High infiltration of CD3 + and CD8 + T-Lymphocytes correlate with improved overall survival and disease free survival in Pancreatic Cancer

Abstract Purpose An increasing number of studies have reported a significant association between long non-coding RNAs (lncRNAs) dysregulation and pancreatic cancers. In the present study, we aimed to gather articles to evaluate the prognostic value of long non coding RNA in pancreatic cancer. Experimental design We systematically searched all eligible articles from databases of PubMed, Web of Science, and Scopus to meta-analysis of published articles and screen association of multiple lncRNAs expression with clinicopathology and/or survival of pancreatic cancer. The pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival, disease-free survival and progression-free survival were measured with a fixed or random effects model. Results A total of 39 articles were included in the present meta-analysis. Our results showed that dysregulation of lncRNAs were linked to overall survival (39 studies, 4736 patients HR = 0.41, 95% CI 0.25 ± 0.58, random-effects in pancreatic cancer. Moreover, altered lncRNAs were also contributed to progression-free survival (8 studies, 1180 patients HR: 1.88, 95% CI (1.35–2.62) and disease-free survival (2 studies, 285 patients, HR: 6.07, 95% CI 1.28–28.78). In addition, our findings revealed the association between dysregulated RNAs and clinicopathological features in this type of cancer. Conclusions In conclusion, dysregulated lncRNAs could be served as promising biomarkers for diagnosis and prognosis of pancreatic cancer.

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Low hENT1 expression indicates poor prognosis in gemcitabine-treated pancreatic cancer patients

10.21203/rs.3.rs-19930/v1 ◽

2020 ◽

Author(s):

Jianchun Xiao ◽

Fangyu Zhao ◽

WenHao LUO ◽

Gang Yang ◽

Yicheng Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Poor Prognosis ◽

Disease Free Survival ◽

Treated Group ◽

Expression Level ◽

Free Survival ◽

Tumor Tissues ◽

Disease Free ◽

Low Expression

Abstract Background Pancreatic cancer (PC) is still a lethal disease and has a poor prognosis, gemcitabine-based chemotherapy is now the standard regimen in the treatment of pancreatic cancer. Gemcitabine resistance is an important obstacle for effective treatment of patients and improvement in patients’ overall survival (OS) and disease free survival (DFS). Methods We collected the surgical pathological tissue of pancreatic cancer patients who received radical surgery in our hospital from September 2004 to December 2014 continuously. 375 pancreatic cancer tissues and paired adjacent non-tumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of 4 TMAs was reexamined by HE staining. We did immunohistochemistry analysis to test hENT1 expression. The hENT1 antibody was used to measure hENT1 expression in TMAs by IHC staining according to standard protocols. Statistical analyses were performed using SPSS 22.0. The clinical end points of patients were calculated using Kaplan-Meier analysis and differences compared by log-rank test. Cox regression (proportional hazards model) was applied to determine the prognostic values of multivariate factors on patients’ overall survival (OS) and disease free survival (DFS). Results The hENT1 protein expression in tumor tissues was much lower than in normal tissues (80.5±8.8 versus 89.5±8.9, p=0.005). A low hENT1 expression level indicated a significant poor outcome of PC patients, including shortened DFS(21.6±2.8 months versus 36.9±4.0 months, p<0.001) and OS(33.6±3.9 versus 39.6±3.9, p=0.004). A high hENT1 expression level was related to longer DFS (35.7±4.0 versus 20.6±2.7; p<0.0001). Similarly, patients with high hENT1 expression in gemcitabine-treated group showed longer overall survival OS compared with low expression group (39.4±4.0 versus 31.5±3.9, p=0.001). In contrast, no significant difference of DFS and OS was found in non-gemcitabine treated group between the expression level of hENT1 and the prognosis of patients (p=0.413 and p=0.152). A low hENT1 expression level in tumor tissues was an independent risk factor for PC recurrence or metastasis(HR 0.53; 95% CI: 0.39-0.72; p<0.001). In addition, a low expression level of hENT1 (HR 0.60; 95%CI: 0.43-0.82; p=0.001) was independent risk factors for overall survival of PC. Low hENT1 expression level predicted worse OS (HR 0.60; 95%CI: 0.43-0.82; p=0.002) and DFS (HR 0.56; 95%CI: 0.41-0.77; p<0.001) . Conclusion hENT1 was low expressed in tumor tissues and this decreased expression level indicated a worse outcome (including shortened OS and DFS) in patients who received gemcitabine treatment postoperatively.

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Fluorophore-conjugated antibodies improve surgical resection of pancreatic cancer leading to prolonged disease-free survival and overall survival in orthotopic mouse models

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2012.06.330 ◽

2012 ◽

Vol 215 (3) ◽

pp. S127-S128 ◽

Cited By ~ 1

Author(s):

Cristina Angela Metildi ◽

Sharmeela Kaushal ◽

Mark A. Talamini ◽

George A. Luiken ◽

Robert M. Hoffman ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Surgical Resection ◽

Mouse Models ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free

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Immunotyping in tubo‐ovarian high‐grade serous carcinoma by PD‐L1 and CD8+ T‐lymphocytes predicts disease‐free survival

Apmis ◽

10.1111/apm.13116 ◽

2021 ◽

Author(s):

Akriti Bansal ◽

Radhika Srinivasan ◽

Manish Rohilla ◽

Bhavana Rai ◽

Arvind Rajwanshi ◽

...

Keyword(s):

T Lymphocytes ◽

Disease Free Survival ◽

Serous Carcinoma ◽

High Grade ◽

Free Survival ◽

Cd8 T Lymphocytes ◽

Disease Free

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Hepatic Artery Lymph Node in Pancreatic Cancer: A Retrospective Analysis of Survival Outcomes

10.21203/rs.3.rs-865990/v1 ◽

2021 ◽

Author(s):

Danny Conde ◽

Carlos Rey ◽

Manuel Pardo ◽

Andrea Recaman ◽

Juan Carlos Sabogal Olarte

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Lymph Node ◽

Hepatic Artery ◽

Vascular Invasion ◽

Lymph Node Ratio ◽

Disease Free Survival ◽

Free Survival ◽

Node Ratio ◽

Disease Free

Abstract BackgroundAfter optimal management, 5 years survival of pancreatic cancer is 12 - 15%. Factors associated with poor prognosis are tumoral histology, harvested regional lymph nodes, and recently, hepatic artery lymph node HLA(8a) involvement. In fact, evidence has shown negative impact of node 8a involvement on overall survival and disease free-survival. Therefore, we aimed to describe the prognostic significance of the HLA(8a) lymph node metastasis in terms of disease-free survival (DFS) and overall survival (OS) on a specific cohort of patients.MethodsA retrospective study was conducted based on a prospective database from the HPB department of patients who underwent a pancreaticoduodenectomy (PD) due to pancreatic cancer during 2014 - 2021. Overall survival (OS) and disease-free survival (DFS) were estimated to be associated with positive HLA(8a) using Kaplan-Meier analysis. Log Rank test and Cox proportional hazards regression analysis were used. Results111 patients were included, 55,4% female. The most frequent pathology was ductal adenocarcinoma (60.3%). Positive rate of the HLA(8a) node was 21.62%. Median OS time was 25.5 months, and median DFS time was 13,8 months. Positive HLA(8a) node, the cutoff of lymph node ratio (LNR) resection, and vascular invasion showed a strong association with OS. (CoxRegression p = 0.03 HR 0.5, p 0.003 HR = 1.8, p = 0.02 HR 0.4 CI 95%). In terms of DFS, lymph node ratio cutoff, tumoral size, and vascular invasion showed a statistically significant association with the outcome (p = 0.008, HR = 1.5; p= 0.04 HR=2.1; p=0.02 HR=0.4 CI 95%).Conclusion In this series of pancreaticoduodenectomies, OS and DFS are significantly reduced in patients with HLA(8a) node compromise in patients with pancreatic cancer. In multivariate analysis, lymph node status remains an independent predictor of OS and DFS. Further studies are needed.

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Prognostic relevance of ribonucleotide reductase small subunit p53R2 in pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15655 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15655-e15655

Author(s):

V. M. Chung ◽

X. Liu ◽

P. Chu ◽

Y. Yen

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Ribonucleotide Reductase ◽

Protein Level ◽

Disease Free Survival ◽

Small Subunit ◽

Migration Ability ◽

Free Survival ◽

Prognostic Relevance ◽

Disease Free

e15655 Background: Pancreatic cancer has the worst survival of any solid tumor, with most patients presenting with metastatic disease. Even after surgical resection the median survival is only 20 months suggesting micrometastatic disease. Ribonucleotide reductase is a critical enzyme in DNA synthesis and repair. Previous studies have shown that ribonucleotide reductase M2 (RRM2) subunit is associated with invasion and metastasis. Even though p53R2 has 80% homology to RRM2, its role is quite different. Here we report on the prognostic relevance of p53R2 in pancreatic cancer. Methods: Archived pathology specimens were obtained from 30 patients and immunohistochemistry for p53R2 performed on an IRB approved protocol (#06253). Clinical data was obtained by chart review and log-rank and Cox hazard proportional models were used to analyze overall and disease-free survival. Cell culture analysis was performed to further evaluate the role of p53R2. Utilizing a Matrigel chamber, invasive MiaPaCa-2 cells were collected for comparison to parental cells. Results: The median overall survival (OS) was 13.2 months (p53R2+) vs 8.5 months (p53R2-) (p=0.01). Disease free survival (DFS) was 12.4 vs 8.5 months respectively (p<0.05). By Western analysis, invasive cells have a higher protein level of RRM2 compared to parental cells. Interestingly, the protein level of p53R2 was low in the invasive cells suggesting an opposing role. To confirm this we inhibited p53R2 using siRNA which enhanced the migration ability of Mia PaCa-2 cells. Conclusions: Patients with p53R2 expression have improved disease-free and overall survival suggesting this may be used as a prognostic marker in pancreatic cancer patients. No significant financial relationships to disclose.

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Effect of platelet inhibition with perioperative aspirin on survival in patients undergoing curative resection for pancreatic cancer: a propensity score matched analysis

BMC Surgery ◽

10.1186/s12893-021-01083-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

E. Pretzsch ◽

J. G. D’Haese ◽

B. Renz ◽

M. Ilmer ◽

T. Schiergens ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Propensity Score ◽

Disease Free Survival ◽

Hematogenous Metastasis ◽

Control Group ◽

Metastasis Formation ◽

Free Survival ◽

Positive Effects ◽

Disease Free

Abstract Background The importance of platelets in the pathogenesis of metastasis formation is increasingly recognized. Although evidence from epidemiologic studies suggests positive effects of aspirin on metastasis formation, there is little clinical data on the perioperative use of this drug in pancreatic cancer patients. Methods From all patients who received curative intent surgery for pancreatic cancer between 2014 and 2016 at our institution, we identified 18 patients that took aspirin at time of admission and continued to throughout the inpatient period. Using propensity score matching, we selected a control group of 64 patients without aspirin intake from our database and assessed the effect of aspirin medication on overall, disease-free, and hematogenous metastasis-free survival intervals as endpoints. Results Aspirin intake proved to be independently associated with improved mean overall survival (OS) (46.5 vs. 24.6 months, *p = 0.006), median disease-free survival (DFS) (26 vs. 10.5 months, *p = 0.001) and mean hematogenous metastasis-free survival (HMFS) (41.9 vs. 16.3 months, *p = 0.005). Three-year survival rates were 61.1% in patients with aspirin intake vs. 26.3% in patients without aspirin intake. Multivariate cox regression showed significant independent association of aspirin with all three survival endpoints with hazard ratios of 0.36 (95% CI 0.15–0.86) for OS (*p = 0.021), 0.32 (95% CI 0.16–0.63) for DFS (**p = 0.001), and 0.36 (95% CI 0.16–0.77) for HMFS (*p = 0.009). Conclusions Patients in our retrospective, propensity-score matched study showed significantly better overall survival when taking aspirin while undergoing curative surgery for pancreatic cancer. This was mainly due to a prolonged metastasis-free interval following surgery.

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