67). Univariate analysis showed that there were a significant differences between the CD44 expression and the pancreatic cancer' T staging, TNM staging, lymph node metastasis, the differentiation degree, tumor location (P < 0.05). The Cox proportional hazards model showed that differentiation, CD44 expression and nerve invasion were independent prognostic factors. Knockdown of CD44 expression in pancreatic cancer cells led to decreased cellular proliferation and migration ability, accompanied by downregulation of p-ERK and p-AKT.
CONCLUSION
CD44 were related to the distant metastasis and aggressive malignant behaviors of pancreatic cancer. CD44 may regulate tumorigenesis and cancer metastasis partially via PI3K/AKT or MAPK/ERK regulatory pathway.
Topics: Biomarkers, Tumor; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Immunohistochemistry; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Phosphorylation; Proportional Hazards Models; Proto-Oncogene Proteins c-akt; RNA Interference; Signal Transduction; Transfection
PubMed: 26261555
DOI: No ID Found -
World Journal of Gastroenterology Dec 2003DPC4 is a tumor suppressor gene on chromosome 18q21.1 that has high mutant frequencies in pancreatic carcinogenesis. The purpose of this study was to investigate the... (Comparative Study)
Comparative Study
AIM
DPC4 is a tumor suppressor gene on chromosome 18q21.1 that has high mutant frequencies in pancreatic carcinogenesis. The purpose of this study was to investigate the role of DPC4 alterations in tumorigenesis and progression of pancreatic carcinomas.
METHODS
We studied the immunohistochemical markers of DPC4 in 34 adenocarcinomas and 16 nonmalignant specimens from the pancreas. The 16 nonmalignant specimens from the pancreas included 8 non-neoplastic cysts and 8 normal pancreatic tissues. The relationship between DPC4 alterations and various clinicopathological parameters was evaluated by chi-square test or Fisher's exact test. Survivals were calculated using Kaplan-Meier method (by a log-rank test).
RESULTS
All the 16 nonmalignant cases of the pancreas showed expression of DPC4 gene. Loss of DPC4 expression was seen in 8 of 34(23.5%) pancreatic adenocarcinomas. The frequency of loss of DPC4 expression was higher in poorly differentiated adenocarcinoma (G3) than in well and moderately differentiated adenocarcinoma (G1 and G2) histologically (P=0.037). Loss of DPC4 expression of the patients at TNM stage IV was also higher than that of the patients at TNM stages I, II and III (60.0% at stage IV, versus 14.3% at stage I, 18.2% at stage II, and 18.2% at stage III) (P=0.223). The mean and median survival in patients with DPC4 expression was longer than those in patients with loss of DPC4 expression. Kaplan-Meier survival analysis demonstrated patients with DPC4 expression had a higher survival rate than patients with loss of DPC4 expression, but the difference did not reach statistical significance (P=0.879).
CONCLUSION
This study suggests that DPC4 is involved in the development of pancreatic carcinoma and is a late event in pancreatic carcinogenesis, DPC4 expression may be a molecular prognostic marker for pancreatic carcinoma.
Topics: Adenocarcinoma; Chromosome Mapping; Chromosomes, Human, Pair 18; DNA-Binding Proteins; Disease Progression; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Loss of Heterozygosity; Mutation; Pancreatic Neoplasms; Reference Values; Smad4 Protein; Survival Analysis; Trans-Activators
PubMed: 14669329
DOI: 10.3748/wjg.v9.i12.2764 -
Bioengineered Dec 2021Increasingly attention is being given to immune molecules in pancreatic cancer. The purpose of this study was to understand the potential clinical application of...
Increasingly attention is being given to immune molecules in pancreatic cancer. The purpose of this study was to understand the potential clinical application of immune-regulated genes (IRGs) in the stratification of prognosis and to facilitate the development of personalized prognostic information for pancreatic cancer patients. We systematically used public data to comprehensively analyze immune-regulated gene pair (IRGP) expression profiles and clinical data. In our study, IRGP signature was identified to predict the overall survival (OS) of pancreatic cancer patients. We suggested that immune genes are enriched in different risk groups. In the high-risk group, M1 macrophages and resting NK cells were significantly enriched, while the percentages of naïve B cells, resting dendritic cells, CD8 T cells and regulatory T cells (Tregs) were significantly higher in the low-risk group, and we verified these results with immunohistochemical experiments. Gene ontology (GO) analysis confirmed that the IRGP index (IRGPI) signature genes in the cohort were mostly party to sensory perception of a chemical stimulus and the adaptive immune response. The identification of these pathways provides a basis for studying the molecular mechanisms of IRGPI signaling to predict the prognosis of pancreatic cancer. Our study effectively constructed a robust IRGP signature with prognostic value for pancreatic cancer, presenting a conceivable method for deciding on a preoperative treatment.
Topics: Computational Biology; Gene Expression Regulation, Neoplastic; Humans; Macrophages; Pancreatic Neoplasms; Prognosis
PubMed: 33393862
DOI: 10.1080/21655979.2020.1860493