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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2019 [J]. CA: A Cancer Journal for Clinicians, 2019, 69(1): 7–34.
HERBST R S, MORGENSZTERN D, BOSHOFF C. The biology and management of non-small cell lung cancer [J]. Nature, 2018, 553: 446–454.
HIRSCH F R, SUDA K, WIENS J, et al. New and emerging targeted treatments in advanced non-small-cell lung cancer [J]. The Lancet, 2016, 388(10048): 1012–1024.
LUNDIN A, DRISCOLL B. Lung cancer stem cells: Progress and prospects [J]. Cancer Letters, 2013, 338(1): 89–93.
KLONISCH T, WIECHEC E, HOMBACH-KLONISCH S, et al. Cancer stem cell markers in common cancers: Therapeutic implications [J]. Trends in Molecular Medicine, 2008, 14(10): 450–460.
CHAMBERS I, COLBY D, ROBERTSON M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells [J]. Cell, 2003, 113(5): 643–655.
MITSUI K, TOKUZAWA Y, ITOH H, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells [J]. Cell, 2003, 113(5): 631–642.
VAN SCHAIJIK B, DAVIS P F, WICKREMESEKERA A C, et al. Subcellular localisation of the stem cell markers OCT4, SOX2, NANOG, KLF4 and c-MYC in cancer: A review [J]. Journal of Clinical Pathology, 2018, 71: 88–91.
VILLODRE E S, KIPPER F C, PEREIRA M B, et al. Roles of OCT4 in tumorigenesis, cancer therapy resistance and prognosis [J]. Cancer Treatment Reviews, 2016, 51: 1–9.
ZHANG X Y, DONG Q G, HUANG J S, et al. The expression of stem cell-related indicators as a prognostic factor in human lung adenocarcinoma [J]. Journal of Surgical Oncology, 2010, 102(7): 856–862.
ZHANG X Y, ZHANG Y W, XU J L, et al. Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes enhances the killing effect of cytotoxic T lymphocytes on tumor stem-like cells derived from cisplatin-resistant lung cancer cells [J]. Journal of Cancer, 2018, 9(2): 367–374.
ZHANG X Y, HU F, LI C H, et al. OCT4&SOX2-specific cytotoxic T lymphocytes plus programmed cell death protein 1 inhibitor presented with synergistic effect on killing lung cancer stem-like cells in vitro and treating drug-resistant lung cancer mice in vivo [J]. Journal of Cellular Physiology, 2019, 234(5): 6758–6768.
LI R, HUANG J S, MA M L, et al. Two-stage induced differentiation of OCT4+/Nanog+ stem-like cells in lung adenocarcinoma [J]. Oncotarget, 2016, 7(42): 68360–68370.
MATIKAS A, SYRIGOS K N, AGELAKI S. Circulating biomarkers in non-small-cell lung cancer: Current status and future challenges [J]. Clinical Lung Cancer, 2016, 17(6): 507–516.
PAOLETTI C, HAYES D F. Circulating tumor cells [M]//STEARNS V. Advances in Experiment Medicine and Biology. Cham, Switzerland: Springer, 2016: 235–258.
CHUDASAMA D, BARR J, BEESON J, et al. Detection of circulating tumour cells and survival of patients with non-small cell lung cancer [J]. Anticancer Research, 2017, 37: 169–173.
HEEKE S, MOGRABI B, ALIX-PANABIÈRES C, et al. Never travel alone: The crosstalk of circulating tumor cells and the blood microenvironment [J]. Cells, 2019, 8(7): 714.
PRABAVATHY D, RAMADOSS N. Heterogeneity of small cell lung cancer stem cells [M]//BIRBRAIR A. Stem cells heterogeneity in cancer. Cham, Switzerland: Springer, 2019: 41–57.
NEL I, JEHN U, GAULER T, et al. Individual profiling of circulating tumor cell composition in patients with non-small cell lung cancer receiving platinum based treatment [J]. Translational Lung Cancer Research, 2014, 3(2): 100–106.
MOHIUDDIN I S, WEI S J, KANG M H. Role of OCT4 in cancer stem-like cells and chemotherapy resistance [J]. BBA-Molecular Basis of Disease, 2020, 1866(4): 165432.
JEN J, TANG Y A, LU Y H, et al. Oct4 transcriptionally regulates the expression of long non-coding RNAs NEAT1 and MALAT1 to promote lung cancer progression [J]. Molecular Cancer, 2017, 16(1): 104.
KOBAYASHI I, TAKAHASHI F, NURWIDYA F, et al. Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells [J]. Biochemical and Biophysical Research Communications, 2016, 473(1): 125–132.
LI S, CHEN Q, LI H, et al. Mesenchymal circulating tumor cells (CTCs) and OCT4 mRNA expression in CTCs for prognosis prediction in patients with non-small-cell lung cancer [J]. Clinical and Translational Oncology, 2017, 19: 1147–1153.
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.
GANDARA D R, PAUL S M, KOWANETZ M, et al. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab [J]. Nature Medicine, 2018, 24: 1441–1448.
GUO J C, LI C Q, WANG Q Y, et al. Protein-coding genes combined with long non-coding RNAs predict prognosis in esophageal squamous cell carcinoma patients as a novel clinical multi-dimensional signature [J]. Molecular BioSystems, 2016, 12(11): 3467–3477.
MATSUBARA J, HONDA K, ONO M, et al. Identification of adipophilin as a potential plasma biomarker for colorectal cancer using label-free quantitative mass spectrometry and protein microarray [J]. Cancer Epidemiology, Biomarkers & Prevention, 2011, 20(10): 2195–2203.
MORRISSEY J J, MOBLEY J, FIGENSHAU R S, et al. Urine Aquaporin 1 and Perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer [J]. Mayo Clinic Proceedings, 2015, 90(1): 35–42.
AMBROSIO M R, PICCALUGA P P, PONZONI M, et al. The alteration of lipid metabolism in Burkitt lymphoma identifies a novel marker: Adipophilin [J]. PLoS One, 2012, 7(8): e44315.
ZHANG X D, LI W, ZHANG N, et al. Identification of adipophilin as a potential diagnostic tumor marker for lung adenocarcinoma [J]. International Journal of Clinical and Experimental Medicine, 2014, 7(4): 1190–1196.
CONTE M, FRANCESCHI C, SANDRI M, et al. Perilipin 2 and age-related metabolic diseases: A new perspective [J]. Trends in Endocrinology & Metabolism, 2016, 27(12): 893–903.
the National Natural Science Foundation of China (No. 81773273)
About this article
Cite this article
Yan, B., Fu, S., Chang, Y. et al. 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. Shanghai Jiaotong Univ. (Sci.) 26, 40–46 (2021). https://doi.org/10.1007/s12204-021-2258-8
- non-small cell lung cancer (NSCLC)
- octamer-binding transcription factor-4 (OCT4)
- circulating tumour cells (CTCs)
- whole exome sequencing (WES)
- R 734.2