High expression of AFAP1-AS1 is associated with poor survival and short-term recurrence in pancreatic ductal adenocarcinoma.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is still a lethal malignancy. Long noncoding RNAs (lncRNAs) have been shown to play a critical role in cancer development and progression. Here we identified overexpression of the lncRNA AFAP1-AS1 in PDAC patients and evaluated its prognostic and functional relevance.


METHODS
The global lncRNA expression profile in PDAC was measured by lncRNA microarray. Expression of AFAP1-AS1 was evaluated by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) in 90 PDAC tissue samples and adjacent normal tissues. The impact of AFAP1-AS1 expression on cell proliferation, migration, and invasion were evaluated in vitro using knockdown and ectopic expression strategies.


RESULTS
Microarray analysis revealed that up-regulation of AFAP1-AS1 expression in PDAC tissues compared with normal adjacent tissues, which was confirmed by RT-qPCR in 69/90 cases (76.7%). Its overexpression was associated with lymph node metastasis, perineural invasion, and poor survival. When using AFAP1-AS1 as a prognostic marker, the areas under ROC curves were 0.8669 and 0.9370 for predicting tumor progression within 6 months and 1 year, respectively. In vitro functional experiments involving knockdown of AFAP1-AS1 resulted in attenuated PDAC cell proliferation, migration, and invasion. Ectopic expression of AFAP1-AS1 promoted cell proliferation, migration, and invasion.


CONCLUSIONS
AFAP1-AS1 is a potential novel prognostic marker to predict the clinical outcome of PDAC patients after surgery and may be a rational target for therapy.
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. kkbiao@163.com.
Yibiao
Y
Ye
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Chenj_sysu@126.com.
Jie
J
Chen
Department of Pancreaticobiliary Surgery, Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. zyzysmile@163.com.|Present Address: Department of General Surgery, Guangdong General Hospital, Guangzhou, China. zyzysmile@163.com.
Yu
Y
Zhou
Department of Pancreaticobiliary Surgery, Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. fzhiqiang_sysu@126.com.
Zhiqiang
Z
Fu
Department of Pancreaticobiliary Surgery, Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. zhquanbo@126.com.
Quanbo
Q
Zhou
Department of Pancreaticobiliary Surgery, Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. wyingxue_sysu@126.com.
YingXue
Y
Wang
Department of Pancreaticobiliary Surgery, Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. gwenchao_sysu@126.com.
Wenchao
W
Gao
Department of Pancreaticobiliary Surgery, Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. zhshangyou_sysu@126.com.
ShangYou
S
Zheng
Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. zhxiaohui_sysu@126.com.
Xiaohui
X
Zhao
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. chent_sysu@163.com.
Tao
T
Chen
Department of Pancreaticobiliary Surgery, Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. chent_sysu@163.com.|Department of General Surgery, The Second Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, 107 Yan-Jiang Xi Road, Guangzhou, 510120, China. chent_sysu@163.com.
Rufu
R
Chen
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors
C000605367:AFAP1-AS1 long noncoding RNA, human; D062085:RNA, Long Noncoding