J Shanghai Jiaotong Univ Sci

Journal of Shanghai Jiaotong University(Science) >

2021 , Vol. 26 >Issue 1: 40 - 46

DOI: https://doi.org/10.1007/s12204-021-2258-8

Medicine-Engineering Interdisciplinary Research

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

Expand
  • (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 published: 2021-01-19

Fold

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)

Cite this article

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]. Journal of Shanghai Jiaotong University(Science), 2021 , 26(1) : 40 -46 . DOI: 10.1007/s12204-021-2258-8

References

[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.

Options
Outlines

/

〈 〉