LASS2在鼻咽癌中的表达及其意义
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摘要
目的:探讨LASS2在鼻咽癌(nasopharyngeal carcinoma,NPC)的发生与发展中的作用。方法:收集2011年6月至2014年12月佛山市顺德区中医院治疗并随访的Ⅰ~Ⅳ期鼻咽癌病例127例,其中鼻咽癌Ⅰ期12例(A组),鼻咽癌Ⅱ期26例(B组),鼻咽癌Ⅲ期52例(C组),鼻咽癌Ⅳ期37例(D组),以及慢性鼻咽炎病例49例(E组)。采用免疫组织化学方法检测LASS2蛋白在鼻咽活检组织中的表达。并收集鼻咽癌各组的相关临床资料,分析LASS2表达与各临床因素之间的相关性。结果:LASS2在鼻咽癌病例中的表达率(A,B,C,D组表达的百分率分别是75%,73.1%,78.8%及81.1%)低于慢性鼻咽炎病例中的表达率(E组表达的百分率为100%),其差别具有统计学意义(P=0.008)。LASS2的表达与肿瘤的复发存在负相关性(P=0.001),但LASS2阳性病例与LASS2阴性病例的无瘤生存期的差别无统计学意义(P>0.05)。结论:LASS2是一种抑癌基因,其蛋白产物表达于非肿瘤性的鼻咽组织中。鼻咽癌发生过程中可能发生了蛋白的丢失,从而促进鼻咽癌的发病。LASS2蛋白的丢失与鼻咽癌复发也存在相关性,LASS2可能成为预测鼻咽癌复发的有临床意义的生物学指标。
Objective:To investigate the role of the expression of L ASS2 on the occurrence and development of nasopharyngeal carcinoma(NPC).Methods:A total of 127 cases of NPC in total,including stageⅠ 12 cases(group A),stage Ⅱ 26 cases(group B),stage Ⅲ 52 cases(group C),stage Ⅳ 27 cases(group D),and 49 cases of chronic nasopharyngitis(group E),were collected in our hospital from Jun.2011 to Dec.2014.The expression of LASS2 was evaluated by immunohistochemical.The associations between the expression of LASS2 and the clinicopathological parameters of NPC patients were statistically analyzed.Results:The expression of LASS2 in NPC(from group A to group D were 75%,73.1%,78.8% and 81.1%) were significantly lower than chronic nasopharyngitis(group E was 100%)(P=0.008).Recurrence of NPC was related to low expression of LASS2(P=0.001).However,the disease-free survival in LASS2 positive group was similar to LASS2 negative group(P>0.05).Conclusion:LASS2 is one kind of tumor suppressor gene.Its encoding protein express in non-tumor nasopharyngeal tissues.LASS2 protein may be lost during the occurrence of NPC.Similarly,recurrence of NPC may be related to the loss of LASS2 protein.LASS2 may be a valuable predictor for recurrence of NPC.
Objective:To investigate the role of the expression of L ASS2 on the occurrence and development of nasopharyngeal carcinoma(NPC).Methods:A total of 127 cases of NPC in total,including stageⅠ 12 cases(group A),stage Ⅱ 26 cases(group B),stage Ⅲ 52 cases(group C),stage Ⅳ 27 cases(group D),and 49 cases of chronic nasopharyngitis(group E),were collected in our hospital from Jun.2011 to Dec.2014.The expression of LASS2 was evaluated by immunohistochemical.The associations between the expression of LASS2 and the clinicopathological parameters of NPC patients were statistically analyzed.Results:The expression of LASS2 in NPC(from group A to group D were 75%,73.1%,78.8% and 81.1%) were significantly lower than chronic nasopharyngitis(group E was 100%)(P=0.008).Recurrence of NPC was related to low expression of LASS2(P=0.001).However,the disease-free survival in LASS2 positive group was similar to LASS2 negative group(P>0.05).Conclusion:LASS2 is one kind of tumor suppressor gene.Its encoding protein express in non-tumor nasopharyngeal tissues.LASS2 protein may be lost during the occurrence of NPC.Similarly,recurrence of NPC may be related to the loss of LASS2 protein.LASS2 may be a valuable predictor for recurrence of NPC.
引文
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16 .谭宁,覃文新,万晓桢,等.LASS2基因抑制HCCLM3肝癌细胞的转移[J].肿瘤,2007,27(5):335-340.TAN Ning,QIN Wenxin,WAN Xiaozhen,et al.LASS2 gene inhibits the metastasis of human hepatocellular carcinoma HCCLM3 cells[J].Tumor,2007,27(5):335-340.
17 .Fan S,Niu Y,Tan N,et al.LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump[J].Oncogene,2013,32:1682-1690.
18 .Wang H,Yang D,Wang K,et al.Expression and potential role of chemokine receptor CXCR4 in human bladder carcinoma cell lines with different metastatic ability[J].Mol Med Rep,2011,4(3):525-528.
19 .徐晓艳,由江峰,裴斐,等.RNA沉默LASS2基因促进人前列腺癌细胞体外侵袭及其机制研究[J].北京大学学报(医学版),2011,43(6):814-819.XU Xiaoyan,YOU Jiangfeng,PEI Fei,et al.Silencing of tumor metastasis suppressor gene 1 promotes invasion of prostate cancer cell in vitro and its molecular mechanisms[J].Journal of Peking University.Health Sciences,2011,43(6):814-819.
2 .Liu Z,Li X,He X,et al.Decreased expression of updated NESG1in nasopharyngeal carcinoma:its potential role and preliminarily functional mechanism[J].Int J Cancer,2011,128(11):2562-2571.
3 .Liu Z,Luo W,Zhou Y,et al.Potential tumor suppressor NESG1 as an unfavorable prognosis factor in nasopharyngeal carcinoma[J].PLo S One,2011,6(11):e27887.
4 .方唯意,江庆萍,刘真.蛋白质组学筛选抑癌基因CCDC19在鼻咽癌中的调控蛋白[J].南方医科大学学报,2012,32(8):1127-1130.FANG Weiyi,JIANG Qingping,LIU Zhen.Screening of proteins regulated by CCDC19 gene in nasophar yngeal carcinoma using proteomics technology[J].Journal of Southern Medical University,2012,32(8):1127-1130.
5 .Liu Z,Li L,Yang Z,et al.Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma[J].BMC Cancer,2010,10:270.
6 .Tu L,Liu Z,He X,et al.Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma[J].Mol Cancer,2010,9:78.
7 .涂露霞,方唯意,刘真,等.慢病毒介导的si RNA靶向干扰EIF41鼻咽癌稳定细胞株的建立[J].南方医科大学学报,2009,29(5):844-847.TU Luxia,FANG Weiyi,LIU Zhen,et al.Establishment of a stable nasopharyngeal carcinoma cell line with lent virus-mediated RNA interference for EIF4G1 gene silencing[J].Journal of Southern Medical University,2009,29(5):844-847.
8 .Pan H,Qin WX,Huo KK,et al.Cloning,mapping,and characterization of a human homologue of the yeast longevity assurance gene LAG1[J].Genomics,2001,77(1/2):58-64.
9 .裴斐,由江峰,宁钧宇,等.人肿瘤转移抑制基因TMSG-1单克隆抗体的制备、鉴定及在肿瘤检验中的应用[J].中华病理学杂志,2005,34(1):15-21.PEI Fei,YOU Jiangfeng,NING Junyu,et al.Monoclonal antibodies against human tumor metastasis suppressor gene-1(TMSG-1):preparation,characterization and application[J].Chinese Journal of Pathology,2005,34(1):15-21.
10 .王艳艳,高立勇,赵跃华,等.CERS2基因在浸润性乳腺癌组织中的表达[J].中华病理学杂志,2013,42(4):267-268.WANG Yanyan,GAO Liyong,ZHAO Yuehua,et al.Expression of CERS2 gene in invasive breast cancer[J].Chinese Journal of Pathology,2013,42(4):267-268.
11 .刘奕龙,曹卡加,马国胜,等.广州市鼻咽癌发病率和死亡率分析[J].中国肿瘤,2008,17(7):563-564.LIU Yilong,CAO Kajia,MA Guosheng,et al.An analysis of incidence and mortality of nasophar yngeal cancer in Guangzhou City[J].Chinese Cancer,2008,17(7):563-564.
12 .卢泰祥,韩非,李嘉欣.复发鼻咽癌临床研究进展[J].中国癌症杂志,2008,18(9):661-666.LU Taixiang,HAN Fei,LI Jiaxin.Advance in the clinical research On local recurrent nasopharyngeal carcinoma[J].China Oncology,2008,18(9):661-666.
13 .唐宁,金洁,邓云,等.人源性长寿保障基因2通过与V-ATPase作用抑制肝癌细胞的生长[J].生理学报,2010,62(3):196-202.TANG Ning,JIN Jie,DENG Yun,et al.L A SS2 interacts w ith V-ATPase and inhibits cell growth of hepatocellular carcinoma[J].Acta Physiologica Sinica,2010,62(3):196-202.
14 .You H,Jin J,Shu H,et al.Small interfering RNA targeting the subunit ATP6L of proton pump V-ATPase overcomes chemoresistance of breast cancer cells[J].Cancer Lett,2009,280(1):110-119.
15 .Xu XY,Pei F,You JF.TMSG-1 and its roles in tumor biology[J].Chin J Cancer,2010,29(7):697-702.
16 .谭宁,覃文新,万晓桢,等.LASS2基因抑制HCCLM3肝癌细胞的转移[J].肿瘤,2007,27(5):335-340.TAN Ning,QIN Wenxin,WAN Xiaozhen,et al.LASS2 gene inhibits the metastasis of human hepatocellular carcinoma HCCLM3 cells[J].Tumor,2007,27(5):335-340.
17 .Fan S,Niu Y,Tan N,et al.LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump[J].Oncogene,2013,32:1682-1690.
18 .Wang H,Yang D,Wang K,et al.Expression and potential role of chemokine receptor CXCR4 in human bladder carcinoma cell lines with different metastatic ability[J].Mol Med Rep,2011,4(3):525-528.
19 .徐晓艳,由江峰,裴斐,等.RNA沉默LASS2基因促进人前列腺癌细胞体外侵袭及其机制研究[J].北京大学学报(医学版),2011,43(6):814-819.XU Xiaoyan,YOU Jiangfeng,PEI Fei,et al.Silencing of tumor metastasis suppressor gene 1 promotes invasion of prostate cancer cell in vitro and its molecular mechanisms[J].Journal of Peking University.Health Sciences,2011,43(6):814-819.