Mutational Analysis of OCT4+ and OCT4- Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

doi:10.1007/s12204-021-2258-8

J Shanghai Jiaotong Univ Sci ›› 2021, Vol. 26 ›› Issue (1): 40-46.doi: 10.1007/s12204-021-2258-8

Mutational Analysis of OCT4⁺ and OCT4^- Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

YAN Bo (颜波), FU Shijie (傅世杰), CHANG Yuanyuan (常媛媛), GU Aiqin (顾爱琴), DONG Qianggang (董强刚), LI Rong (李榕)

(1. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China;
2. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China;
3. Cancer Stem Cell Research Group, Shanghai Jiao Tong University Cancer Institute, Shanghai 200032, China)

出版日期:2021-02-28 发布日期:2021-01-19
通讯作者: DONG Qianggang (董强刚), LI Rong (李榕) E-mail:dongqianggang@icell.com.cn, xkyylirong@163.com

Mutational Analysis of OCT4⁺ and OCT4^- Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

YAN Bo (颜波), FU Shijie (傅世杰), CHANG Yuanyuan (常媛媛), GU Aiqin (顾爱琴), DONG Qianggang (董强刚), LI Rong (李榕)

(1. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China;
2. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China;
3. Cancer Stem Cell Research Group, Shanghai Jiao Tong University Cancer Institute, Shanghai 200032, China)

Online:2021-02-28 Published:2021-01-19
Contact: DONG Qianggang (董强刚), LI Rong (李榕) E-mail:dongqianggang@icell.com.cn, xkyylirong@163.com

摘要/Abstract

摘要： Circulating tumour cells (CTCs) were enriched in the peripheral blood of four patients with Stage I non-small cell lung cancer (NSCLC). Octamer-binding transcription factor-4 positive (OCT4⁺) and negative (OCT4^-) CTCs were identified and captured by interphase fluorescence in situ hybridisation (iFISH). Single cell whole exome sequencing (WES) was performed and the corresponding bioinformatics data were analysed. OCT4⁺ cells were successfully detected in peripheral blood collected from all four Stage I lung cancer patients. Moreover,the tumour mutational burden (TMB) values observed for OCT4⁺ samples from the same patients were slightly smaller than those of the OCT4^- samples; the difference was not statistically significant (P > 0.05). Thirteen and six characteristic mutations were found in negative samples and positive samples, respectively. The findings indicate that this methodology provides a potential diagnostic index for the early detection of NSCLC.

关键词: non-small cell lung cancer (NSCLC), octamer-binding transcription factor-4 (OCT4), circulating
tumour cells (CTCs), whole exome sequencing (WES)

Abstract: Circulating tumour cells (CTCs) were enriched in the peripheral blood of four patients with Stage I non-small cell lung cancer (NSCLC). Octamer-binding transcription factor-4 positive (OCT4⁺) and negative (OCT4^-) CTCs were identified and captured by interphase fluorescence in situ hybridisation (iFISH). Single cell whole exome sequencing (WES) was performed and the corresponding bioinformatics data were analysed. OCT4⁺ cells were successfully detected in peripheral blood collected from all four Stage I lung cancer patients. Moreover,the tumour mutational burden (TMB) values observed for OCT4⁺ samples from the same patients were slightly smaller than those of the OCT4^- samples; the difference was not statistically significant (P > 0.05). Thirteen and six characteristic mutations were found in negative samples and positive samples, respectively. The findings indicate that this methodology provides a potential diagnostic index for the early detection of NSCLC.

Key words: non-small cell lung cancer (NSCLC), octamer-binding transcription factor-4 (OCT4), circulating
tumour cells (CTCs), whole exome sequencing (WES)

中图分类号:

R 734.2

YAN Bo (颜波), FU Shijie (傅世杰), CHANG Yuanyuan (常媛媛), GU Aiqin (顾爱琴), DONG Qianggang (董强刚), LI Rong (李榕) . Mutational Analysis of OCT4⁺ and OCT4^- Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients[J]. J Shanghai Jiaotong Univ Sci, 2021, 26(1): 40-46.

参考文献 31

[1]	SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics,2019 [J]. CA: A Cancer Journal for Clinicians,2019, 69(1): 7-34.
[2]	HERBST R S, MORGENSZTERN D, BOSHOFF C.The biology and management of non-small cell lungcancer [J]. Nature, 2018, 553: 446-454.
[3]	HIRSCH F R, SUDA K, WIENS J, et al. New andemerging targeted treatments in advanced non-smallcelllung cancer [J]. The Lancet, 2016, 388(10048):1012-1024.
[4]	LUNDIN A, DRISCOLL B. Lung cancer stem cells:Progress and prospects [J]. Cancer Letters, 2013,338(1): 89-93.
[5]	KLONISCH T, WIECHEC E, HOMBACHKLONISCHS, et al. Cancer stem cell markersin common cancers: Therapeutic implications [J].Trends in Molecular Medicine, 2008, 14(10): 450-460.
[6]	CHAMBERS I, COLBY D, ROBERTSON M, et al.Functional expression cloning of Nanog, a pluripotencysustaining factor in embryonic stem cells [J].Cell, 2003, 113(5): 643-655.
[7]	MITSUI K, TOKUZAWA Y, ITOH H, et al. Thehomeoprotein Nanog is required for maintenance ofpluripotency in mouse epiblast and ES cells [J]. Cell,2003, 113(5): 631-642.
[8]	VAN SCHAIJIK B, DAVIS P F, WICKREMESEKERAA C, et al. Subcellular localisation of the stem cellmarkers OCT4, SOX2, NANOG, KLF4 and c-MYC incancer: A review [J]. Journal of Clinical Pathology,2018, 71: 88-91.
[9]	VILLODRE E S, KIPPER F C, PEREIRA M B, etal. Roles of OCT4 in tumorigenesis, cancer therapy resistanceand prognosis [J]. Cancer Treatment Reviews,2016, 51: 1-9.
[10]	ZHANG X Y, DONG Q G, HUANG J S, et al. Theexpression of stem cell-related indicators as a prognosticfactor in human lung adenocarcinoma [J]. Journalof Surgical Oncology, 2010, 102(7): 856-862.
[11]	ZHANG X Y, ZHANG Y W, XU J L, et al. Antigenpresentation of the Oct4 and Sox2 peptides byCD154-activated B lymphocytes enhances the killingeffect of cytotoxic T lymphocytes on tumor stem-likecells derived from cisplatin-resistant lung cancer cells[J]. Journal of Cancer, 2018, 9(2): 367-374.
[12]	ZHANG X Y, HU F, LI C H, et al. OCT4&SOX2-specific cytotoxic T lymphocytes plus programmed celldeath protein 1 inhibitor presented with synergistic effecton killing lung cancer stem-like cells in vitro andtreating drug-resistant lung cancer mice in vivo [J].Journal of Cellular Physiology, 2019, 234(5): 6758-6768.
[13]	LI R, HUANG J S, MA M L, et al. Two-stage induceddifferentiation of OCT4+/Nanog+ stem-like cells inlung adenocarcinoma [J]. Oncotarget, 2016, 7(42):68360-68370.
[14]	MATIKAS A, SYRIGOS K N, AGELAKI S. Circulatingbiomarkers in non-small-cell lung cancer: Currentstatus and future challenges [J]. Clinical Lung Cancer,2016, 17(6): 507-516.
[15]	PAOLETTI C, HAYES D F. Circulating tumor cells[M]//STEARNS V. Advances in Experiment Medicineand Biology. Cham, Switzerland: Springer, 2016: 235-258.
[16]	CHUDASAMA D, BARR J, BEESON J, et al. Detectionof circulating tumour cells and survival of patientswith non-small cell lung cancer [J]. AnticancerResearch, 2017, 37: 169-173.
[17]	HEEKE S, MOGRABI B, ALIX-PANABI`ERES C, etal. Never travel alone: The crosstalk of circulating tumorcells and the blood microenvironment [J]. Cells,2019, 8(7): 714.
[18]	PRABAVATHY D, RAMADOSS N. Heterogeneity ofsmall cell lung cancer stem cells [M]// BIRBRAIR A.Stem cells heterogeneity in cancer. Cham, Switzerland:Springer, 2019: 41-57.
[19]	NEL I, JEHN U, GAULER T, et al. Individual profilingof circulating tumor cell composition in patientswith non-small cell lung cancer receiving platinumbased treatment [J]. Translational Lung Cancer Research,2014, 3(2): 100-106.
[20]	MOHIUDDIN I S, WEI S J, KANG M H. Role ofOCT4 in cancer stem-like cells and chemotherapy resistance[J]. BBA-Molecular Basis of Disease, 2020,1866(4): 165432.
[21]	JEN J, TANG Y A, LU Y H, et al. Oct4 transcriptionallyregulates the expression of long non-coding RNAsNEAT1 and MALAT1 to promote lung cancer progression[J]. Molecular Cancer, 2017, 16(1): 104.
[22]	KOBAYASHI I, TAKAHASHI F, NURWIDYA F, etal. Oct4 plays a crucial role in the maintenance ofgefitinib-resistant lung cancer stem cells [J]. Biochemicaland Biophysical Research Communications, 2016,473(1): 125-132.
[23]	LI S, CHEN Q, LI H, et al. Mesenchymal circulatingtumor cells (CTCs) and OCT4 mRNA expression inCTCs for prognosis prediction in patients with nonsmall-cell lung cancer [J]. Clinical and TranslationalOncology, 2017, 19: 1147-1153.
[24]	RIZVI N A, HELLMANN M D, SNYDER A, et al.Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer [J]. Science,2015, 348(6230): 124-128.
[25]	GANDARA D R, PAUL S M, KOWANETZ M, et al.Blood-based tumor mutational burden as a predictorof clinical benefit in non-small-cell lung cancer patientstreated with atezolizumab [J]. Nature Medicine, 2018,24: 1441-1448.
[26]	GUO J C, LI C Q, WANG Q Y, et al. Protein-codinggenes combined with long non-coding RNAs predictprognosis in esophageal squamous cell carcinoma patientsas a novel clinical multi-dimensional signature[J]. Molecular BioSystems, 2016, 12(11): 3467-3477.
[27]	MATSUBARA J, HONDA K, ONO M, et al. Identificationof adipophilin as a potential plasma biomarkerfor colorectal cancer using label-free quantitative massspectrometry and protein microarray [J]. Cancer Epidemiology,Biomarkers & Prevention, 2011, 20(10):2195-2203.
[28]	MORRISSEY J J, MOBLEY J, FIGENSHAU R S, etal. Urine Aquaporin 1 and Perilipin 2 differentiate renalcarcinomas from other imaged renal masses andbladder and prostate cancer [J]. Mayo Clinic Proceedings,2015, 90(1): 35-42.
[29]	AMBROSIO M R, PICCALUGA P P, PONZONI M,et al. The alteration of lipid metabolism in Burkittlymphoma identifies a novel marker: Adipophilin [J].PLoS One, 2012, 7(8): e44315.
[30]	ZHANG X D, LI W, ZHANG N, et al. Identificationof adipophilin as a potential diagnostic tumor markerfor lung adenocarcinoma [J]. International Journal ofClinical and Experimental Medicine, 2014, 7(4): 1190-1196.
[31]	CONTE M, FRANCESCHI C, SANDRI M, et al. Perilipin2 and age-related metabolic diseases: A new perspective[J]. Trends in Endocrinology & Metabolism,2016, 27(12): 893-903.

Mutational Analysis of OCT4⁺ and OCT4^- Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

Mutational Analysis of OCT4⁺ and OCT4^- Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 31

相关文章 0

编辑推荐

Metrics

本文评价