长链非编码RNA POU6F2-AS2在人胃癌组织中的表达及临床意义
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摘要
目的探讨长链非编码RNA POU6F2-AS2在人胃癌组织中的表达及临床意义。方法收集2017年5月至2018年5月期间川北医学院附属医院普外科收治的73例行胃癌根治手术患者的胃癌组织及其配对的距离癌组织5 cm处的癌旁胃黏膜组织标本,采用实时荧光定量聚合酶链反应方法检测胃癌组织及其相对应的癌旁组织中POU6F2-AS2表达水平,采用χ2检验分析其表达水平与胃癌患者临床病理特征的关系,通过Kaplan Meier Plotter数据库数据分析POU6F2-AS2的表达与胃癌患者总体生存率的关系。结果胃癌组织中POU6F2-AS2相对表达量明显高于其对应的癌旁组织(P<0.050)。根据胃癌组织与其对应的癌旁组织中POU6F2-AS2表达水平将POU6F2-AS2在癌组织中高于其癌旁组织的病例归为高表达(43例),反之归为低表达组(30例)。分析POU6F2-AS2表达高低与胃癌患者临床病理特征的关系发现,POU6F2-AS2高表达与肿瘤浸润深度(P=0.022)和TNM分期(P=0.032)有关,而与胃癌患者的性别、年龄、是否吸烟、是否饮酒、肿瘤直径、分化程度、淋巴结转移、远处转移、脉管浸润、神经浸润、肝脏转移、有无腹水及脂肪结节是否转移均无关(P>0.050)。通过Kaplan Meier Plotter数据库数据分析631例胃癌患者POU6F2-AS2表达水平与患者总体生存率的关系发现,POU6F2-AS2高表达组相对于其低表达组预后更差(P=0.001)。结论 POU6F2-AS2高表达与肿瘤浸润深度和TNM分期有关,其可能参与了调控胃癌的发生及发展,有希望作为潜在的胃癌基因诊断和治疗的重要靶点以及评估胃癌患者预后的生物标志物。
Objective To investigate expression and clinical significance of long chain noncoding RNA POU6 F2-AS2 in human gastric cancer tissues. Methods Seventy-three pairs of human gastric cancer and matched paracancerous tissues from May 2017 to May 2018 in the Affiliated Hospital of North Sichuan Medical College were collected. The realtime fluorescence quantitative polymerase chain reaction was used to detect the expression level of POU6 F2-AS2 in the gastric cancer tissue and its paracancerous tissue. The correlations between its expression level and clinicalpathologic features of patients were analyzed by the chi-square text. The relationship between the expression of POU6F2-AS2 and the overall survival rate of patient with gastric cancer was analyzed by the Kaplan Meier Plotter database data. Results The relative expression of POU6F2-AS2 in the gastric cancer tissues was significantly higher than that in the corresponding adjacent tissues(P<0.050). The patients were divided into the high expression(43 cases) and low expression group(30 cases) according to the expression level of POU6F2-AS2 in the gastric cancer tissues and their corresponding adjacent tissues. The results of the relationship between the expression of POU6F2-AS2 and the clinicopathologic characteristics of patients with gastric cancer showed that the POU6F2-AS2 expression was significantly correlated with the depth of invasion(P=0.022) or the TNM stage(P=0.032). There were no significant differences in the gender, age, smoking history,drinking history, tumor diameter, degree of differentiation, lymph node metastasis, distant metastasis, vascular invasion,nerve invasion, liver metastasis, ascites, and fat nodule metastasis(P>0.050). The overall survival rate of high expression of POU6F2-AS2 in the patient with gastric cancer was significantly worse than that of the low expression of POU6F2-AS2 by the Kaplan Meier Plotter database. Conclusions High expression of POU6F2-AS2 is related to depth of tumor invasion and TNM stage, which indicates that POU6 F2-AS2 might play an important role in regulating occurrence and development of gastric cancer. It may be used as an important target for gene diagnosis and treatment of gastric cancer and as a biomarker for evaluating prognosis of patients with gastric cancer.
Objective To investigate expression and clinical significance of long chain noncoding RNA POU6 F2-AS2 in human gastric cancer tissues. Methods Seventy-three pairs of human gastric cancer and matched paracancerous tissues from May 2017 to May 2018 in the Affiliated Hospital of North Sichuan Medical College were collected. The realtime fluorescence quantitative polymerase chain reaction was used to detect the expression level of POU6 F2-AS2 in the gastric cancer tissue and its paracancerous tissue. The correlations between its expression level and clinicalpathologic features of patients were analyzed by the chi-square text. The relationship between the expression of POU6F2-AS2 and the overall survival rate of patient with gastric cancer was analyzed by the Kaplan Meier Plotter database data. Results The relative expression of POU6F2-AS2 in the gastric cancer tissues was significantly higher than that in the corresponding adjacent tissues(P<0.050). The patients were divided into the high expression(43 cases) and low expression group(30 cases) according to the expression level of POU6F2-AS2 in the gastric cancer tissues and their corresponding adjacent tissues. The results of the relationship between the expression of POU6F2-AS2 and the clinicopathologic characteristics of patients with gastric cancer showed that the POU6F2-AS2 expression was significantly correlated with the depth of invasion(P=0.022) or the TNM stage(P=0.032). There were no significant differences in the gender, age, smoking history,drinking history, tumor diameter, degree of differentiation, lymph node metastasis, distant metastasis, vascular invasion,nerve invasion, liver metastasis, ascites, and fat nodule metastasis(P>0.050). The overall survival rate of high expression of POU6F2-AS2 in the patient with gastric cancer was significantly worse than that of the low expression of POU6F2-AS2 by the Kaplan Meier Plotter database. Conclusions High expression of POU6F2-AS2 is related to depth of tumor invasion and TNM stage, which indicates that POU6 F2-AS2 might play an important role in regulating occurrence and development of gastric cancer. It may be used as an important target for gene diagnosis and treatment of gastric cancer and as a biomarker for evaluating prognosis of patients with gastric cancer.
引文
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2 Chen W, Zheng R, Baade PD, et al. Cancer statistics in China,2015. CA Cancer J Clin, 2016, 66(2):115-132.
3 Van Cutsem E, Sagaert X, Topal B, et al. Gastric cancer. Lancet,2016, 388(10060):2654-2664.
4 Yamaguchi K, Yoshida K, Tanahashi T, et al.The long-term survival of stageⅣgastric cancer patients with conversion therapy.Gastric Cancer, 2018,21(2):315-323.
5 Beermann J, Piccoli MT, Viereck J, et al. Non-coding RNAs in development and disease:background, mechanisms, and therapeutic approaches. Physiol Rev, 2016, 96(4):1297-1325.
6 Wu H, Yang L, Chen LL. The diversity of long noncoding RNAs and their generation. Trends Genet, 2017, 33(8):540-552.
7马英博,张小东,杨照国,等.lncRNA调控肿瘤能量代谢机制的研究进展.中国普外基础与临床杂志,2017, 24(3):381-385.
8 Sun TT, He J, Liang Q, et al. LncRNA GClncl promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 andKAT2A complexes to specify the histone modification pattern.Cancer Discov, 2016,6(7):784-801.
9 Xiao ZD, Han L, Lee H, et al. Energy stress-induced IncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development. Nat Commun, 2017, 8(1):783.
10 Zhang J, Li Z, Liu L, et al. Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3signaling pathway. Hepatology, 2018, 67(1):171-187.
11 Zhuo W, Liu Y, Li S, et al. Long noncoding RNA GMAN, upregulated in gastric cancer tissues, is associated with metastasis in patients and promotes translation of Ephrin A1 by competitively binding GMAN-AS. Gastroenterology, 2019,156(3):676-691.
12张麒,艾良,代佑果.长链非编码RNA母系表达基因3多态性与胃癌关系的研究.中国普外基础与临床杂志,2018, 25(11):1323-1326.
13 Washington K. 7th edition of the AJCC cancer staging manual:stomach. Ann Surg Oncol, 2010, 17(12):3077-3079.
14 Edge SB, Compton CC. The American Joint Committee on Cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010,17(6):1471-1474.
15 Schefe JH, Lehmann KE, Buschmann IR, et al. Quantitative realtime RT-PCR data analysis:current concepts and the novel"gene expression's CT difference"formula. J Mol Med(Berl),2006,84(11):901-910.
16 Huarte M. The emerging role of lncRNAs in cancer. Nat Med,2015,21(11):1253-1261.
17 Marchese FP, Raimondi I, Huarte M. The multidimensional mechanisms of long noncoding RNA function. Genome Biol, 2017,18(1):206.
18 Kopp F, Mendell JT. Functional classification and experimental dissection of long noncoding RNAs. Cell, 2018, 172(3):393-407.
19 Zeng S, Xie X, Xiao YF, et al. Long noncoding RNA LINC00675enhances phosphorylation of vimentin on Ser83 to suppress gastric cancer progression. Cancer Lett, 2018,412:179-187.
20 Yang XZ, Cheng TT, He QJ, et al. LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway. Mol Cancer,2018,17(1):126.
21 Zhang X, Liang W, Liu J, et al. Long non-coding RNA UFC1promotes gastric cancer progression by regulating miR-498/Lin28b. J Exp Clin Cancer Res, 2018, 37(1):134.
22 Zhao R, Zhang Y, Zhang X, et al. Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer. Mol Cancer, 2018,17(1):68.
23 Liu J, Sun X, Zhu H, et al. Long noncoding RNA POU6F2-AS2 is associated with oesophageal squamous cell carcinoma. J Biochem,2016,160(4):195-204.
24 Luo Y, Tan W, Jia W, et al. The long non-coding RNA LINC01606contributes to the metastasis and invasion of human gastric cancer and is associated with Wnt/β-catenin signaling. Int J Biochem Cell Biol,2018, 103:125-134.
25 Luo Y, Wang C, Yong P, et al. Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor prognosis and promotes tumor growth in gastric cancer. Oncotarget, 2017, 8(68):112530-112549.
2 Chen W, Zheng R, Baade PD, et al. Cancer statistics in China,2015. CA Cancer J Clin, 2016, 66(2):115-132.
3 Van Cutsem E, Sagaert X, Topal B, et al. Gastric cancer. Lancet,2016, 388(10060):2654-2664.
4 Yamaguchi K, Yoshida K, Tanahashi T, et al.The long-term survival of stageⅣgastric cancer patients with conversion therapy.Gastric Cancer, 2018,21(2):315-323.
5 Beermann J, Piccoli MT, Viereck J, et al. Non-coding RNAs in development and disease:background, mechanisms, and therapeutic approaches. Physiol Rev, 2016, 96(4):1297-1325.
6 Wu H, Yang L, Chen LL. The diversity of long noncoding RNAs and their generation. Trends Genet, 2017, 33(8):540-552.
7马英博,张小东,杨照国,等.lncRNA调控肿瘤能量代谢机制的研究进展.中国普外基础与临床杂志,2017, 24(3):381-385.
8 Sun TT, He J, Liang Q, et al. LncRNA GClncl promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 andKAT2A complexes to specify the histone modification pattern.Cancer Discov, 2016,6(7):784-801.
9 Xiao ZD, Han L, Lee H, et al. Energy stress-induced IncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development. Nat Commun, 2017, 8(1):783.
10 Zhang J, Li Z, Liu L, et al. Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3signaling pathway. Hepatology, 2018, 67(1):171-187.
11 Zhuo W, Liu Y, Li S, et al. Long noncoding RNA GMAN, upregulated in gastric cancer tissues, is associated with metastasis in patients and promotes translation of Ephrin A1 by competitively binding GMAN-AS. Gastroenterology, 2019,156(3):676-691.
12张麒,艾良,代佑果.长链非编码RNA母系表达基因3多态性与胃癌关系的研究.中国普外基础与临床杂志,2018, 25(11):1323-1326.
13 Washington K. 7th edition of the AJCC cancer staging manual:stomach. Ann Surg Oncol, 2010, 17(12):3077-3079.
14 Edge SB, Compton CC. The American Joint Committee on Cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010,17(6):1471-1474.
15 Schefe JH, Lehmann KE, Buschmann IR, et al. Quantitative realtime RT-PCR data analysis:current concepts and the novel"gene expression's CT difference"formula. J Mol Med(Berl),2006,84(11):901-910.
16 Huarte M. The emerging role of lncRNAs in cancer. Nat Med,2015,21(11):1253-1261.
17 Marchese FP, Raimondi I, Huarte M. The multidimensional mechanisms of long noncoding RNA function. Genome Biol, 2017,18(1):206.
18 Kopp F, Mendell JT. Functional classification and experimental dissection of long noncoding RNAs. Cell, 2018, 172(3):393-407.
19 Zeng S, Xie X, Xiao YF, et al. Long noncoding RNA LINC00675enhances phosphorylation of vimentin on Ser83 to suppress gastric cancer progression. Cancer Lett, 2018,412:179-187.
20 Yang XZ, Cheng TT, He QJ, et al. LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway. Mol Cancer,2018,17(1):126.
21 Zhang X, Liang W, Liu J, et al. Long non-coding RNA UFC1promotes gastric cancer progression by regulating miR-498/Lin28b. J Exp Clin Cancer Res, 2018, 37(1):134.
22 Zhao R, Zhang Y, Zhang X, et al. Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer. Mol Cancer, 2018,17(1):68.
23 Liu J, Sun X, Zhu H, et al. Long noncoding RNA POU6F2-AS2 is associated with oesophageal squamous cell carcinoma. J Biochem,2016,160(4):195-204.
24 Luo Y, Tan W, Jia W, et al. The long non-coding RNA LINC01606contributes to the metastasis and invasion of human gastric cancer and is associated with Wnt/β-catenin signaling. Int J Biochem Cell Biol,2018, 103:125-134.
25 Luo Y, Wang C, Yong P, et al. Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor prognosis and promotes tumor growth in gastric cancer. Oncotarget, 2017, 8(68):112530-112549.