title: Low RASSF6 expression in pancreatic ductal adenocarcinoma is associated with poor survival.
abstract: OBJECTIVE
  To analyze RASSF6 expression in pancreatic ductal adenocarcinoma (PDAC) and to determine whether RASSF6 has an independent prognostic value in PDAC.
  
  
  METHODS
  We studied RASSF6 expression in 96 histologically confirmed PDAC samples and 20 chronic pancreatitis specimens using immunohistochemistry and real-time quantitative reverse transcription-PCR. PDAC issues were then classified as RASSF6 strongly positive, weakly positive or negative. RASSF6 mRNA and protein expression in PDAC samples with strong positive staining was further evaluated using real-time PCR and Western blot analysis. Lastly, correlations between RASSF6 staining and patients' clinicopathological variables and outcomes were assessed.
  
  
  RESULTS
  RASSF6 was negatively expressed in 51 (53.1%) PDAC samples, weakly positively expressed in 29 (30.2%) and strongly positively expressed in 16 (16.7%), while its expression was much higher in para-tumor tissues and chronic pancreatitis tissues. Positive relationships between RASSF6 expression and T-stage (P = 0.047) and perineural invasion (P = 0.026) were observed. The median survival time of strongly and weakly positive and negative RASSF6 staining groups was 33 mo, 15 mo and 11 mo, respectively. Cox multivariate analysis indicated that RASSF6 was an independent prognostic indicator of overall survival in patients with PDAC. A survival curve analysis revealed that increased RASSF6 expression was correlated with better overall survival (P = 0.009).
  
  
  CONCLUSIONS
  RASSF6 expression is an independent biomarker of an unfavorable prognosis in patients with PDAC.
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Ye
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Dou-Dou
authors.initials: DD
authors.lastname: Li
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Quan-Bo
authors.initials: QB
authors.lastname: Zhou
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Fu
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Gao
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Rui-Wan
authors.initials: RW
authors.lastname: Chen
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Ru-Fu
authors.initials: RF
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis* / Q000235:genetics; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C519911:RASSF6 protein, human; D012333:RNA, Messenger; D020559:Monomeric GTP-Binding Proteins
keywords: Immunohistochemistry; K-ras; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Prognostic marker; RASSF6; Survival analysis