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Erschienen in: Pathology & Oncology Research 3/2020

20.08.2019 | Original Article

Hsa_circ_0065149 is an Indicator for Early Gastric Cancer Screening and Prognosis Prediction

verfasst von: Yongfu Shao, Xueping Tao, Rongdan Lu, Haiqiang Zhang, Jiaxin Ge, Bingxiu Xiao, Guoliang Ye, Junming Guo

Erschienen in: Pathology & Oncology Research | Ausgabe 3/2020

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Abstract

Circular RNAs (circRNAs) are an endogenous RNAs with a covalently closed cyclic structure. They have emerged recently as key regulators in the development and progression of human cancers. However, the clinical values of most circRNAs in gastric cancer (GC) are unknown. Hsa_circ_0065149, one of the dysregulated circRNAs in gastric carcinogenesis detected by circRNA microarray, was chose as a targeted circRNA in this study. We firstly enlarged sample size and identified the level changes of hsa_circ_0065149 among four stages of gastric tumorigenesis from healthy gastric mucosa, gastritis, intestinal metaplasia to GC. Then, the potential relationship between hsa_circ_0065149 expression levels and GC patients’ clinicopathological factors was investigated. Moreover, the clinical significance of hsa_circ_0065149 in plasma exosomes and gastric juice were explored. Receiver operating characteristic (ROC) curve and Kaplan-Meier survival curve were constructed to evaluate diagnostic and prognostic values. Finally, bioinformatics analysis was performed to excavate the potential functions of hsa_circ_0065149. Hsa_circ_0065149 expression was only significantly down-regulated in gastric cancer, not changed among healthy gastric mucosa and gastritis intestinal metaplasia. Low hsa_circ_0065149 expression levels in GC tissues were significantly associated with tumor diameter (P = 0.034) and perineural invasion (P = 0.037). GC patients with low hsa_circ_0065149 levels had a much longer overall survival than those in high group (P = 0.020). More important, hsa_circ_0065149 levels were significantly decreased in plasma exosomes of early GC patients. As a screening biomarker for early GC, hsa_circ_0065149 in plasma exosomes has higher sensitivity and specificity than traditional clinical biomarkers. Bioinformatics analysis suggest that the abnormal expression of hsa_circ_0065149 may play an important role during gastric carcinogenesis. Those results indicate that hsa_circ_0065149 in exosmoes is an indicator for early GC screening and prognosis prediction.
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Literatur
1.
Zurück zum Zitat Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(4):7–30CrossRef Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(4):7–30CrossRef
2.
Zurück zum Zitat Tian M, Chen R, Li T, Xiao B (2018) Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance. J Clin Lab Anal 32(3):e22281CrossRef Tian M, Chen R, Li T, Xiao B (2018) Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance. J Clin Lab Anal 32(3):e22281CrossRef
3.
Zurück zum Zitat Wang J, Qu J, Li Z, Che X, Liu J, Teng Y, Jin B, Zhao M, Liu Y, Qu X (2018) Pretreatment platelet-to-lymphocyte ratio is associated with the response to first-line chemotherapy and survival in patients with metastatic gastric cancer. J Clin Lab Anal 32(3):e22185CrossRef Wang J, Qu J, Li Z, Che X, Liu J, Teng Y, Jin B, Zhao M, Liu Y, Qu X (2018) Pretreatment platelet-to-lymphocyte ratio is associated with the response to first-line chemotherapy and survival in patients with metastatic gastric cancer. J Clin Lab Anal 32(3):e22185CrossRef
4.
Zurück zum Zitat Xie Y, Shao Y, Sun W, Ye G, Zhang X, Xiao B, Guo J (2018) Downregulated expression of hsa_circ_0074362 in gastric cancer and its potential diagnostic values. Biomark Med 12(1):11–20CrossRef Xie Y, Shao Y, Sun W, Ye G, Zhang X, Xiao B, Guo J (2018) Downregulated expression of hsa_circ_0074362 in gastric cancer and its potential diagnostic values. Biomark Med 12(1):11–20CrossRef
5.
Zurück zum Zitat Salzman J (2016) Circular RNA expression: its potential regulation and function. Trends Genet 32(5):309–316CrossRef Salzman J (2016) Circular RNA expression: its potential regulation and function. Trends Genet 32(5):309–316CrossRef
6.
Zurück zum Zitat Zhang Y, Liang W, Zhang P, Chen J, Qian H, Zhang X, Xu W (2017) Circular RNAs: emerging cancer biomarkers and targets. J Exp Clin Cancer Res 36(1):152CrossRef Zhang Y, Liang W, Zhang P, Chen J, Qian H, Zhang X, Xu W (2017) Circular RNAs: emerging cancer biomarkers and targets. J Exp Clin Cancer Res 36(1):152CrossRef
8.
Zurück zum Zitat Qu S, Liu Z, Yang X, Zhou J, Yu H, Zhang R, Li H (2018) The emerging functions and roles of circular RNAs in cancer. Cancer Lett 414:301–309CrossRef Qu S, Liu Z, Yang X, Zhou J, Yu H, Zhang R, Li H (2018) The emerging functions and roles of circular RNAs in cancer. Cancer Lett 414:301–309CrossRef
9.
Zurück zum Zitat Kristensen LS, Hansen TB, Venø MT, Kjems J (2018) Circular RNAs in cancer: opportunities and challenges in the field. Oncogene 37(5):555–565CrossRef Kristensen LS, Hansen TB, Venø MT, Kjems J (2018) Circular RNAs in cancer: opportunities and challenges in the field. Oncogene 37(5):555–565CrossRef
10.
Zurück zum Zitat Shao Y, Li J, Lu R, Li T, Yang Y, Xiao B, Guo J (2017) Global circular RNA expression profile of human gastric cancer and its clinical significance. Can Med 6(6):1173–1180CrossRef Shao Y, Li J, Lu R, Li T, Yang Y, Xiao B, Guo J (2017) Global circular RNA expression profile of human gastric cancer and its clinical significance. Can Med 6(6):1173–1180CrossRef
11.
Zurück zum Zitat Yu Z, Wei L, Peng Z, Chen J, Qian H, Zhang X, Xu W (2017) Circular RNAs: emerging cancer biomarkers and targets. J Exp Clin Cancer Res 36(1):152CrossRef Yu Z, Wei L, Peng Z, Chen J, Qian H, Zhang X, Xu W (2017) Circular RNAs: emerging cancer biomarkers and targets. J Exp Clin Cancer Res 36(1):152CrossRef
12.
Zurück zum Zitat Li H, Hao X, Wang H, Liu Z, He Y, Pu M, Zhang H, Yu H, Duan J, Qu S (2016) Circular RNA expression profile of pancreatic ductal adenocarcinoma revealed by microarray. Cell Physiol Biochem 40(6):1334–1344CrossRef Li H, Hao X, Wang H, Liu Z, He Y, Pu M, Zhang H, Yu H, Duan J, Qu S (2016) Circular RNA expression profile of pancreatic ductal adenocarcinoma revealed by microarray. Cell Physiol Biochem 40(6):1334–1344CrossRef
13.
Zurück zum Zitat Fu L, Yao T, Chen Q, Mo X, Hu Y, Guo J (2017) Screening differential circular rna expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma. Oncotarget 8(35):58405–58416CrossRef Fu L, Yao T, Chen Q, Mo X, Hu Y, Guo J (2017) Screening differential circular rna expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma. Oncotarget 8(35):58405–58416CrossRef
14.
Zurück zum Zitat Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T, Dalamagas T, Hatzigeorgiou AG (2015) DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res 43(1):460–466CrossRef Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T, Dalamagas T, Hatzigeorgiou AG (2015) DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res 43(1):460–466CrossRef
15.
Zurück zum Zitat Liu J, Liu T, Wang X, He A (2017) Circles reshaping the RNA world: from waste to treasure. Mol Cancer 16(1):58CrossRef Liu J, Liu T, Wang X, He A (2017) Circles reshaping the RNA world: from waste to treasure. Mol Cancer 16(1):58CrossRef
16.
Zurück zum Zitat Zhang Y, Liu H, Li W, Yu J, Li J, Shen Z, Ye G, Qi X, Li G (2017) CircRNA_100269 is downregulated in gastric cancer and suppresses tumor cell growth by targeting miR-630. Aging 9(6):1585–1594CrossRef Zhang Y, Liu H, Li W, Yu J, Li J, Shen Z, Ye G, Qi X, Li G (2017) CircRNA_100269 is downregulated in gastric cancer and suppresses tumor cell growth by targeting miR-630. Aging 9(6):1585–1594CrossRef
17.
Zurück zum Zitat Li T, Shao Y, Fu L, Xie Y, Zhu L, Sun W, Yu R, Xiao B, Guo J (2018) Plasma circular RNA profiling of patients with gastric cancer and their droplet digital RT-PCR detection. J Mol Med 96(1):85–96CrossRef Li T, Shao Y, Fu L, Xie Y, Zhu L, Sun W, Yu R, Xiao B, Guo J (2018) Plasma circular RNA profiling of patients with gastric cancer and their droplet digital RT-PCR detection. J Mol Med 96(1):85–96CrossRef
18.
Zurück zum Zitat Wang H, Huang C, Zheng C, Li P, Xie W, Wang J, Lin J, Lu J (2012) Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach. World J Gastroenterol 18(38):5470–5475CrossRef Wang H, Huang C, Zheng C, Li P, Xie W, Wang J, Lin J, Lu J (2012) Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach. World J Gastroenterol 18(38):5470–5475CrossRef
19.
Zurück zum Zitat Deng J, You Q, Gao Y, Yu Q, Zhao P, Zheng Y, Fang W, Xu N, Teng L (2014) Prognostic value of perineural invasion in gastric cancer: a systematic review and meta-analysis. PLoS One 9(2):e88907CrossRef Deng J, You Q, Gao Y, Yu Q, Zhao P, Zheng Y, Fang W, Xu N, Teng L (2014) Prognostic value of perineural invasion in gastric cancer: a systematic review and meta-analysis. PLoS One 9(2):e88907CrossRef
20.
Zurück zum Zitat Lu J, Huang C, Zheng C, Li P, Xie J, Wang J, Lin J (2013) Consideration of tumor size improves the accuracy of TNM predictions in patients with gastric cancer after curative gastrectomy. Surg Oncol 22(3):167–171CrossRef Lu J, Huang C, Zheng C, Li P, Xie J, Wang J, Lin J (2013) Consideration of tumor size improves the accuracy of TNM predictions in patients with gastric cancer after curative gastrectomy. Surg Oncol 22(3):167–171CrossRef
21.
Zurück zum Zitat Lu J, Huang C, Zheng C, Li P, Xie J, Wang J, Lin J, Chen Q, Cao L, Lin M (2014) Prognostic value of tumor size in patients with remnant gastric cancer: is the seventh UICC stage sufficient for predicting prognosis? PLoS One 9(12):e115776CrossRef Lu J, Huang C, Zheng C, Li P, Xie J, Wang J, Lin J, Chen Q, Cao L, Lin M (2014) Prognostic value of tumor size in patients with remnant gastric cancer: is the seventh UICC stage sufficient for predicting prognosis? PLoS One 9(12):e115776CrossRef
22.
Zurück zum Zitat Zhou Z, Xu G, Zhang W, Zhao H, Wu Y (2014) Reevaluating significance of perineural invasion in gastric cancer based on double immunohistochemical staining. Arch Pathol Lab Med 138(2):229–234CrossRef Zhou Z, Xu G, Zhang W, Zhao H, Wu Y (2014) Reevaluating significance of perineural invasion in gastric cancer based on double immunohistochemical staining. Arch Pathol Lab Med 138(2):229–234CrossRef
23.
Zurück zum Zitat Fan F, Tian Y, Xu G, Liu Z, Liu S, Zheng G, Guo M, Lian X, Fan D, Zhang H (2017) Diagnostic and prognostic value of CEA, CA19–9, AFP and CA125 for early gastric cancer. BMC Cancer 17(1):737CrossRef Fan F, Tian Y, Xu G, Liu Z, Liu S, Zheng G, Guo M, Lian X, Fan D, Zhang H (2017) Diagnostic and prognostic value of CEA, CA19–9, AFP and CA125 for early gastric cancer. BMC Cancer 17(1):737CrossRef
24.
Zurück zum Zitat Whiteside TL (2015) The potential of tumor-derived exosomes for noninvasive cancer monitoring. Expert Rev Mol Diagn 15(10):1293–1310CrossRef Whiteside TL (2015) The potential of tumor-derived exosomes for noninvasive cancer monitoring. Expert Rev Mol Diagn 15(10):1293–1310CrossRef
25.
Zurück zum Zitat Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W (2015) Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol 40:72–81CrossRef Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W (2015) Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol 40:72–81CrossRef
26.
Zurück zum Zitat Fernando MR, Jiang C, Krzyzanowski GD, Ryan WL (2017) New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes. PLoS One 12(8):e0183915CrossRef Fernando MR, Jiang C, Krzyzanowski GD, Ryan WL (2017) New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes. PLoS One 12(8):e0183915CrossRef
27.
Zurück zum Zitat Cui L, Zhang X, Ye G, Zheng T, Song H, Deng H, Xiao B, Xia T, Yu X, Le Y, Guo J (2013) Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer. Cancer 119(9):1618–1626CrossRef Cui L, Zhang X, Ye G, Zheng T, Song H, Deng H, Xiao B, Xia T, Yu X, Le Y, Guo J (2013) Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer. Cancer 119(9):1618–1626CrossRef
28.
Zurück zum Zitat Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, Tang W, Cao H (2017) An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget 8(42):73271–73281CrossRef Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, Tang W, Cao H (2017) An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget 8(42):73271–73281CrossRef
29.
Zurück zum Zitat Cheng J, Zhuo H, Xu M, Wang L, Xu H, Peng J, Hou J, Lin L, Cai J (2018) Regulatory network of circRNA-miRNA-mRNA contributes to the histological classification and disease progression in gastric cancer. J Transl Med 16(1):216CrossRef Cheng J, Zhuo H, Xu M, Wang L, Xu H, Peng J, Hou J, Lin L, Cai J (2018) Regulatory network of circRNA-miRNA-mRNA contributes to the histological classification and disease progression in gastric cancer. J Transl Med 16(1):216CrossRef
Metadaten
Titel
Hsa_circ_0065149 is an Indicator for Early Gastric Cancer Screening and Prognosis Prediction
verfasst von
Yongfu Shao
Xueping Tao
Rongdan Lu
Haiqiang Zhang
Jiaxin Ge
Bingxiu Xiao
Guoliang Ye
Junming Guo
Publikationsdatum
20.08.2019
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 3/2020
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-019-00716-y

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