LINE-1在肿瘤早期诊断和治疗中的研究与应用

doi:10.16288/j.yczz.21-062

遗传 ›› 2021, Vol. 43 ›› Issue (6): 571-579.doi: 10.16288/j.yczz.21-062

LINE-1在肿瘤早期诊断和治疗中的研究与应用

寇艳妮, 岑山(), 李晓宇()

中国医学科学院&北京协和医学院,医药生物技术研究所免疫生物学室,北京 100050

收稿日期:2021-02-10 修回日期:2021-05-07 出版日期:2021-06-20 发布日期:2021-05-28
通讯作者: 岑山,李晓宇 E-mail:shancen@imb.pumc.edu.cn;xiaoyulik@hotmail.com
作者简介:寇艳妮,在读硕士研究生,专业方向：LINE-1与肿瘤维持的内在机制研究。E-mail: yanni_1995@126.com
基金资助:
国家科技重大专项编号(2018ZX10301408-004);国家自然科学基金资助编号(31870164)

Research and application on LINE-1 in diagnosis and treatment of tumorigenesis

Yanni Kou, Shan Cen(), Xiaoyu Li()

Department of Immunology, Institute of Medicinal Biotechnology, Chinese academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Received:2021-02-10 Revised:2021-05-07 Online:2021-06-20 Published:2021-05-28
Contact: Cen Shan,Li Xiaoyu E-mail:shancen@imb.pumc.edu.cn;xiaoyulik@hotmail.com
Supported by:
Supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China No(2018ZX10301408-004);the National Natural Science Foundation of China No(31870164)

摘要/Abstract

摘要：

长散布元件-1 (long interspersed elements-1, LINE-1)约占人类基因组的17%,是人类基因组中唯一具有自主转座能力的转座子。LINE-1可通过逆转录转座过程插入到新的基因位点上,从而会导致基因组的不稳定。因而机体对LINE-1的复制和转座有着严格的限制,在正常体细胞中几乎检测不到LINE-1的表达。然而,在绝大多数的肿瘤组织或癌组织中LINE-1的表达却普遍存在,提示LINE-1的表达和转座与肿瘤的发生发展密切相关。LINE-1在肿瘤细胞中的差异表达可以作为肿瘤早期诊断的标志物,同时也可作为肿瘤治疗预后评价的重要指标。与此同时,LINE-1作为肿瘤治疗潜在靶点的可行性也在评估和验证中。本文介绍了在临床方面LINE-1作为肿瘤诊断、预后方面的应用,以及作为肿瘤治疗潜在靶点的研究进展,以期为临床上肿瘤的诊断和治疗提供一些参考。

关键词: 长散布元件-1, 肿瘤, 诊断, 治疗, 预后

Abstract:

Long interspersed element-1 (LINE-1), which is the only autonomous retrotransposon in human genome, makes up about 17% of the human genome. For LINE-1 retrotransposition may result in genome instability, it was strictly restricted by organisms, and its expression was therefore barely detected in normal somatic cells. However, the expression of LINE-1 is a common phenomenon in most tumor or cancer tissues, suggesting a close relationship between LINE-1 expression and cancer development. Differentially expressed LINE-1 in cancer tissues can be used as a biomarker for tumor diagnosis and an important indicator of prognosis after cancer therapeutics. Meanwhile, the feasibility of LINE-1 as a potential drug target for tumor treatment has also been evaluating and verifying in clinicals. In this review, we introduce the application of LINE-1 as a biomarker in tumor diagnosis and prognostic, as well as the research progress in LINE-1 as potential drug target for tumor treatment, in order to provide some references for clinical application in cancer treatment.

Key words: long interspersed element-1, tumor, diagnosis, treatment, prognosis

寇艳妮, 岑山, 李晓宇. LINE-1在肿瘤早期诊断和治疗中的研究与应用[J]. 遗传, 2021, 43(6): 571-579.

Yanni Kou, Shan Cen, Xiaoyu Li. Research and application on LINE-1 in diagnosis and treatment of tumorigenesis[J]. Hereditas(Beijing), 2021, 43(6): 571-579.

图/表 2

参考文献 63

[1]	Burns KH. Transposable elements in cancer. Nat Rev Cancer, 2017,17(7):415-424.
[2]	Goodier JL, Kazazian HH. Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell, 2008,135(1):23-35.
[3]	De Cecco M, Ito T, Petrashen AP, Elias AE, Skvir NJ, Criscione SW, Caligiana A, Brocculi G, Adney EM, Boeke JD, Le O, Beauséjour C, Ambati J, Ambati K, Simon M, Seluanov A, Gorbunova V, Slagboom PE, Helfand SL, Neretti N, Sedivy JM. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature, 2019,566(7742):73-78.
[4]	Hancks DC, Kazazian HH. Roles for retrotransposon insertions in human disease. Mob DNA, 2016,7:9.
[5]	Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011,144(5):646-674.
[6]	Liu Q, Wang JH, Li XY, Cen S. The connection between LINE-1 retrotransposition and human tumorigenesis. Hereditas(Beijing), 2016,38(2):93-102.
	刘茜, 王瑾晖, 李晓宇, 岑山. 逆转录转座子LINE-1与肿瘤的发生和发展. 遗传, 2016,38(2):93-102.
[7]	Zhang X, Zhang R, Yu JP. New understanding of the relevant role of LINE-1 retrotransposition in human disease and immune modulation. Front Cell Dev Biol, 2020,8:657.
[8]	Bodak M, Yu J, Ciaudo C. Regulation of LINE-1 in mammals. Biomol Concepts, 2014,5(5):409-428.
[9]	Deniz Ö, Frost JM, Branco MR. Regulation of transposable elements by DNA modifications. Nat Rev Genet, 2019,20(7):417-431.
[10]	Elbarbary RA, Lucas BA, Maquat LE. Retrotransposons as regulators of gene expression. Science, 2016, 351(6274): aac7247.
[11]	Terasaki N, Goodier JL, Cheung LE, Wang YJ, Kajikawa M, Kazazian HH, Okada N. In vitro screening for compounds that enhance human L1 mobilization. PLoS One, 2013,8(9):e74629.
[12]	Grundy EE, Diab N, Chiappinelli KB. Transposable element regulation and expression in cancer. FEBS J, 2021, doi: 10.1111/febs.15722.
[13]	Dolci M, Favero C, Toumi W, Favi E, Tarantini L, Signorini L, Basile G, Bollati V, D'Alessandro S, Bagnoli P, Ferrante P, Delbue S. Human endogenous retroviruses long terminal repeat methylation, transcription, and protein expression in human colon cancer. Front Oncol, 2020,10:569015.
[14]	Ko EJ, Oh YL, Kim HY, Eo WK, Kim H, Ock MS, Kim HS, Kim KH, Cha HJ. Correlation of long interspersed element-1 open reading frame 1 and c-Met proto-oncogene protein expression in ovarian cancer. Genes Genomics, 2019,41(11):1293-1299.
[15]	Daskalos A, Nikolaidis G, Xinarianos G, Savvari P, Cassidy A, Zakopoulou R, Kotsinas A, Gorgoulis V, Field JK, Liloglou T. Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer. Int J Cancer, 2009,124(1):81-87.
[16]	Harada K, Baba Y, Ishimoto T, Chikamoto A, Kosumi K, Hayashi H, Nitta H, Hashimoto D, Beppu T, Baba H. LINE-1 methylation level and patient prognosis in a database of 208 hepatocellular carcinomas. Ann Surg Oncol, 2015,22(4):1280-1287.
[17]	Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, Iwatsuki M, Sakamaki K, Ohashi Y, Baba H. LINE-1 hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Ann Surg, 2013,257(3):449-455.
[18]	van Hoesel AQ, van de Velde CJH, Kuppen PJK, Liefers GJ, Putter H, Sato Y, Elashoff DA, Turner RR, Shamonki JM, de Kruijf EM, van Nes JGH, Giuliano AE, Hoon DSB. Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study. Breast Cancer Res Treat, 2012,134(3):1103-1114.
[19]	Weber B, Kimhi S, Howard G, Eden A, Lyko F. Demethylation of a LINE-1 antisense promoter in the cMet locus impairs Met signalling through induction of illegitimate transcription. Oncogene, 2010,29(43):5775-5784.
[20]	Wolff EM, Byun HM, Han HF, Sharma S, Nichols PW, Siegmund KD, Yang AS, Jones PA, Liang GN. Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer. PLoS Genet, 2010,6(4):e1000917.
[21]	Roman-Gomez J, Jimenez-Velasco A, Agirre X, Cervantes F, Sanchez J, Garate L, Barrios M, Castillejo JA, Navarro G, Colomer D, Prosper F, Heiniger A, Torres A. Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia. Oncogene, 2005,24(48):7213-7223.
[22]	Lin L, Wang ZW, Prescott MS, van Dekken H, Thomas DG, Giordano TJ, Chang AC, Orringer MB, Gruber SB, Moran JV, Glover TW, Beer DG. Multiple forms of genetic instability within a 2-Mb chromosomal segment of 3q26.3-q27 are associated with development of esophageal adenocarcinoma. Genes Chromosomes Cancer, 2006,45(4):319-331.
[23]	Miret N, Zappia CD, Altamirano G, Pontillo C, Zárate L, Gómez A, Lasagna M, Cocca C, Kass L, Monczor F, Randi A. AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG. Biochem Pharmacol, 2020,175:113904.
[24]	Tharp ME, Malki S, Bortvin A. Maximizing the ovarian reserve in mice by evading LINE-1 genotoxicity. Nat Commun, 2020,11(1):330.
[25]	Rodić N, Sharma R, Zampella J, Dai LX, Taylor MS, Hruban RH, Iacobuzio-Donahue CA, Maitra A, Torbenson MS, Goggins M, Shih IM, Duffield AS, Montgomery EA, Gabrielson E, Netto GJ, Lotan TL, De Marzo AM, Westra W, Binder ZA, Orr BA, Gallia GL, Eberhart CG, Boeke JD, Harris CR, Burns KH. Long interspersed element-1 protein expression is a hallmark of many human cancers. Am J Pathol, 2014,184(5):1280-1286.
[26]	Rodić N, Steranka JP, Makohon-Moore A, Moyer A, Shen PL, Sharma R, Kohutek ZA, Huang CR, Ahn D, Mita P, Taylor MS, Barker NJ, Hruban RH, Iacobuzio-Donahue CA, Boeke JD, Burns KH. Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma. Nat Med, 2015,21(9):1060-1064.
[27]	Doucet-O'Hare TT, Rodić N, Sharma R, Darbari I, Abril G, Choi JA, Young Ahn J, Cheng YL, Anders RA, Burns KH, Meltzer SJ, Kazazian HH. LINE-1 expression and retrotransposition in Barrett's esophagus and esophageal carcinoma. Proc Natl Acad Sci USA, 2015,112(35):E4894-E4900.
[28]	Papasotiriou I, Pantopikou K, Apostolou P. L1 retrotransposon expression in circulating tumor cells. PLoS One, 2017,12(2):e0171466.
[29]	Tristán-Ramos P, Rubio-Roldan A, Peris G, Sánchez L, Amador-Cubero S, Viollet S, Cristofari G, Heras SR. The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition. Nat Commun, 2020,11(1):5712.
[30]	De Luca C, Guadagni F, Sinibaldi-Vallebona P, Sentinelli S, Gallucci M, Hoffmann A, Schumann GG, Spadafora C, Sciamanna I. Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation. Oncotarget, 2016,7(4):4048-4061.
[31]	Briggs EM, Spadafora C, Logan SK. A re-evaluation of LINE-1 ORF2 expression in LNCaP prostate cancer cells. Mob DNA, 2019,10:51.
[32]	Chiou PT, Ohms S, Board PG, Dahlstrom JE, Rangasamy D, Casarotto MG. Efavirenz as a potential drug for the treatment of triple-negative breast cancers. Clin Transl Oncol, 2021,23(2):353-363.
[33]	Shademan M, Zare K, Zahedi M, Mosannen Mozaffari H, Bagheri Hosseini H, Ghaffarzadegan K, Goshayeshi L, Dehghani H. Promoter methylation, transcription, and retrotransposition of LINE-1 in colorectal adenomas and adenocarcinomas. Cancer Cell Int, 2020,20:426.
[34]	Kerachian MA, Kerachian M. Long interspersed nucleotide element-1 (LINE-1) methylation in colorectal cancer. Clin Chim Acta, 2019,488:209-214.
[35]	Wang XY, Zhang Y, Yang N, Cheng H, Sun YJ. DNMT3a mediates paclitaxel-induced abnormal expression of LINE-1 by increasing the intragenic methylation. Hereditas (Beijing), 2020,42(1):100-111.
	王昕源, 张雨, 杨楠, 程禾, 孙玉洁. DNMT3a通过提升基因内部甲基化介导紫杉醇诱导的LINE-1异常表达. 遗传, 2020,42(1):100-111.
[36]	Chalitchagorn K, Shuangshoti S, Hourpai N, Kongruttanachok N, Tangkijvanich P, Thong-ngam D, Voravud N, Sriuranpong V, Mutirangura A. Distinctive pattern of LINE-1 methylation level in normal tissues and the association with carcinogenesis. Oncogene, 2004,23(54):8841-8846.
[37]	Belancio VP, Roy-Engel AM, Pochampally RR, Deininger P. Somatic expression of LINE-1 elements in human tissues. Nucleic Acids Res, 2010,38(12):3909-3922.
[38]	Pattamadilok J, Huapai N, Rattanatanyong P, Vasurattana A, Triratanachat S, Tresukosol D, Mutirangura A. LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer. Int J Gynecol Cancer, 2008,18(4):711-717.
[39]	Barchitta M, Quattrocchi A, Maugeri A, Vinciguerra M, Agodi A. LINE-1 hypomethylation in blood and tissue samples as an epigenetic marker for cancer risk: a systematic review and meta-analysis. PLoS One, 2014,9(10):e109478.
[40]	Rodić N, Sharma R, Sharma R, Zampella J, Dai LX, Taylor MS, Hruban RH, Iacobuzio-Donahue CA, Maitra A, Torbenson MS, Goggins M, Shih IM, Duffield AS, Montgomery EA, Gabrielson E, Netto GJ, Lotan TL, De Marzo AM, Westra W, Binder ZA, Orr BA, Gallia GL, Eberhart CG, Boeke JD, Harris CR, Burns KH. Long interspersed element-1 protein expression is a hallmark of many human cancers. Am J Pathol, 2014,184(5):1280-1286.
[41]	Lavasanifar A, Sharp CN, Korte EA, Yin T, Hosseinnejad K, Jortani SA. Long interspersed nuclear element-1 mobilization as a target in cancer diagnostics, prognostics and therapeutics. Clin Chim Acta, 2019,493:52-62.
[42]	Hosseinnejad K, Yin T, Gaskins JT, Bailen JL, Jortani SA. Discovery of the long interspersed nuclear element-1 activation product [open reading frame-1 (ORF1) protein] in human blood. Clin Chim Acta, 2018,487:228-232.
[43]	Gasior SL, Wakeman TP, Xu B, Deininger PL. The human LINE-1 retrotransposon creates DNA double-strand breaks. J Mol Biol, 2006,357(5):1383-1393.
[44]	Alisch RS, Garcia-Perez JL, Muotri AR, Gage FH, Moran JV. Unconventional translation of mammalian LINE-1 retrotransposons. Genes Dev, 2006,20(2):210-224.
[45]	Gualtieri A, Andreola F, Sciamanna I, Sinibaldi-Vallebona P, Serafino A, Spadafora C. Increased expression and copy number amplification of LINE-1 and SINE B1 retrotransposable elements in murine mammary carcinoma progression. Oncotarget, 2013,4(11):1882-1893.
[46]	Sciamanna I, De Luca C, Spadafora C. The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression, and therapy of cancer. Front Chem, 2016,4:6.
[47]	Sciamanna I, Landriscina M, Pittoggi C, Quirino M, Mearelli C, Beraldi R, Mattei E, Serafino A, Cassano A, Sinibaldi-Vallebona P, Garaci E, Barone C, Spadafora C. Inhibition of endogenous reverse transcriptase antagonizes human tumor growth. Oncogene, 2005,24(24):3923-3931.
[48]	Oricchio E, Sciamanna I, Beraldi R, Tolstonog GV, Schumann GG, Spadafora C. Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression. Oncogene, 2007,26(29):4226-4233.
[49]	Patnala R, Lee SH, Dahlstrom JE, Ohms S, Chen L, Dheen ST, Rangasamy D. Inhibition of LINE-1 retrotransposon- encoded reverse transcriptase modulates the expression of cell differentiation genes in breast cancer cells. Breast Cancer Res Treat, 2014,143(2):239-253.
[50]	Zhu YF, Feng F, Yu JY, Song B, Hu MM, Gao XD, Wang Y, Zhang Q. L1-ORF1p, a Smad4 interaction protein, promotes proliferation of HepG2 cells and tumorigenesis in mice. DNA Cell Biol, 2013,32(9):531-540.
[51]	Hur K, Cejas P, Feliu J, Moreno-Rubio J, Burgos E, Boland CR, Goel A. Hypomethylation of long interspersed nuclear element-1 (LINE-1) leads to activation of proto- oncogenes in human colorectal cancer metastasis. Gut, 2014,63(4):635-646.
[52]	Kuo KW, Sheu HM, Huang YS, Leung WC. Expression of transposon LINE-1 is relatively human-specific and function of the transcripts may be proliferation-essential. Biochem Biophys Res Commun, 1998,253(3):566-570.
[53]	Banuelos-Sanchez G, Sanchez L, Benitez-Guijarro M, Sanchez-Carnerero V, Salvador-Palomeque C, Tristan- Ramos P, Benkaddour-Boumzaouad M, Morell S, Garcia- Puche JL, Heras SR, Franco-Montalban F, Tamayo JA, Garcia-Perez JL. Synthesis and characterization of specific reverse transcriptase inhibitors for mammalian LINE-1 retrotransposons. Cell Chem Biol, 2019, 26(8): 1095-1109.e14.
[54]	Bellisai C, Sciamanna I, Rovella P, Giovannini D, Baranzini M, Pugliese GM, Zeya Ansari MS, Milite C, Sinibaldi-Vallebona P, Cirilli R, Sbardella G, Pichierri P, Trisciuoglio D, Lavia P, Serafino A, Spadafora C. Reverse transcriptase inhibitors promote the remodelling of nuclear architecture and induce autophagy in prostate cancer cells. Cancer lett, 2020,478:133-145.
[55]	Houédé N, Pulido M, Mourey L, Joly F, Ferrero JM, Bellera C, Priou F, Lalet C, Laroche-Clary A, Raffin MC, Ichas F, Puech A, Piazza PV. A phase II trial evaluating the efficacy and safety of efavirenz in metastatic castration- resistant prostate cancer. Oncologist, 2014,19(12):1227-1228.
[56]	Carlini F, Ridolfi B, Molinari A, Parisi C, Bozzuto G, Toccacieli L, Formisano G, De Orsi D, Paradisi S, Grober OMV, Ravo M, Weisz A, Arcieri R, Vella S, Gaudi S. The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines. PloS One, 2010,5(12):e14221.
[57]	Aschacher T, Sampl S, Käser L, Bernhard D, Spittler A, Holzmann K, Bergmann M. The combined use of known antiviral reverse transcriptase inhibitors AZT and DDI induce anticancer effects at low concentrations. Neoplasia, 2012,14(1):44-53.
[58]	Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Chan AT, Schernhammer ES, Giovannucci EL, Fuchs CS. A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. J Natl Cancer Inst, 2008,100(23):1734-1738.
[59]	Zhu J, Ling Y, Xu Y, Lu MZ, Liu YP, Zhang CS. Elevated expression of MDR1 associated with Line-1 hypomethylation in esophageal squamous cell carcinoma. Int J Clin Exp Pathol, 2015,8(11):14392-14400.
[60]	Huang Y, Wei L, Sun AM, Zhao RC, Zhang J, Yang HT, Li B, Sun CJ, Ding XQ, Gao B, Zhong YQ, Qin Y. The evaluation value of methylation status of CpG island of SFRP1 and LINE1 gene promoter area in the prognosis of hepatocellular carcinom. J Sichuan Univ(Med Sci Ed), 2016,47(6):883-888.
	黄元, 魏玲, 孙爱民, 赵荣策, 张静, 杨含腾, 李波, 孙成均, 丁雪琴, 高波, 钟艳琴, 覃扬. SFRP1、LINE1基因启动子区CpG岛甲基化状态在肝细胞癌预后评估的价值. 四川大学学报(医学版). 2016,47(6):883-888.
[61]	Wang CH, Meng FK, Fei SY, Chen M, Zheng LJ. The clinical significance of retrotransposon expression in glioma. Chin J Lab Diag, 2020,24(8):1308-1310.
	王春辉, 孟繁凯, 费邵阳, 陈莫, 郑林杰. 逆转座子LINE-1在脑胶质瘤中异常活化的临床意义. 中国实验诊断学, 2020,24(8):1308-1310.
[62]	Harris CR, Normart R, Yang QF, Stevenson E, Haffty BG, Ganesan S, Cordon-Cardo C, Levine AJ, Tang LH. Association of nuclear localization of a long interspersed nuclear element-1 protein in breast tumors with poor prognostic outcomes. Genes Cancer, 2010,1(2):115-124.
[63]	Chen L, Dahlstrom JE, Chandra A, Board P, Rangasamy D. Prognostic value of LINE-1 retrotransposon expression and its subcellular localization in breast cancer. Breast Cancer Res Treat, 2012,136(1):129-142.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

LINE-1的异常表征	癌症实例	参考文献
LINE-1启动子低甲基化	结肠癌、卵巢癌、非小细胞肺癌、肝细胞癌、食管鳞状细胞癌、乳腺癌、急性髓性白血病、膀胱癌	[13~20]
LINE-1 RNA 表达	慢性粒细胞白血病、食管腺癌、乳腺癌、卵巢癌	[21~24]
ORF1p表达	乳腺癌、卵巢癌、胰腺癌、食道癌、结肠癌、肺癌、前列腺癌	[23~29]
ORF2p表达	结肠癌、前列腺癌、肺腺癌、乳腺浸润性导管癌	[29~32]

LINE-1在肿瘤早期诊断和治疗中的研究与应用

Research and application on LINE-1 in diagnosis and treatment of tumorigenesis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 2

参考文献 63

相关文章 15

编辑推荐

Metrics

[1]	孙清玙, 周阳, 杜丽娟, 张梦珂, 王家乐, 任媛媛, 刘芳. 巨噬细胞相关基因与非小细胞肺癌预后和肿瘤微环境的分析[J]. 遗传, 2023, 45(8): 684-699.
[2]	严程浩, 白韦钰, 张智猛, 沈俊岭, 王友军, 孙建伟. STIM1在肿瘤发生及转移中的研究进展[J]. 遗传, 2023, 45(5): 395-408.
[3]	马春辉, 胡海旭, 张丽娟, 刘毅, 刘天懿. 用于循环肿瘤细胞定量分析的CK19数字PCR检测方法的建立及性能验证[J]. 遗传, 2023, 45(3): 250-260.
[4]	常栋, 刘享享, 刘睿, 孙建伟. FSCN1在乳腺癌发生发展中的作用及其调控机制[J]. 遗传, 2023, 45(2): 115-127.
[5]	田智琛, 尹晓娟. 诱导多能干细胞在儿童疾病的应用研究进展[J]. 遗传, 2023, 45(1): 42-51.
[6]	曾焙枰, 许红恩, 毛璐, 汤文学. 遗传性耳聋分子诊断及梯级检测策略应用[J]. 遗传, 2023, 45(1): 29-41.
[7]	郝庆刚, 孙凤桂, 严程浩, 孙建伟. MT1-MMP在肿瘤转移中的研究进展[J]. 遗传, 2022, 44(9): 745-755.
[8]	赵岩, 王晨鑫, 杨天明, 李春爽, 张丽宏, 杜冬妮, 王若曦, 王静, 魏民, 巴雪青. DNA氧化损伤8-羟鸟嘌呤与肿瘤的发生发展[J]. 遗传, 2022, 44(6): 466-477.
[9]	舒甜, 胡豪畅, 沈才杰, 林少沂, 陈晓敏. 肥厚型心肌病基因型-表型关联研究进展[J]. 遗传, 2022, 44(3): 198-207.
[10]	程敏, 张静, 曹鹏博, 周钢桥. 缺氧相关长链非编码RNA作为肝癌预后预测标志物的潜在价值[J]. 遗传, 2022, 44(2): 153-167.
[11]	沈敏, 顾愹, 应长江, 张梅, 杨涛, 陈阳. 一例胰腺纤维钙化性糖尿病的诊疗和基因检测分析[J]. 遗传, 2022, 44(11): 1079-1086.
[12]	梁佳琦, 刘畅, 张雯翔, 陈思禹. 肝脏分泌因子与代谢性疾病[J]. 遗传, 2022, 44(10): 853-866.
[13]	雷常贵, 贾学渊, 孙文靖. 基于癌症基因组图谱计划多组学数据构建胶质母细胞瘤六基因预后模型[J]. 遗传, 2021, 43(7): 665-679.
[14]	王卓, 申笑涵, 施奇惠. 单细胞基因组测序技术新进展及其在生物医学中的应用[J]. 遗传, 2021, 43(2): 108-117.
[15]	刘倩, 李春燕. 增强子的鉴定及其在肿瘤研究中的应用[J]. 遗传, 2020, 42(9): 817-831.