***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The objective of this study was to define prognostic serum biomarkers that could serve as surrogate survival endpoints during second-line treatment for advanced pancreatic cancer . This retrospective single-center study included patients treated with second-line therapy for advanced exocrine pancreatic cancer . A pretreatment value and at least one serial measurement during the first two cycles of second-line chemotherapy for CA 19 - 9 , CEA , CRP , and LDH had to be available in order to evaluate the prognostic role of kinetics on overall survival . A cutoff of a > 20 % increase from baseline during treatment was defined in order to form groups with suspected different outcomes . The effect of serial biomarker changes on survival was modeled by Cox proportional hazards regression in univariate and multivariate analyses . Overall , 70 patients treated with second-line therapy for advanced disease were included ; 94 % had distant metastases at treatment initiation .  Median time to progression was 2.7 months and median survival 5.4 months . Univariate analysis found that an increase of > 20 % during treatment was significantly associated with a worse overall survival for CA 19 - 9 ( HR 2.00 , p = 0.018 ) , CEA ( HR 2.38 , p = 0.004 ) , and CRP ( HR 3.06 , p < 0.001 ) . These associations remained significant within multivariate analysis for CEA ( HR 2.86 , p = 0.001 ) and CRP ( HR 3.20 , p = 0.001 ) . Serum biomarker kinetics might serve as useful prognostic tools during second-line chemotherapy in advanced pancreatic cancer Purpose : MicroRNAs ( miRNA ) have potential as diagnostic and prognostic biomarkers and as therapeutic targets in cancer . We sought to establish the relationship between miRNA expression and clinicopathologic parameters , including prognosis , in pancreatic ductal adenocarcinoma ( PDAC ) . Experimental Design : Global miRNA microarray expression profiling of prospect ively collected fresh-frozen PDAC tissue was done on an initial test cohort of 48 patients , who had undergone pancreaticoduodenectomy between 2003 and 2008 at a single institution . We evaluated association with tumor stage , lymph node status , and site of recurrence , in addition to overall survival , using Cox regression multivariate analysis . Validation of selected potentially prognostic miRNAs was done in a separate cohort of 24 patients . Results : miRNA profiling identified expression signatures associated with PDAC , lymph node involvement , high tumor grade , and 20 miRNAs were associated with overall survival . In the initial cohort of 48 PDAC patients , high expression of miR-21 ( HR = 3.22 , 95 % CI : 1.21–8.58 ) and reduced expression of miR-34a ( HR = 0.15 , 95 % CI : 0.06–0.37 ) and miR-30d ( HR = 0.30 , 95 % CI : 0.12–0.79 ) were associated with poor overall survival following resection independent of clinical covariates . In a further validation set of 24 patients , miR-21 and miR-34a expression again significantly correlated with overall survival ( P = 0.031 and P = 0.001 ) . Conclusion : Expression patterns of miRNAs are significantly altered in PDAC . Aberrant expression of a number of miRNAs was independently associated with reduced survival , including overexpression of miR-21 and underexpression of miR-34a . Summary : miRNA expression profiles for resected PDAC were examined to identify potentially prognostic miRNAs . miRNA microarray analysis identified statistically unique profiles , which could discriminate PDAC from paired nonmalignant pancreatic tissues as well as molecular signatures that differ according to pathologic features . miRNA expression profiles correlated with overall survival of PDAC following resection , indicating that miRNAs provide prognostic utility . Clin Cancer Res ; 18(2 ) ; 534–45 . © 2011 AACR Background Pancreatic cancer is one of the most deadly cancers , and serum carbohydrate antigen 19 - 9 ( CA19 - 9 ) level has been reported to be a useful prognostic marker in pancreatic cancer . The purpose of this study was to determine which prognostic factor ( preoperative or postoperative serum CA19 - 9 level ) is more useful . Methods Pre- and postoperative serum CA19 - 9 levels were measured in 109 patients who underwent surgical resection for pancreatic cancer between 1998 and 2009 , and their relationships to clinicopathological factors and overall survival were analyzed with univariate and multivariate methods . Results In univariate analysis , tumor location ( P = 0.019 ) , postoperative adjuvant chemotherapy ( P < 0.001 ) , residual tumor factor status ( P < 0.001 ) , UICC pT stage ( P = 0.004 ) , lymph node metastasis ( P = 0.015 ) , and UICC final stage ( P = 0.015 ) were significantly associated with overall survival . Differences in overall survival were significant between groups divided on the basis of four postoperative CA19 - 9 cutoff values ( 37 , 100 , 200 , and 500 U/ml ) but not significant between groups divided on the basis of the same four preoperative CA19 - 9 cutoff values . Pre- to postoperative increase in CA19 - 9 level also was significantly associated with poor prognosis . In multivariate analysis , postoperative adjuvant chemotherapy ( hazard ratio , 1.59 ; P = 0.004 ) and postoperative CA19  - 9 cutoff value of 37 U/ml ( HR , 1.64 ; P = 0.004 ) remained independent predictors of prognosis . Conclusions Postoperative CA19 - 9 level is a better prognostic factor than preoperative CA19 - 9 level , and curative surgery for resectable pancreatic cancer should be tried regardless of the preoperative CA19 - 9 level Background : The aim of this study was to identify whether preoperative CA19 - 9 levels might represent an independent prognostic marker for overall survival in patients undergoing resection for pancreatic ductal adenocarcinoma , and to describe the relationship between CA19 - 9 and tumour histology . Methods : 109 patients who had a pancreatoduodenectomy for pancreatic ductal adenocarcinoma with recorded preoperative CA19 - 9 levels were identified from a prospect ively maintained data base ( 1997–2006 ) . Multivariate analysis was conducted using a Cox proportional hazards model with continuous covariates where possible . Results : The median survival of 64 patients with a preoperative CA19 - 9 level > 150 kU/l was 10.4 months while in 45 patients with a CA19 - 9 level ≤150 kU/l this was 22.1 months ( corrected p = 0.012 ) . Also significant on univariate analyses were overall lymph node status ( p = 0.011 ) , lymph node ratio ( p = 0.003 ) and tumour diameter ( p = 0.004 ) . Preoperative CA19 - 9 levels > 150 kU/l were associated with a larger , more poorly differentiated tumour along with an increased likelihood of a positive resection margin status ( all p < 0.05 ) . Preoperative CA19 - 9 levels ( p = 0.030 ) and lymph node ratio ( p = 0.042 ) emerged as independent predictors of survival on multivariate analysis . Conclusions : Preoperative CA19 - 9 levels and lymph node ratio were significant predictors of survival in resected pancreatic ductal adenocarcinoma Introduction This study was undertaken to correlate serum CA 19 - 9 levels and CA 19 - 9 velocity with disease-free and overall survival  after pancreatectomy for adenocarcinoma . Methods From 1997 to 2002 , 96 patients underwent pancreatectomy without adjuvant chemotherapy as the control arm of a large r and omized prospect i ve adjuvant therapy trial . After resection , CA 19 - 9 levels were drawn at baseline , 4 weeks , and 12-week intervals thereafter . CA 19 - 9 velocity denotes rate of change in CA 19 - 9 levels over a 4-week period . Postoperative baseline CA 19 - 9 levels and CA 19 - 9 velocity were correlated with disease-free and overall survival . Data are presented as median ( mean ± SD ) . Results Disease-free survival was 7 months ( 14 ± 13.7 ) , and overall survival was 12 months ( 19 ± 14.3 ) with 24 ( 25 % ) patients alive at 41 months ( 39 ± 7.8 ) . Baseline CA 19 - 9 levels and CA 19 - 9 velocity predicted disease-free ( p < 0.01 ) and overall survival ( p < 0.01 ) . CA 19 - 9 velocity was a better predictor of overall survival than baseline CA 19 - 9 ( p < 0.001 ) . CA 19 - 9 velocity at disease progression was 131 U/ml/4-weeks ( 1,684 ± 4,474.8 ) vs. 1 U/ml/4-weeks ( 1 ± 3.8 ) at 22 months for patients without disease progression ( p < 0.001 ) . Conclusions CA 19 - 9 velocity predicts imminent disease progression after resection of pancreatic adenocarcinoma and is a better predictor of overall survival than baseline CA 19 - 9 levels . CA 19 - 9 velocity is a reliable and relatively inexpensive means of monitoring patients after resection of pancreatic cancer and should be considered in all patients enrolled in clinical trials as well as patients receiving adjuvant therapy Background : COX-2 is over-expressed in many cancers and precursor neoplasms including pancreatic cancer and in experimental setting s its overexpression has multiple tumorigenic effects including increasing proliferation and angiogenesis , and inhibition of apoptotic and immunologic responses . We evaluated the prognostic significance of COX-2 expression in pancreatic adenocarcinomas . Patients and Methods : We analyzed COX-2 expression by immunohistochemistry in a prospect i ve cohort of 299 patients with resectable infiltrating adenocarcinoma of the pancreas that had undergone a pancreaticoduodenectomy at Johns Hopkins Hospital between January of 1998 and July of 2003 . The survival associated with COX-2 expression was assessed by Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models that controlled for other known prognostic factors associated with pancreas cancer mortality . Results : By Kaplan-Meier analysis , patients whose pancreatic cancer cells expressed COX-2 ( median survival , 15 months ) had a significantly worse prognosis than patients whose tumor cells did not express COX-2 ( median survival , 20 months ; log rank , P=0.002 ) . In the multivariate Cox regression model ( which included tumor size , node status , margin status , histologic grade , and age ) , COX-2 expression remained independently prognostic of a worse survival with a hazard ratio ( HR ) of 1.41 ( 95 % CI 1.08 - 1.84 , P=0.01 ) . However , the adverse prognosis associated with COX-2 expression appeared greater in larger tumors : For tumors ≥ 3 cm in diameter , the HR was HR of 1.52 ( 95 % CI 1.04 - 2.22 ) versus 1.11 ( 95 % CI 0.75 - 1.67 ) in cancers < 3 cm . Conclusions : Tumor COX-2 expression portends a poor prognosis for patients with resected adenocarcinoma of the pancreas , particularly in tumors ≥ 3 cm PURPOSE CA 19 - 9 is an important tumor marker in patients with pancreatic adenocarcinoma . A secondary end point of Radiation Therapy Oncology Group trial 9704 was prospect i ve evaluation of the ability of postresectional CA 19 - 9 to predict survival . METHODS CA 19 - 9 expression was analyzed as a dichotomized variable ( < 180 v > or = 180 ) or ( < or = 90 v > 90 ) . Cox proportional hazards models were utilized to identify the impact of CA 19 - 9 expression on overall survival ( OS ) . Actuarial estimates for OS were calculated using Kaplan-Meier methods . RESULTS Three hundred eighty-five patients patients had assessable CA 19 - 9 levels . The majority had a CA 19 - 9 level lower than 180 or < or = 90 ( n = 220 and 200 , respectively ) , while 34 % were Lewis Antigen negative and 33 ( 9 % ) and 53 ( 14 % ) patients had levels higher than 180 and higher than 90 . When CA 19 - 9 was analyzed as a dichotomized variable , there was a significant survival difference favoring patients with CA 19 - 9 lower than 18 
    Output:
    
This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC