ObjectiveTo explore the values of CA19-9, CA242, CEA, and CA125 single or combined detection on clinical diagnosis and prognosis for patients with pancreatic cancer. MethodsSerum tumor markers CA199, CA242, CEA, and CA125 of 63 patients with pancreatic cancer, 33 patients with cancer of bile duct, and 27 patients with benign pancreatic disease were detected, and those patients were followed up after operation. ResultsThe levels of CA19-9, CA242, CEA, and CA125 in patients with pancreatic cancer were significantly higher than those in patients with benign pancreatic disease and cancer of bile duct (Plt;0.05). The sensitivity of CA19-9 alone was the highest in the four tumor markers for the patients with pancreatic cancer 〔79.4% (50/63)〕, but the specificity (61.9%) was lower than that of CA242 (83.3%) and CEA (80.0%). The specificity of combined detection of CA199+CA242+CEA was the highest 〔93.3% (56/60)〕. The level of CA19-9 in carcinoma of body/tail of pancreas was significantly higher than that of carcinoma of pancreas head or whole pancreas (Plt;0.05). The serum levels of CA19-9 and CA242 in patients with stage Ⅳ were significantly higher than those in stage Ⅰ or Ⅱ/Ⅲ (Plt;0.05). Fifteen patients were lost to follow up, 48 patients were followed up 2－12 months with an average 6 months. The levels of CA242 and CA199 in patients with pancreatic cancer on 0.5 month and 3 months after operation were lower than those before operation (Plt;0.05). ConclusionsSingle detection of CA19-9 can improve the diagnostic sensitivity, and combined detection of tumor markers CA199+CA242+CEA can improve the diagnostic specificity. CA19-9 or CA242 is a valuable marker for evaluating treatment effects and estimating prognosis.
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 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 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.
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.
Objective To observe the expression of Galectin-3 and Galectin-1 in pancreatic cancer and explore the relationship between the expression and pathological grading. Methods Forty specimens of pancreatic carcinoma tissue and thirty-one specimens of normal pancreas tissue were selected, which were confirmed by surgical resection and pathology from 2002 to 2009. The expression of Galectin-3 mRNA and Galectin-1 mRNA in pancreatic cancer cell lines SW1990, PANC-1 and ASPC -1 was detected by means of reverse transcriptase-polymerase chain reaction; the expression of Galectin-3 protein and Galectin-1 protein in SW1990, PANC-1 and ASPC-1 was detected by means of immunocytochemistry; the expression of Galectin-3 protein and Galectin-1 protein in pancreatic cancer and normal pancreatic tissue was detected by means of immunohistochemistry. Results In SW1990, PANC-1 and ASPC-1, Galectin-3 mRNA signal and protein were detected, but no Galectin-1 mRNA signal or protein was detected. There was no expression of Galectin-3 protein or Galectin-1 protein in the 31 specimens of normal pancrease tissue, while there were Galectin-3 protein and Galectin-1 protein expressed in the 40 specimens of pancreatic cancer tissue. In the 40 specimens of pancreatic cancer tissue, the expression of Galectin-3 protein was observed in pancreatic cancer cells, but not in fibroblasts or matrix cells around the cancer mass; while the expression of Galectin-1 protein was observed in fibroblasts and matrix cells around the cancer mass, but not observed in pancreatic cancer cells. There was no significant association between the expression of Galectin-3 protein in pancreatic cancer and pathological grading (P>0.05); while the expression of Galectin-1 protein in pancreatic cancer was related to the pathological grading, and the expression of Galectin-1 protein was significant higher in poorly differentiated tumors than that in well/moderately differentiated tumors (P<0.05). Conclusions Galectin-3 or Galectin-1 is not expressed in normal pancreases; Galectin-3 is expressed in pancreatic cancer cells; Galectin-1 is expressed in fibroblasts and matrix cells around the cancer mass. The expression of Galectin-1 is related with the differentiation of pancreatic cancer.
ObjectiveTo study the expression of lipid associated with neutrophil gelatinase associated lipocalin (NGAL) in nude mice orthotopic pancreatic cancer tissues and the relationship between the occurred and development of pancreatic cancer. MethodsThe expressions of NGAL mRNA and protein of pancreatic cancer tissues and their adjacent tissues, and normal pancreatic tissues in nude mice were detected by using RT-PCR and immunohistochemical methods. ResultsThe expressions of NGAL mRNA in pancreatic cancer tissues and adjacent tissues were significantly higher than that in normal pancreatic tissues (P < 0.05), and the expression of NGAL mRNA in pancreatic carcinoma tissues was significantly higher than that in para carcinoma tissues (P < 0.05). The strong positive expression rate of NGAL protein in pancreatic carcinoma tissues was significantly higher than thoes in para carcinoma tissues and normal pancreatic tissues (P < 0.05). ConclusionsNGAL is highly expressed in pancreatic cancer tissues, and NGAL may be an important regulatory factor in the development of pancreatic cancer.
ObjectiveTo summarize current patient-derived organoids as preclinical cancer models, and its potential clinical application prospects. MethodsCurrent patient-derived organoids as preclinical cancer models were reviewed according to the results searched from PubMed database. In addition, how cancer-derived human tumor organoids of pancreatic cancer could facilitate the precision cancer medicine were discussed. ResultsThe cancer-derived human tumor organoids show great promise as a tool for precision medicine of pancreatic cancer, with potential applications for oncogene modeling, gene discovery and chemosensitivity studies. ConclusionThe cancer-derived human tumor organoids can be used as a tool for precision medicine of pancreatic cancer.
【Abstract】 Objective To explore the features of Ki-ras mutations at codon 12 in Chinese patients of pancreatic cancer and to compare these features with those in Western countries. Methods Fifty-nine samples were collected during operations for pancreatic adenocarcinoma in our hospital from December 1989 to November 1997. The patients, age ranged from 30 to 73 years 〔(55.5±10.4) years〕,with 38 males and 21 female. TNM staging of the patients: stage Ⅰ(n=4); stage Ⅱ(n=8), stage Ⅲ(n=42),stage Ⅳ(n=5). PCR was used to amplify target gene and Dot blot hybridization for detecting Ki-ras mutations at codon 12 was performed in fifty-nine specimens of Chinese pancreatic cancer. The data of Ki-ras mutations at codon 12 from Western countries were gotten by Medline system. Results Ki-ras mutation at codon 12 was detected in 76.3% of the patients in this group. The frequency of double mutation of Ki-ras at codon 12 in this group (15.6%) was highest than that in western countries. Our results were compared with those reported in Western countries. The results suggested that there were the significant differences in the substitution of Ki-ras mutations at codon 12 and in the ratio of transition to transversion in pancreatic cancer among various countries. Conclusion Ki-ras mutations at codon 12 is frequent in Chinese pancreatic cancer, and a gene component to pancreatic cancer may be different among various countries. In addition, the effect of Ki-ras mutations at codon 12 on prognosis of patients with pancreatic cancer is different in various countries.
Objective To systematically review the diagnostic value of combined detection of K-ras gene mutation in peripheral blood and serum tumor markers for pancreatic cancer. Methods Databases including PubMed, The Cochrane Library (Issue 3, 2016), Elsevier, BMJ, CBM, CNKI and WanFang Data were searched from 2000 to March 2016 to collect diagnostic tests about the diagnostic value of combined detection of K-ras gene mutation in peripheral blood and serum tumor markers in pancreatic cancer. Two reviewers independently screened literature, extracted data and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results A total of 23 studies involving 2 071 patients were included. The results of meta-analysis showed that the sensitivity (SE) and specificity (SP) of K-ras gene mutation in peripheral blood were 65% and 92% respectively in the diagnosis for pancreatic cancer. The results of the detection of tumor marker CA19-9 were 78% and 81% respectively. The SE and SP indexes in the parallel and serial combinations of CA19-9 together with CA242 were 85%, 72%, 70% and 83% respectively. And the SE, SP indexes in the parallel and serial combinations of K-ras gene mutation combined detection with CA19-9 were 90%, 63%, 47% and 96%. The positive likelihood ratio of the parallel combination of K-ras gene mutation in peripheral blood and CA19-9 (+LR=10.89) was higher than the other three detection methods, while the negative likelihood ratio of the serial combination of K-ras gene mutation in peripheral blood and CA19-9 (-LR=0.15) was lower than the other three detection methods, which indicated that the combined detection of K-ras gene mutation in peripheral blood and and CA19-9 had a better diagnostic performance than the single dectection of K-ras gene mutation or CA19-9 or the combined detection of CA19-9 and CA242 respectively. Comparing the area under curve (AUC) of SROC curve of the two combined diagnoses, the results showed that the diagnostic value of the parallel combination of K-ras gene mutation in peripheral blood and CA19-9 (AUC=0.87) was higher than that of the parallel combination of serum tumor markers CA19-9 and CA242. Conclusion Current evidence indicates that the combined detection of K-ras gene mutation and and tumor marker CA19-9 levels in peripheral blood can improve the diagnostic accuracy for pancreatic cancer. Due to the limited quantity and quality of included studies, above conclusions need to be verified by conducting more high quality studies.