[논문]GCC2 as a New Early Diagnostic Biomarker for Non-Small Cell Lung Cancer

Jeong, Hyesun; Choi, Byeong Hyeon; Park, JinA; Jung, Jik-Han; Shin, Hyunku; Kang, Ka-Won; Quan, Yu Hua; Yu, Jewon; Park, Ji-Ho; Park, Yong; Choi, Yeonho; Kim, Hyun Koo; Hong, Sunghoi

doi:10.3390/cancers13215482

[해외논문] GCC2 as a New Early Diagnostic Biomarker for Non-Small Cell Lung Cancer 원문보기

Cancers, v.13 no.21, 2021년, pp.5482 -

Jeong, Hyesun (School of Biosystems and Biomedical Sciences, Korea University, Seoul 02841, Korea) , Choi, Byeong Hyeon (lullaby0810@gmail.com (H.J.)) , Park, JinA (2020020815@korea.ac.kr (J.P.)) , Jung, Jik-Han (Korea Artificial Organ Center, Korea University, Seoul 02841, Korea) , Shin, Hyunku (baby2music@gmail.com) , Kang, Ka-Won (School of Biosystems and Biomedical Sciences, Korea University, Seoul 02841, Korea) , Quan, Yu Hua (lullaby0810@gmail.com (H.J.)) , Yu, Jewon (2020020815@korea.ac.kr (J.P.)) , Park, Ji-Ho (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea) , Park, Yong (jjhan@kaist.ac.kr (J.-H.J.)) , Choi, Yeonho (jihopark@kaist.ac.kr (J.-H.P.)) , Kim, Hyun Koo (Department of Bio-Convergence Engineering, Korea University, Seoul 02841, Korea) , Hong, Sunghoi (ramgee91@gmail.com)

Abstract ▼ AI-Helper

Simple SummaryLung cancer, including non-small cell lung cancer, is the leading cause of cancer-related death worldwide. A better prognosis is associated with early diagnosis of lung cancer patients. Although annual screening guidelines for lung cancer are recommended, using various tools such as chest X-ray, low-dose computed tomography, and positron emission tomography, these screening procedures are expensive and difficult to repeat. They are also invasive and have a high risk of radiation exposure. Therefore, a low-risk, convenient diagnostic method using liquid biopsy and biomarkers is required for the early diagnosis of lung cancer. The newly proposed biomarker GCC2 was identified through proteomic analysis of exosomes secreted from lung cancer cell lines. GCC2 expression levels in peripheral blood of the patients showed high specificity and sensitivity in early lung cancer, demonstrating that our novel exosomal biomarker GCC2 can greatly contribute to improving the diagnosis of lung cancer patients, even though it has been tested in only a few pilot studies.AbstractNo specific markers have been identified to detect non-small cell lung cancer (NSCLC) cell-derived exosomes circulating in the blood. Here, we report a new biomarker that distinguishes between cancer and non-cancer cell-derived exosomes. Exosomes isolated from patient plasmas at various pathological stages of NSCLC, NSCLC cell lines, and human pulmonary alveolar epithelial cells isolated using size exclusion chromatography were characterized. The GRIP and coiled-coil domain-containing 2 (GCC2) protein, involved in endosome-to-Golgi transport, was identified by proteomics analysis of NSCLC cell line-derived exosomes. GCC2 protein levels in the exosomes derived from early-stage NSCLC patients were higher than those from healthy controls. Receiver operating characteristic curve analysis revealed the diagnostic sensitivity and specificity of exosomal GCC2 to be 90% and 75%, respectively. A high area under the curve, 0.844, confirmed that GCC2 levels could effectively distinguish between the exosomes. These results demonstrate GCC2 as a promising early diagnostic biomarker for NSCLC.

Keyword

참고문헌 (44)

1. Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2019 CA-Cancer J. Clin. 2019 69 7 34 10.3322/caac.21551 30620402

상세보기
2. Spira A. Ettinger D.S. Multidisciplinary management of lung cancer N. Engl. J. Med. 2004 350 379 392 10.1056/NEJMra035536 14736930

상세보기
3. Zappa C. Mousa S.A. Non-small cell lung cancer: Current treatment and future advances Transl. Lung Cancer Res. 2016 5 288 300 10.21037/tlcr.2016.06.07 27413711
4. Goebel C. Louden C.L. McKenna R. Jr. Onugha O. Wachtel A. Long T. Diagnosis of Non-small Cell Lung Cancer for Early Stage Asymptomatic Patients Cancer Genom. Proteom. 2019 16 229 244 10.21873/cgp.20128 31243104

상세보기
5. Fountain S.W. Armstrong P. Congleton J. Jagoe T. McAuley D.F. MacMahon J. Muers M.F. Page R.D. Plant P.K. Roland M. Guidelines on the selection of patients with lung cancer for surgery Thorax 2001 56 89 108 11209097
6. Raman V. Yang C.F.J. Deng J.Z. D’Amico T.A. Surgical treatment for early stage non-small cell lung cancer J. Thorac. Dis. 2018 10 S898 S904 10.21037/jtd.2018.01.172 29780636

상세보기
7. Rosen J.E. Keshava H.B. Yao X.P. Kim A.W. Detterbeck F.C. Boffa D.J. The Natural History of Operable Non-Small Cell Lung Cancer in the National Cancer Database Ann. Thorac. Surg. 2016 101 1850 1855 10.1016/j.athoracsur.2016.01.077 27041452

상세보기
8. Reck M. Rabe K.F. Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer N. Engl. J. Med. 2017 377 849 861 10.1056/NEJMra1703413 28854088

상세보기
9. Liang W.H. Zhao Y. Huang W.Z. Liang H.R. Zeng H.K. He J.X. Liquid biopsy for early stage lung cancer J. Thorac. Dis. 2018 10 S876 S881 10.21037/jtd.2018.04.26 29780634

상세보기
10. Bardelli A. Pantel K. Liquid Biopsies, What We Do Not Know (Yet) Cancer Cell 2017 31 172 179 10.1016/j.ccell.2017.01.002 28196593

상세보기
11. Palmirotta R. Lovero D. Cafforio P. Felici C. Mannavola F. Pelle E. Quaresmini D. Tucci M. Silvestris F. Liquid biopsy of cancer: A multimodal diagnostic tool in clinical oncology Ther. Adv. Med. Oncol. 2018 10 1758835918794630 10.1177/1758835918794630 30181785

상세보기
12. Zhang W. Xia W. Lv Z. Ni C. Xin Y. Yang L. Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes? Cell. Physiol. Biochem. 2017 41 755 768 10.1159/000458736 28214887

상세보기
13. Kalluri R. LeBleu V.S. The biology, function, and biomedical applications of exosomes Science 2020 367 6478 10.1126/science.aau6977 32029601

상세보기
14. Pan B.T. Teng K. Wu C. Adam M. Johnstone R.M. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes J. Cell Biol. 1985 101 942 948 10.1083/jcb.101.3.942 2993317

상세보기
15. Trajkovic K. Ceramide triggers budding of exosome vesicles into multivesicular endosomes Science 2008 319 1244 1247 18309083

상세보기
16. Ostrowski M. Carmo N.B. Krumeich S. Fanget I. Raposo G. Savina A. Moita C.F. Schauer K. Hume A.N. Freitas R.P. Rab27a and Rab27b control different steps of the exosome secretion pathway Nat. Cell Biol. 2010 12 19 30 10.1038/ncb2000 19966785

상세보기
17. Mulcahy L.A. Pink R.C. Carter D.R. Routes and mechanisms of extracellular vesicle uptake J. Extracell. Vesicles 2014 3 10.3402/jev.v3.24641

상세보기
18. Zhao H. Yang L. Baddour J. Achreja A. Bernard V. Moss T. Marini J.C. Tudawe T. Seviour E.G. San Lucas F.A. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism Elife 2016 5 e10250 10.7554/eLife.10250 26920219

상세보기
19. Taylor D.D. Gercel-Taylor C. Exosomes/microvesicles: Mediators of cancer-associated immunosuppressive microenvironments Semin. Immunopathol. 2011 33 441 454 10.1007/s00281-010-0234-8 21688197

상세보기
20. Li Q. Shao Y.F. Zhang X.J. Zheng T. Miao M. Qin L.J. Wang B.J. Ye G.L. Xiao B.X. Guo J.M. Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer Tumor Biol. 2015 36 2007 2012 10.1007/s13277-014-2807-y

상세보기
21. Madhavan B. Yue S.J. Galli U. Rana S. Gross W. Muller M. Giese N.A. Kalthoff H. Becker T. Buchler M.W. Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity Int. J. Cancer 2015 136 2616 2627 10.1002/ijc.29324 25388097

상세보기
22. Thakur B.K. Zhang H. Becker A. Matei I. Huang Y. Costa-Silva B. Zheng Y. Hoshino A. Brazier H. Xiang J. Double-stranded DNA in exosomes: A novel biomarker in cancer detection Cell Res. 2014 24 766 769 10.1038/cr.2014.44 24710597

상세보기
23. Thind A. Wilson C. Exosomal miRNAs as cancer biomarkers and therapeutic targets J. Extracell. Vesicles 2016 5 31292 10.3402/jev.v5.31292 27440105

상세보기
24. Luke M.R. Kjer-Nielsen L. Brown D.L. Stow J.L. Gleeson P.A. GRIP domain-mediated targeting of two new coiled-coil proteins, GCC88 and GCC185, to subcompartments of the trans-Golgi network J. Biol. Chem. 2003 278 4216 4226 10.1074/jbc.M210387200 12446665

상세보기
25. Reddy J.V. Burguete A.S. Sridevi K. Ganley I.G. Nottingham R.M. Pfeffer S.R. A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling Mol. Biol. Cell 2006 17 4353 4363 10.1091/mbc.e06-02-0153 16885419

상세보기
26. Derby M.C. Lieu Z.Z. Brown D. Stow J.L. Goud B. Gleeson P.A. The trans-Golgi network golgin, GCC185, is required for endosome-to-Golgi transport and maintenance of Golgi structure Traffic 2007 8 758 773 10.1111/j.1600-0854.2007.00563.x 17488291

상세보기
27. Jiang J.H. Wu X. Tong X.L. Wei W.Z. Chen A. Wang X.N. Shao Y.W. Huang J.A. GCC2-ALK as a targetable fusion in lung adenocarcinoma and its enduring clinical responses to ALK inhibitors Lung Cancer 2018 115 5 11 10.1016/j.lungcan.2017.10.011 29290262

상세보기
28. Zheng H.M. Zhan Y.T. Liu S.L. Lu J.M. Luo J.D. Feng J. Fan S.Q. The roles of tumor-derived exosomes in non-small cell lung cancer and their clinical implications J. Exp. Clin. Cancer Res. 2018 37 226 10.1186/s13046-018-0901-5 30217217

상세보기
29. Coumans F.A.W. Brisson A.R. Buzas E.I. Dignat-George F. Drees E.E.E. El-Andaloussi S. Emanueli C. Gasecka A. Hendrix A. Hill A.F. Methodological Guidelines to Study Extracellular Vesicles Circ. Res. 2017 120 1632 1648 10.1161/CIRCRESAHA.117.309417 28495994

상세보기
30. Muller L. Hong C.S. Stolz D.B. Watkins S.C. Whiteside T.L. Isolation of biologically-active exosomes from human plasma J. Immunol. Methods 2014 411 55 65 10.1016/j.jim.2014.06.007 24952243

상세보기
31. Park J. Hwang M. Choi B. Jeong H. Jung J.H. Kim H.K. Hong S. Park J.H. Choi Y. Exosome Classification by Pattern Analysis of Surface-Enhanced Raman Spectroscopy Data for Lung Cancer Diagnosis Anal. Chem. 2017 89 6695 6701 10.1021/acs.analchem.7b00911 28541032

상세보기
32. Shin H. Jeong H. Park J. Hong S. Choi Y. Correlation between Cancerous Exosomes and Protein Markers Based on Surface-Enhanced Raman Spectroscopy (SERS) and Principal Component Analysis (PCA) Acs Sens. 2018 3 2637 2643 10.1021/acssensors.8b01047 30381940

상세보기
33. Shin H. Oh S. Hong S. Kang M. Kang D. Ji Y.G. Choi B.H. Kang K.W. Jeong H. Park Y. Early-Stage Lung Cancer Diagnosis by Deep Learning-Based Spectroscopic Analysis of Circulating Exosomes Acs Nano 2020 14 5435 5444 10.1021/acsnano.9b09119 32286793

상세보기
34. Kang K.W. Jung J.H. Hur W. Park J. Shin H. Choi B. Jeong H. Kim D.S. Yu E.S. Lee S.R. The Potential of Exosomes Derived from Chronic Myelogenous Leukaemia Cells as a Biomarker Anticancer Res. 2018 38 3935 3942 10.21873/anticanres.12679 29970515

상세보기
35. Brown F.C. Schindelhaim C.H. Pfeffer S.R. GCC185 plays independent roles in Golgi structure maintenance and AP-1-mediated vesicle tethering J. Cell Biol. 2011 194 779 787 10.1083/jcb.201104019 21875948

상세보기
36. Henschke C.I. Survival of patients with clinical stage I lung cancer diagnosed by computed tomography screening for lung cancer Clin. Cancer Res. 2007 13 4949 4950 10.1158/1078-0432.CCR-07-0317 17785541

상세보기
37. Scheff R.J. Schneider B.J. Non-small-cell lung cancer: Treatment of late stage disease: Chemotherapeutics and new frontiers Semin. Interv. Radiol. 2013 30 191 198 10.1055/s-0033-1342961 24436536

상세보기
38. Sandfeld-Paulsen B. Aggerholm-Pedersen N. Boek R. Jakobsen K.R. Melolgaard P. Folkersen B.H. Rasmussen T.R. Varming K. Jorgensen M.M. Sorensen B.S. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer Mol. Oncol. 2016 10 1595 1602 10.1016/j.molonc.2016.10.003 27856179

상세보기
39. Wang N. Song X.G. Liu L.S. Niu L.M. Wang X.W. Song X.R. Xie L. Circulating exosomes contain protein biomarkers of metastatic non-small-cell lung cancer Cancer Sci. 2018 109 1701 1709 10.1111/cas.13581 29573061

상세보기
40. Zhou B.T. Xu K.L. Zheng X. Chen T. Wang J. Song Y.M. Shao Y.K. Zheng S. Application of exosomes as liquid biopsy in clinical diagnosis Signal. Transduct. Target. Ther. 2020 5 144 10.1038/s41392-020-00258-9 32747657

상세보기
41. Lobb R.J. Becker M. Wen S.W. Wong C.S. Wiegmans A.P. Leimgruber A. Moller A. Optimized exosome isolation protocol for cell culture supernatant and human plasma J. Extracell. Vesicles 2015 4 27031 10.3402/jev.v4.27031 26194179

상세보기
42. Lin Y.C. Chiang T.C. Liu Y.T. Tsai Y.T. Jang L.T. Lee F.J.S. ARL4A acts with GCC185 to modulate Golgi complex organization J. Cell Sci. 2011 124 4014 4026 10.1242/jcs.086892 22159419

상세보기
43. Uhlen M. Fagerberg L. Hallstrom B.M. Lindskog C. Oksvold P. Mardinoglu A. Sivertsson A. Kampf C. Sjostedt E. Asplund A. Tissue-based map of the human proteome Science 2015 347 1260419 10.1126/science.1260419 25613900

상세보기
44. Wu Y. Wang Y. Wei M. Han X. Xu T. Cui M. Advances in the study of exosomal lncRNAs in tumors and the selection of research methods Biomed. Pharmacother. 2020 123 109716 10.1016/j.biopha.2019.109716 31896067

상세보기

LOADING...

활용도 분석정보

상세보기

다운로드

내보내기

활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
더보기 버튼을 클릭하시면 더 많은 관련자료를 살펴볼 수 있습니다.

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증