Objective To investigate the inhibitory effects of RNA interference (RNAi) expression vector on the expression of survivin in pancreatic cancer cell PANC-1. Methods The protein and mRNA expressions of survivin were examined with immunofluorescence and RT-PCR. The survivin gene was cloned into the T-vector and sequenced. The RNAi expression vectors targeting survivin, named si-svv-1 and si-svv-2 respectively according to whether they harbored a mutation or no mutation, were constructed and transfected into PANC-1 cells with liposome. The expression of survivin mRNA was detected with RT-PCR. Apoptosis of PANC-1 cells was analyzed with DNA ladder and FACS. Results There was a high degree expression of survivin in PANC-1 cells. The expression of survivin was not inhibited by RNAi expression vectors si-svv-1, but inhibited about (72.43±8.04)% by si-svv-2 and the apoptosis rate of PANC-1 cells increased to （12.36±1.44）% after 72 h. Conclusion The RNAi expression vector can effectively inhibit the expression of survivin in pancreatic cancer cell PANC-1 cells and induce the apoptosis in PANC-1 cells.
To study the mechanism of p16,Cyclin D1 and CDK4 and their relationship with pancreatic carcinoma, their expressions were examined by immunchistochemistry methods. Results: overpression of Cyclin D1 and CDK4 was revealed in these samples and p16 was undertectable. There was a negitive correlation between p16 and Cyclin D1 (Ｐ＜0.05), and a positive relation between Cyclin D1 and CDK4 (Ｐ＜0.05). The results indicate that abnormality of p16, Cyclin D1 and CDK4 may be involved in the molecular mechanism of pancreatic carcinoma, p16 lower expression and Cyclin D1 over expression may coexit in the development of pancreatic carcinoma.
ObjectiveTo investigate the relationship between insulin-like growth factor binding protein (IGFBP) gene with pancreatic cancer.
MethodsThe relevant literatures at home and abroad in recent years were reviewed. From the pancreatic cancer related genes, IGFBP related tumors and the correlation between IGFBP and pancreatic cancer research and other aspects of the previous research results were summaried.
ResultsMost of the studies suggested that IGFBP could inhibit the function of tumor cells through the IGF dependent pathway, but the deletion or mutation of IGFBP gene and its regulation mechanism are still unclear.
ConclusionIGFBP is closely related to the tumor, but its specific effects and mechanism of pancreatic cancer has not been settled. In order to affect the degree of cell differentiation, regulation of tumor growth and metastasis probability through the change of endogenous IGFBP gene level, the further studie is needed.
ObjectiveTo investigate the relation between disulfidptosis-related genes (DRGs) and prognosis or immunotherapy response of patients with pancreatic cancer (PC). MethodsThe transcriptome data, somatic mutation data, and corresponding clinical information of the patients with PC in The Cancer Genome Atlas (TCGA) were downloaded. The DRGs mutated in the PC were screened out from the 15 known DRGs. The DRGs subtypes were identified by consensus clustering algorithm, and then the relation between the identified DRGs subtypes and the prognosis of patients with PC, immune cell infiltration or functional enrichment pathway was analyzed. Further, a risk score was calculated according to the DRGs gene expression level, and the patients were categorized into high-risk and low-risk groups based on the mean value of the risk score. The risk score and overall survival of the patients with high-risk and low-risk were compared. Finally, the relation between the risk score and (or) tumor mutation burden (TMB) and the prognosis of patients with PC was assessed. ResultsThe transcriptome data and corresponding clinical information of the 177 patients with PC were downloaded from TCGA, including 161 patients with somatic mutation data. A total of 10 mutated DRGs were screened out. Two DRGs subtypes were identified, namely subtype A and subtype B. The overall survival of PC patients with subtype A was better than that of patients with subtype B (χ2=8.316, P=0.003). The abundance of immune cell infiltration in the PC patients with subtype A was higher and mainly enriched in the metabolic and conduction related pathways as compaired with the patients with subtype B. The mean risk score of 177 patients with PC was 1.921, including 157 cases in the high-risk group and 20 cases in the low-risk group. The risk score of patients with subtype B was higher than that of patients with subtype A (t=14.031, P<0.001). The overall survival of the low-risk group was better than that of the high-risk group (χ2=17.058, P<0.001), and the TMB value of the PC patients with high-risk was higher than that of the PC patients with low-risk (t=5.642, P=0.014). The mean TMB of 161 patients with somatic mutation data was 2.767, including 128 cases in the high-TMB group and 33 cases in the low-TMB group. The overall survival of patients in the high-TMB group was worse than that of patients in the low-TMB group (χ2=7.425, P=0.006). ConclusionDRGs are closely related to the prognosis and immunotherapy response of patients with PC, and targeted treatment of DRGs might potentially provide a new idea for the diagnosis and treatment of PC.
Objective To investigate the effect of common iliac vein allograft replacing the portal vein-superior mesenteric vein transition area invaded by pancreatic cancer. Methods The clinical data of a patient with pancreatic cancer admitted to the Beijing Tsinghua Changgung Hospital in December 2021 who underwent pancreaticoduodenectomy combined with common iliac vein allograft replacing the junction of portal vein, superior mesenteric vein and splenic vein were analyzed retrospectively. The patient was a 77-year-old man who complained of “epigastric pain for 1 month and pancreatic mass was found for 1 week”. After admission, the patient was diagnosed with pancreatic cancer through inspection, and then the surgery was required. Preoperative examination and intraoperative exploration confirmed that the junction of portal vein, superior mesenteric vein, and spleen vein was invaded by tumor. In addition, the length of the invaded vessels measured by preoperative 3D reconstruction image was 5.5 cm, and the distance between the broken end of portal vein and the broken end of superior mesenteric vein measured was 4.5 cm during the operation. After tumor and vessels were resected, vascular anastomosis could not be performed directly. After accurate evaluation, pancreaticoduodenectomy combined with common iliac vein allograft replacing the junction of portal vein, superior mesenteric vein and splenic vein was performed. The operative time was 11 h, and the intraoperative blood loss was 400 mL. After the operation, the routine treatment was performed in ICU and was transferred to the general ward on the 7th day. Postoperative laboratory tests were performed to monitor liver function changes routinely, and imaging examination were was performed to monitor portal venous system blood flow. Results Postoperative complications such as biliary fistula, pancreatic fistula, hemorrhage, infection and thrombosis were not occurred. Postoperative pathological diagnosis: pancreatic ductal adenocarcinoma, medium-low differentiation. Enhanced CT reexamination on the 2nd and 13th day after the operation showed that the blood flow at the junction of portal vein, superior mesenteric vein and splenic vein of the common iliac vein allograft was unobstructed, and there was no stenosis or thrombosis at each anastomosis. Conclusions The application of common iliac vein allograft replacing the portal vein-superior mesenteric vein transition area invaded by pancreatic cancer is safe and feasible. The short-term efficacy is satisfactory, and long-term prognosis remains to be further observed.
ObjectiveTo investigate the expression of circular RNA mitochondrial fusin 2 (circ-MFN2) in pancreatic cancer and analyze its correlation with clinicopathological features and prognosis.MethodsThe expressions of circ-MFN2 miRNA in 55 cases of pancreatic cancer tissues and serum were detected by qRT-PCR, and analyzed the correlation between circ-MFN2 and clinicopathological factors of pancreatic cancer and prognosis. The sensitivity, specificity and accuracy of expression of circ-MFN2 miRNA in the diagnosis of pancreatic cancer were statistically analyzed. ROC curve was used to analyze its efficacy as a biomarker for early diagnosis of pancreatic cancer.ResultsCompared with paracancerous tissues of pancreatic cancer and serum of healthy control group, circ-MFN2 miRNA was highly expressed in pancreatic cancer tissues and serum, and the difference were all statistically significant (all P<0.05). Chi square test showed that the expression of circ-MFN2 miRNA in pancreatic cancer tissues was not related to age, gender, tumor size, pathological type, and tumor site (P>0.05), but was significantly related to CA19-9 level, TNM stage, tumor differentiation and lymph node metastasis (P<0.05). The sensitivity, specificity and accuracy of expression of circ-MFN2 miRNA for pancreatic cancer were 72.7%, 70.9% and 83.6% respectively, which were all higher than that of CA19-9 (54.5%, 50.9% and 52.7%, P<0.05). Kaplan-Meier analysis showed that the median survival time of pancreatic cancer patients with high expression of circ-MFN2 miRNA was significantly shorter than that of patients with low expression (9.1 months vs 22.3 months, P<0.05). The area under ROC curve of circ-MFN2 miRNA as a serum biomarker for the diagnosis of pancreatic cancer was 0.861 [95%CI (0.775, 1.157), P=0.000]. Cox multivariate analysis showed that the expression of cirC-MFN2 miRNA and lymph node metastasis were independent risk factors for the prognosis of pancreatic cancer patients.ConclusionsCirc-MFN2 miRNA is highly expressed in pancreatic cancer tissues, and it is related to the clinical characteristics and prognosis of patients. It is expected to be a new molecular marker to predict the prognosis of pancreatic cancer.
ObjectiveTo systematically review the expression of E-cadherin protein and the risk of pancreatic cancer. MethodsWe searched PubMed, EMbase, The Cochrane Library, CNKI, VIP, CBM and WanFang Data from inception to October 2016 to collect case-control studies about the correlation between E-cadherin protein expression and the risk of pancreatic cancer. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.2 software and Stata 12.0 software. ResultsSeventeen studies (986 cases in pancreatic cancer group and 433 cases in normal pancreatic tissue group) were finally included. The results of meta-analysis showed that: the expression of E-cadherin protein in the pancreatic cancer group was lower than normal tissue group (OR=0.04, 95%CI 0.01 to 0.23, P=0.000 2), poor differentiation group was lower than high or middle differentiation group (OR=0.44, 95%CI 0.26 to 0.76, P=0.003), lymph node metastasis group was lower than without lymph node metastasis group (OR=0.50, 95% CI 0.31 to 0.81, P=0.005), and the difference was statistically significant. However, there was no significant difference between the clinical stageⅠ-Ⅱ group and Ⅲ-Ⅳ group (OR=0.63, 95%CI 0.25 to 1.59, P=0.33), pancreatic head cancer group and pancreatic body and tail cancer group (OR=1.22, 95%CI 0.72 to 2.07, P=0.46), pancreatic cancer with nerve invasion group and without nerve invasion group (OR=1.45, 95%CI 0.81 to 2.62, P=0.21), pancreatic cancer with vascular invasion group and without vascular invasion group (OR=0.55, 95%CI 0.13 to 2.22, P=0.40). ConclusionLower expression of E-cadherin protein is significantly associated with the risk of pancreatic cancer. Due to the limited quality and quanity of includied studies, the above conclusion should be approved by more studies.
ObjectiveTo systematically evaluate the potential value of C-reactive protein to albumin ratio (CAR) as an indicator of prognosis and survival in patients with pancreatic cancer. MethodsThe literatures were searched comprehensively in the PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang, CNKI, and CQVIP databases from the establishment of the databases to May 20, 2021. The combined hazard ratio (HR) and 95% confidence interval (95%CI) were used to evaluate the correlation between the CAR and the overall survival (OS), progression-free survival (PFS), or disease-free survival (DFS) in the patients with pancreatic cancer. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of the non-randomized controlled studies, and the Stata SE 15.0 software was used for meta-analysis. ResultsA total of 2 985 patients with pancreatic cancer were included in this meta-analysis of 15 studies. The results of meta-analysis showed that the higher CAR value, the shorter OS [effect size (ES)=0.60, 95%CI (0.50, 0.69), Z=12.04, P<0.001], DFS [ES=0.63, 95%CI (0.47, 0.78), Z=3.61, P<0.001], and PFS [ES=0.41, 95%CI (0.19, 0.63), Z=7.91, P<0.001] in the patients with pancreatic cancer. The results of subgroup analysis of OS according to different countries, sample size, mean age, follow-up time, CAR cut-off value, and NOS score showed that the higher CAR value was related to the shorter OS (P<0.05). The result of linear regression analysis showed that there was no correlation between the CAR cut-off value and lnHR of OS (r2=0.947, P=0.455). Conclusion From results of this study, CAR is closely related to OS of patients, and it is expected to be used as a new reference index for monitoring and judging prognosis of patients with pancreatic cancer.
Objective To investigate the expressions of CXCR4 and β-catenin in pancreatic cancer, explore the relationship between them, and explore the possible biomarkers about invasion and metastasis of pancreatic cancer. Methods Forty-eight samples of pancreatic cancer and 20 samples of normal pancreas tissues were selected. The expressions of CXCR4 and β-catenin were examined by the immunohistological technique. Spearman, Chi-square， and rank test were used to analyze the relation between the protein expressions and clinical characteristics. Survival analysis was evaluated by Kaplan-Meier product limit method and Log-rank test. Variables were evaluated by Cox proportional hazards analysis. The size of test was 0.05. Results The positive expression rates of CXCR4 and β-catenin in pancreatic cancer tissues were 85.4% (41/48) and 75.0% (36/48), respectively. Co-expression rate of CXCR4 and β-catenin was 70.8% (34/48). There were significant differences between various CXCR4 staining and lymph node metastasis and TNM stage (P=0.012, 0.005, respectively). β-catenin positive expression was associated with lymph node metastasis (P=0.047). However, abnormal β-catenin positive expression could not determine the clinical survival. Kaplan-Meier estimated curves suggested that clinical prognosis was poor for patients with CXCR4 expression. Multivariate analysis showed that CXCR4, late TNM stage, and lymph node metastasis were independent prognostic factors for pancreatic cancer. Conclusions Both CXCR4 and β-catenin abnormally express in pancreatic cancer. CXCR4 may be an important marker for pancreatic cancer progression.
ObjectiveTo summarize the latest research of long non-coding RNA (lncRNA) as competitive endogenous RNA (ceRNA) and its targeting technology in pancreatic cancer, so as to provide new ideas for lncRNA targeted intervention or as an early diagnostic marker of pancreatic cancer. MethodThe domestic and foreign literature on researches of lncRNA as ceRNA and its targeting technology in the pancreatic cancer was searched and reviewed. ResultsAt present, the growing number of evidences showed that in pathological states such as tumors, the abundance of intracellular lncRNAs was sufficient to trigger ceRNA crosstalk. The lncRNA played a role like “sponge” through the complementary binding of incomplete base of miRNA with miRNA response elements, then adsorbed miRNA, and thus changed the activity and effectiveness of miRNA. It also regulated the expression of downstream target genes. Moreover, a large number of studies had identified that the lncRNA-mediated ceRNA regulatory network, namely lncRNA/miRNA/mRNA axis, played a role in promoting or inhibiting the occurrence and progression of pancreatic cancer through a variety of cellular functions. In addition, many technologies targeting lncRNA, such as small interfering RNA, antisense oligonucleotides, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, and small molecule inhibitors, etc. had been widely studied and acquired important results in preclinical research. ConclusionsThe ceRNA hypothesis is a functional complex composed by non-coding RNAs and mRNAs with non-coding properties, forming a ceRNA network of multi-level and cross-regulatory on the transcriptome. Epigenetic modification and key post-transcriptional regulation of lncRNA have been achieved through ceRNA network mechanism, which has become a successful paradigm for exploring the function of lncRNA. The tumor suppressive and promoting effects and mechanisms of many lncRNAs in the occurrence and development of pancreatic cancer are explored in many studies. Moreover, the continuous progress of targeted lncRNA technology provides conditions for study of lncRNA. LncRNA has a potential to be used as a biomarker for precancerous diagnosis and prognosis of pancreatic cancer.
