A single-nucleotide polymorphism in tumor suppressor gene SEL1L as a predictive and prognostic marker for pancreatic ductal adenocarcinoma in caucasians

被引:14
|
作者
Liu, Qian
Chen, Jinyun
Mai, Billy [2 ]
Amos, Christopher
Killary, Ann M. [3 ]
Sen, Subrata [4 ]
Wei, Chongjuan
Frazier, Marsha L. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Unit 1365, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Sch Hlth Profess, Program Mol Genet Technol, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA
关键词
pancreatic cancer; SNP; biologic marker; cigarette smoking; treatment; ENDOPLASMIC-RETICULUM; NEGATIVE REGULATOR; IN-VITRO; CANCER; EXPRESSION; SMOKING; LIN-12; GLP-1; SEL-1; P16;
D O I
10.1002/mc.20808
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
SEL1L is a putative tumor suppressor gene that is frequently down-regulated in pancreatic ductal adenocarcinoma (PDA). A single-nucleotide polymorphism (SNP) rs12435998 in intron3 of SEL1L has previously been reported to be associated with susceptibility to Alzheimer's disease. We hypothesized that this SNP may influence clinical outcomes of patients with PDA. We analyzed DNA samples from 497 Caucasian patients with pathologically confirmed primary PDA. Of these, 98 had been enrolled in a clinical trial of neoadjuvant chemo-radiotherapy and 77 of the 98 had subsequently undergone pancreaticoduodenectomy (PD). We performed KaplanMeier analysis to evaluate the correlation between different SNP genotypes and age at diagnosis, survival time after diagnosis, and survival time after PD. In nonsmokers, we found a significant difference in median age at diagnosis between variant genotypes (AG/GG) carriers and wild-type genotype (AA) carriers (58 vs. 62 yr; log-rank test, P?=?0.017). Patients with variant genotypes also showed an increased hazard ratio (HR) of 1.45 [95% confidence interval (CI), 1.071.97] relative to wild-type genotype. Among the patients in the clinical trial, the variant genotypes carriers had a median post-PD survival time that was 34.7 months shorter than wild-type genotype carriers (log-rank test, P?=?0.019; HR, 1.91; 95% CI, 1.093.34). Our results suggest that the rs12435998 SNP in SEL1L gene plays a role in modifying age at diagnosis of PDA in Caucasian nonsmokers. In addition, this SNP may serve as a prognostic marker in PDA patients who undergo the same or similar treatment as the clinical trials. (c) 2011 Wiley Periodicals, Inc.
引用
收藏
页码:433 / 438
页数:6
相关论文
共 33 条
  • [1] A Single Nucleotide Polymorphism in Tumor Suppressor Gene SEL1L as Predictive and Prognostic Marker for Pancreatic Ductal Adenocarcinoma
    Liu, Q.
    Chen, J.
    Mai, B.
    Amos, C.
    Killary, A. M.
    Sen, S.
    Frazier, M. L.
    PANCREAS, 2010, 39 (08) : 1330 - 1331
  • [2] Putative Tumor Suppressor Gene SEL1L Was Downregulated by Aberrantly Upregulated hsa-mir-155 in Human Pancreatic Ductal Adenocarcinoma
    Liu, Qian
    Chen, Jinyun
    Wang, Jin
    Amos, Christopher
    Killary, Ann M.
    Sen, Subrata
    Wei, Chongjuan
    Frazier, Marsha L.
    MOLECULAR CARCINOGENESIS, 2014, 53 (09) : 711 - 721
  • [3] The utility of PD-L1 as a prognostic marker in pancreatic ductal adenocarcinoma (PDAC).
    Wu, Linda
    Fulop, Daniel Jeremy
    Rudshteyn, Michelle
    Shah, Nagma
    Hill-Oliva, Michael
    Sohval, Sophie
    Gandhi, Sonal
    Chowdhury, Nobel
    Debnath, Neha
    Cohen, Deirdre Jill
    JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 : 753 - 753
  • [4] Characterization of pancreatic ductal adenocarcinoma using whole transcriptome sequencing and copy number analysis by single-nucleotide polymorphism array
    Di Marco, Mariacristina
    Astolfi, Annalisa
    Grassi, Elisa
    Vecchiarelli, Silvia
    Macchini, Marina
    Indio, Valentina
    Casadei, Riccardo
    Ricci, Claudio
    D'Ambra, Marielda
    Taffurelli, Giovanni
    Serra, Carla
    Ercolani, Giorgio
    Santini, Donatella
    D'Errico, Antonia
    Pinna, Antonio Daniele
    Minni, Francesco
    Durante, Sandra
    Martella, Laura Raffaella
    Biasco, Guido
    MOLECULAR MEDICINE REPORTS, 2015, 12 (05) : 7479 - 7484
  • [5] SEL1L expression in pancreatic adenocarcinoma parallels SMAD4 expression and delays tumor growth in vitro and in vivo
    Monica Cattaneo
    Simonetta Orlandini
    Stefania Beghelli
    Patrick S Moore
    Claudio Sorio
    Antonio Bonora
    Claudio Bassi
    Giorgio Talamini
    Giuseppe Zamboni
    Rosaria Orlandi
    Sylvie Ménard
    Luigi Rossi Bernardi
    Ida Biunno
    Aldo Scarpa
    Oncogene, 2003, 22 : 6359 - 6368
  • [6] EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through β-catenin/ID2 pathway
    Mo, Shi-Jing
    Liu, Xin
    Hao, Xiao-Yi
    Chen, Wei
    Zhang, Kun-Song
    Cai, Jian-Peng
    Lai, Jia-Ming
    Liang, Li-Jian
    Yin, Xiao-Yu
    CANCER LETTERS, 2016, 380 (02) : 403 - 412
  • [7] SEL1L expression in pancreatic adenocarcinoma parallels SMAD4 expression and delays tumor growth in vitro and in vivo
    Cattaneo, M
    Orlandini, S
    Beghelli, S
    Moore, PS
    Sorio, C
    Bonora, A
    Bassi, C
    Talamini, G
    Zamboni, G
    Orlandi, R
    Ménard, S
    Bernardi, LR
    Biunno, I
    Scarpa, A
    ONCOGENE, 2003, 22 (41) : 6359 - 6368
  • [8] The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1
    Krupenko, Sergey A.
    Horita, David A.
    FRONTIERS IN GENETICS, 2019, 10
  • [9] Prognostic Value of the Preoperative Tumor Marker Index in Resected Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Institution Study
    Miyata, Tatsunori
    Hayashi, Hiromitsu
    Yamashita, Yo-ichi
    Matsumura, Kazuki
    Nakao, Yosuke
    Itoyama, Rumi
    Yamao, Takanobu
    Tsukamoto, Masayo
    Okabe, Hirohisa
    Imai, Katsunori
    Chikamoto, Akira
    Ishiko, Takatoshi
    Baba, Hideo
    ANNALS OF SURGICAL ONCOLOGY, 2021, 28 (03) : 1572 - 1580
  • [10] Inherent Single Nucleotide Variants in the TBX21 Gene As Novel Prognostic Markers in Patients With Pancreatic Ductal Adenocarcinoma
    Fuji, Tomokazu
    Umeda, Yuzo
    Nagasaka, Takeshi
    Taniguchi, Fumitaka
    Takehara, Yuko
    Kawai, Takashi
    Kimura, Keisuke
    Toshima, Toshiaki
    Yagi, Takahito
    Goel, Ajay
    Fujiwara, Toshiyoshi
    GASTROENTEROLOGY, 2015, 148 (04) : S392 - S392