Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Samples
2.2. Spiking Experiments
2.3. Gene Expression Analysis
2.4. Calculation of the Cut-Off Threshold Values
2.5. Statistical Analysis
3. Results
3.1. Patients and Samples
3.2. Spiking Experiments
3.3. Lung Cancer Markers in Controls and NSCLC Blood Samples
3.4. CTC-Related Markers and Patient Outcome
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef]
- Allemani, C.; Matsuda, T.; Di Carlo, V.; Harewood, R.; Matz, M.; Niksic, M.; Bonaventure, A.; Valkov, M.; Johnson, C.J.; Esteve, J.; et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): Analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 2018, 391, 1023–1075. [Google Scholar] [CrossRef] [Green Version]
- Howlader, N.; Noone, A.M.; Krapcho, M.F.; Miller, D.; Brest, A.; Yu, M.; Ruhl, J.; Tatalovich, Z.; Mariotto, A.; Lewis, D.R.; et al. SEER Cancer Statistics Review, 1975–2017. Available online: https://seer.cancer.gov/csr/1975_2017/ (accessed on 1 October 2021).
- Carnio, S.; Novello, S.; Papotti, M.; Loiacono, M.; Scagliotti, G.V. Prognostic and predictive biomarkers in early stage non-small cell lung cancer: Tumor based approaches including gene signatures. Transl. Lung Cancer Res. 2013, 2, 372–381. [Google Scholar] [CrossRef] [PubMed]
- Uramoto, H.; Tanaka, F. Recurrence after surgery in patients with NSCLC. Transl. Lung Cancer Res. 2014, 3, 242–249. [Google Scholar] [CrossRef] [PubMed]
- Horton, C.E.; Kamal, M.; Leslie, M.; Zhang, R.; Tanaka, T.; Razaq, M. Circulating Tumor Cells Accurately Predicting Progressive Disease After Treatment in a Patient with Non-small Cell Lung Cancer Showing Response on Scans. Anticancer Res. 2018, 38, 1073–1076. [Google Scholar] [CrossRef] [PubMed]
- Nichols, L.; Saunders, R.; Knollmann, F.D. Causes of death of patients with lung cancer. Arch. Pathol. Lab. Med. 2012, 136, 1552–1557. [Google Scholar] [CrossRef] [PubMed]
- Kuhn, P.; Bethel, K. A fluid biopsy as investigating technology for the fluid phase of solid tumors. Phys. Biol. 2012, 9, 010301. [Google Scholar] [CrossRef] [Green Version]
- Alberter, B.; Klein, C.A.; Polzer, B. Single-cell analysis of CTCs with diagnostic precision: Opportunities and challenges for personalized medicine. Expert. Rev. Mol. Diagn. 2016, 16, 25–38. [Google Scholar] [CrossRef]
- Arbour, K.C.; Riely, G.J. Systemic Therapy for Locally Advanced and Metastatic Non-Small Cell Lung Cancer: A Review. JAMA 2019, 322, 764–774. [Google Scholar] [CrossRef]
- Abbosh, C.; Birkbak, N.J.; Wilson, G.A.; Jamal-Hanjani, M.; Constantin, T.; Salari, R.; Le Quesne, J.; Moore, D.A.; Veeriah, S.; Rosenthal, R.; et al. Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 2018, 554, 264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nicolazzo, C.; Raimondi, C.; Mancini, M.; Caponnetto, S.; Gradilone, A.; Gandini, O.; Mastromartino, M.; Del Bene, G.; Prete, A.; Longo, F.; et al. Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab. Sci. Rep. 2016, 6, 31726. [Google Scholar] [CrossRef]
- Syrigos, K.; Fiste, O.; Charpidou, A.; Grapsa, D. Circulating tumor cells count as a predictor of survival in lung cancer. Crit. Rev. Oncol. Hematol. 2018, 125, 60–68. [Google Scholar] [CrossRef]
- Maheswaran, S.; Sequist, L.V.; Nagrath, S.; Ulkus, L.; Brannigan, B.; Collura, C.V.; Inserra, E.; Diederichs, S.; Iafrate, A.J.; Bell, D.W.; et al. Detection of mutations in EGFR in circulating lung-cancer cells. N. Engl. J. Med. 2008, 359, 366–377. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Q.; Nong, J.; Wang, J.; Yan, Z.; Yi, L.; Gao, X.; Liu, Z.; Zhang, H.; Zhang, S. Isolation of circulating tumor cells and detection of EGFR mutations in patients with non-small-cell lung cancer. Oncol. Lett. 2019, 17, 3799–3807. [Google Scholar] [CrossRef]
- Chudziak, J.; Burt, D.J.; Mohan, S.; Rothwell, D.G.; Mesquita, B.; Antonello, J.; Dalby, S.; Ayub, M.; Priest, L.; Carter, L.; et al. Clinical evaluation of a novel microfluidic device for epitope-independent enrichment of circulating tumour cells in patients with small cell lung cancer. Analyst 2016, 141, 669–678. [Google Scholar] [CrossRef]
- Janning, M.; Kobus, F.; Babayan, A.; Wikman, H.; Velthaus, J.L.; Bergmann, S.; Schatz, S.; Falk, M.; Berger, L.A.; Bottcher, L.M.; et al. Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1/PD-L1 Inhibitors. Cancers 2019, 11, 835. [Google Scholar] [CrossRef] [Green Version]
- Miller, M.C.; Robinson, P.S.; Wagner, C.; O’Shannessy, D.J. The Parsortix Cell Separation System-A versatile liquid biopsy platform. Cytometry A 2018, 93, 1234–1239. [Google Scholar] [CrossRef]
- Obermayr, E.; Maritschnegg, E.; Agreiter, C.; Pecha, N.; Speiser, P.; Helmy-Bader, S.; Danzinger, S.; Krainer, M.; Singer, C.; Zeillinger, R. Efficient leukocyte depletion by a novel microfluidic platform enables the molecular detection and characterization of circulating tumor cells. Oncotarget 2018, 9, 812–823. [Google Scholar] [CrossRef] [Green Version]
- Obermayr, E.; Agreiter, C.; Schuster, E.; Fabikan, H.; Weinlinger, C.; Baluchova, K.; Hamilton, G.; Hochmair, M.; Zeillinger, R. Molecular Characterization of Circulating Tumor Cells Enriched by A Microfluidic Platform in Patients with Small-Cell Lung Cancer. Cells 2019, 8, 880. [Google Scholar] [CrossRef] [Green Version]
- Stathopoulou, A.; Ntoulia, M.; Perraki, M.; Apostolaki, S.; Mavroudis, D.; Malamos, N.; Georgoulias, V.; Lianidou, E.S. A highly specific real-time RT-PCR method for the quantitative determination of CK-19 mRNA positive cells in peripheral blood of patients with operable breast cancer. Int. J. Cancer 2006, 119, 1654–1659. [Google Scholar] [CrossRef]
- Mikhitarian, K.; Martin, R.H.; Ruppel, M.B.; Gillanders, W.E.; Hoda, R.; Schutte del, H.; Callahan, K.; Mitas, M.; Cole, D.J. Detection of mammaglobin mRNA in peripheral blood is associated with high grade breast cancer: Interim results of a prospective cohort study. BMC Cancer 2008, 8, 55. [Google Scholar] [CrossRef] [Green Version]
- Kassambara, A.; Kosinski, M.; Przemyslaw, B.; Scheipl, F. Survminer: Drawing Survival Curves Using “ggplot2.”. Available online: https://cran.r-project.org/package=survminer (accessed on 1 September 2021).
- Papadaki, M.A.; Sotiriou, A.I.; Vasilopoulou, C.; Filika, M.; Aggouraki, D.; Tsoulfas, P.G.; Apostolopoulou, C.A.; Rounis, K.; Mavroudis, D.; Agelaki, S. Optimization of the Enrichment of Circulating Tumor Cells for Downstream Phenotypic Analysis in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1 Immunotherapy. Cancers 2020, 12, 1556. [Google Scholar] [CrossRef]
- Neves, R.P.L.; Ammerlaan, W.; Andree, K.C.; Bender, S.; Cayrefourcq, L.; Driemel, C.; Koch, C.; Luetke-Eversloh, M.V.; Oulhen, M.; Rossi, E.; et al. Proficiency Testing to Assess Technical Performance for CTC-Processing and Detection Methods in CANCER-ID. Clin. Chem. 2021, 67, 631–641. [Google Scholar] [CrossRef]
- Lindsay, C.R.; Blackhall, F.H.; Carmel, A.; Fernandez-Gutierrez, F.; Gazzaniga, P.; Groen, H.J.M.; Hiltermann, T.J.N.; Krebs, M.G.; Loges, S.; Lopez-Lopez, R.; et al. EPAC-lung: Pooled analysis of circulating tumour cells in advanced non-small cell lung cancer. Eur. J. Cancer 2019, 117, 60–68. [Google Scholar] [CrossRef] [Green Version]
- Papadaki, M.A.; Messaritakis, I.; Fiste, O.; Souglakos, J.; Politaki, E.; Kotsakis, A.; Georgoulias, V.; Mavroudis, D.; Agelaki, S. Assessment of the Efficacy and Clinical Utility of Different Circulating Tumor Cell (CTC) Detection Assays in Patients with Chemotherapy-Naive Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC). Int. J. Mol. Sci. 2021, 22, 925. [Google Scholar] [CrossRef]
- Obermayr, E.; Reiner, A.; Brandt, B.; Braicu, E.I.; Reinthaller, A.; Loverix, L.; Concin, N.; Woelber, L.; Mahner, S.; Sehouli, J.; et al. The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer-A Study of the OVCAD Consortium. Cancers 2021, 13, 2613. [Google Scholar] [CrossRef]
- Obermayr, E.; Castillo-Tong, D.C.; Pils, D.; Speiser, P.; Braicu, I.; Van Gorp, T.; Mahner, S.; Sehouli, J.; Vergote, I.; Zeillinger, R. Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance—A study of the OVCAD consortium. Gynecol. Oncol. 2013, 128, 15–21. [Google Scholar] [CrossRef]
- Markou, A.; Lazaridou, M.; Paraskevopoulos, P.; Chen, S.; Swierczewska, M.; Budna, J.; Kuske, A.; Gorges, T.M.; Joosse, S.A.; Kroneis, T.; et al. Multiplex Gene Expression Profiling of In Vivo Isolated Circulating Tumor Cells in High-Risk Prostate Cancer Patients. Clin. Chem. 2018, 64, 297–306. [Google Scholar] [CrossRef]
- Guadagni, S.; Clementi, M.; Masedu, F.; Fiorentini, G.; Sarti, D.; Deraco, M.; Kusamura, S.; Papasotiriou, I.; Apostolou, P.; Aigner, K.R.; et al. A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer. Int. J. Mol. Sci. 2020, 21, 4813. [Google Scholar] [CrossRef]
- Antonarakis, E.S.; Lu, C.; Luber, B.; Wang, H.; Chen, Y.; Zhu, Y.; Silberstein, J.L.; Taylor, M.N.; Maughan, B.L.; Denmeade, S.R.; et al. Clinical Significance of Androgen Receptor Splice Variant-7 mRNA Detection in Circulating Tumor Cells of Men With Metastatic Castration-Resistant Prostate Cancer Treated With First- and Second-Line Abiraterone and Enzalutamide. J. Clin. Oncol. 2017, 35, 2149–2156. [Google Scholar] [CrossRef]
- Jacot, W.; Cottu, P.; Berger, F.; Dubot, C.; Venat-Bouvet, L.; Lortholary, A.; Bourgeois, H.; Bollet, M.; Servent, V.; Luporsi, E.; et al. Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: The CirCe T-DM1 trial. Breast Cancer Res. 2019, 21, 121. [Google Scholar] [CrossRef] [PubMed]
- Park, E.; Park, S.Y.; Sun, P.L.; Jin, Y.; Kim, J.E.; Jheon, S.; Kim, K.; Lee, C.T.; Kim, H.; Chung, J.H. Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma. Oncotarget 2016, 7, 42502–42512. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chebouti, I.; Kuhlmann, J.D.; Buderath, P.; Weber, S.; Wimberger, P.; Bokeloh, Y.; Hauch, S.; Kimmig, R.; Kasimir-Bauer, S. ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer. Oncotarget 2017, 8, 24303–24313. [Google Scholar] [CrossRef] [PubMed]
- Kuhlmann, J.D.; Wimberger, P.; Bankfalvi, A.; Keller, T.; Scholer, S.; Aktas, B.; Buderath, P.; Hauch, S.; Otterbach, F.; Kimmig, R.; et al. ERCC1-positive circulating tumor cells in the blood of ovarian cancer patients as a predictive biomarker for platinum resistance. Clin. Chem. 2014, 60, 1282–1289. [Google Scholar] [CrossRef] [Green Version]
- Jeter, C.R.; Yang, T.; Wang, J.; Chao, H.P.; Tang, D.G. Concise Review: NANOG in Cancer Stem Cells and Tumor Development: An Update and Outstanding Questions. Stem Cells 2015, 33, 2381–2390. [Google Scholar] [CrossRef] [Green Version]
- Yin, X.; Li, Y.W.; Zhang, B.H.; Ren, Z.G.; Qiu, S.J.; Yi, Y.; Fan, J. Coexpression of stemness factors Oct4 and Nanog predict liver resection. Ann. Surg. Oncol. 2012, 19, 2877–2887. [Google Scholar] [CrossRef]
- Meng, H.M.; Zheng, P.; Wang, X.Y.; Liu, C.; Sui, H.M.; Wu, S.J.; Zhou, J.; Ding, Y.Q.; Li, J. Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol. Ther. 2010, 9, 295–302. [Google Scholar] [CrossRef] [Green Version]
- Lu, Y.; Zhu, H.; Shan, H.; Lu, J.; Chang, X.; Li, X.; Lu, J.; Fan, X.; Zhu, S.; Wang, Y.; et al. Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells. Cancer Lett. 2013, 340, 113–123. [Google Scholar] [CrossRef]
- Chang, B.; Park, M.J.; Choi, S.I.; In, K.H.; Kim, C.H.; Lee, S.H. NANOG as an adverse predictive marker in advanced non-small cell lung cancer treated with platinum-based chemotherapy. OncoTargets Ther. 2017, 10, 4625–4633. [Google Scholar] [CrossRef] [Green Version]
- Ling, K.; Jiang, L.; Liang, S.; Kwong, J.; Yang, L.; Li, Y.; Ping, Y.; Deng, Q.; Liang, Z. Nanog interaction with the androgen receptor signaling axis induce ovarian cancer stem cell regulation: Studies based on the CRISPR/Cas9 system. J. Ovarian Res. 2018, 11, 36. [Google Scholar] [CrossRef]
- Tada, H.; Takahashi, H.; Kawabata-Iwakawa, R.; Nagata, Y.; Uchida, M.; Shino, M.; Ida, S.; Mito, I.; Matsuyama, T.; Chikamatsu, K. Molecular phenotypes of circulating tumor cells and efficacy of nivolumab treatment in patients with head and neck squamous cell carcinoma. Sci. Rep. 2020, 10, 21573. [Google Scholar] [CrossRef]
- Tada, H.; Takahashi, H.; Kuwabara-Yokobori, Y.; Shino, M.; Chikamatsu, K. Molecular profiling of circulating tumor cells predicts clinical outcome in head and neck squamous cell carcinoma. Oral Oncol. 2020, 102, 104558. [Google Scholar] [CrossRef]
- Lei, Y.; Wang, X.; Sun, H.; Fu, Y.; Tian, Y.; Yang, L.; Wang, J.; Xia, F. Association of Preoperative NANOG-Positive Circulating Tumor Cell Levels with Recurrence of Hepatocellular Carcinoma. Front. Oncol. 2021, 11, 601668. [Google Scholar] [CrossRef]
- Li, Y.; Rogoff, H.A.; Keates, S.; Gao, Y.; Murikipudi, S.; Mikule, K.; Leggett, D.; Li, W.; Pardee, A.B.; Li, C.J. Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc. Natl. Acad. Sci. USA 2015, 112, 1839–1844. [Google Scholar] [CrossRef] [Green Version]
- Barzegar Behrooz, A.; Syahir, A.; Ahmad, S. CD133: Beyond a cancer stem cell biomarker. J. Drug Target. 2019, 27, 257–269. [Google Scholar] [CrossRef] [Green Version]
- Nel, I.; Jehn, U.; Gauler, T.; Hoffmann, A.C. Individual profiling of circulating tumor cell composition in patients with non-small cell lung cancer receiving platinum based treatment. Transl. Lung Cancer Res. 2014, 3, 100–106. [Google Scholar] [CrossRef]
- Obermayr, E.; Sanchez-Cabo, F.; Tea, M.K.; Singer, C.F.; Krainer, M.; Fischer, M.B.; Sehouli, J.; Reinthaller, A.; Horvat, R.; Heinze, G.; et al. Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients. BMC Cancer 2010, 10, 666. [Google Scholar] [CrossRef] [Green Version]
- Katseli, A.; Maragos, H.; Nezos, A.; Syrigos, K.; Koutsilieris, M. Multiplex PCR-based detection of circulating tumor cells in lung cancer patients using CK19, PTHrP, and LUNX specific primers. Clin. Lung Cancer 2013, 14, 513–520. [Google Scholar] [CrossRef]
- Li, J.; Shi, S.B.; Shi, W.L.; Wang, Y.; Yu, L.C.; Zhu, L.R.; Ge, L.P. LUNX mRNA-positive cells at different time points predict prognosis in patients with surgically resected nonsmall cell lung cancer. Transl. Res. 2014, 163, 27–35. [Google Scholar] [CrossRef]
Characteristics | n (%) |
---|---|
Age (years): | |
Mean (median) | 66.4 (66.0) |
Range | 46.0 - 89.0 |
Gender: | |
Male | 60 (50.4) |
Female | 59 (49.6) |
Tobacco abuse: | |
Current smokers | 35 (29.4) |
Former smokers | 36 (30.3) |
Never smokers | 15 (12.6) |
Unknown | 33 (27.7) |
Outcome at study completion: | |
Dead | 25 (21.0) |
Alive | 94 (79.0) |
Blood draw for CTCs: | |
At primary diagnosis | 67 (56.8) |
At progression/recurrence | 39 (32.8) |
Unknown | 12 (10.2) |
Threshold | Healthy | NSCLC | ||||
---|---|---|---|---|---|---|
All Donors (n = 30) | All Patients (n = 118) | Primary Diagnosis (n = 67) | Progression (n = 39) | p | ||
Overall | 2 (6.7%) | 85 (72.0%) | 55 (82.1%) | 21 (53.8%) | 0.002 | |
Epithelial cell-specific | ||||||
EpCAM | 30.7 | 0 | 54 (45.7%) | 36 (53.7%) | 10 (25.6%) | 0.005 |
CK19 | 32.7 | 0 | 15 (12.7%) | 11 (16.4%) | 3 (7.7%) | 0.201 |
Ciliated epithelial-cell specific | ||||||
BPIFA1 | 40.0 | 0 | 2 (1.7%) | 1 (1.5%) | 1 (2.6%) | 0.696 |
Cancer stem cell-related | ||||||
NANOG | 22.8 | 1 (3.3%) | 34 (28.8%) | 23 (34.3%) | 8 (20.5%) | 0.132 |
PROM1 | 29.2 | 1 (3.3%) | 16 (13.6%) | 10 (14.9%) | 4 (10.3%) | 0.494 |
MET | 26.9 | 0 | 6 (5.1%) | 4 (6.0%) | 1 (2.6%) | 0.425 |
Cancer-related | ||||||
UCHL1 | 28.5 | 0 | 13 (11.0%) | 10 (14.9%) | 2 (5.1%) | 0.125 |
GRP | 40.0 | 0 | 3 (2.5%) | 2 (3.0%) | 1 (2.6%) | 0.883 |
TERT | 31.0 | 0 | 37 (31.4%) | 9 (13.4%) | 4 (10.3%) | 0.631 |
CDH5 | 26.2 | 0 | 8 (6.8%) | 6 (9.0%) | 2 (5.1%) | 0.472 |
EMT-related | ||||||
FAM83A | 40.0 | 0 | 23 (19.5%) | 16 (23.4%) | 4 (10.3%) | 0.084 |
PTHLH | 28.9 | 0 | 8 (6.8%) | 5 (7.5%) | 2 (5.1%) | 0.641 |
ERBB3 | 30.9 | 0 | 18 (15.3%) | 12 (17.9%) | 5 (12.8%) | 0.491 |
TWIST | 28.1 | 0 | 9 (7.6%) | 6 (9.0%) | 1 (2.6%) | 0.201 |
Prognostic Cut-Off at Primary Diagnosis | Prognostic Cut-Off at Disease Progression | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Marker | Threshold | Healthy (n = 30) | Patients (n = 67) | HR | 95% CI | p | Threshold | Healthy (n = 30) | Patients (n = 39) | HR | 95% CI | p |
Epithelial cell-specific | ||||||||||||
EpCAM | 28.9 | 0 | 18 (26.9%) | 2.58 | 0.81–8.27 | 0.056 | 28.2 | 0 | 3 (7.7%) | 9.39 | 0.21–422.74 | <0.001 |
CK19 | 37.2 | 2 | 30 (44.8%) | 2.92 | 1.04–8.19 | 0.040 | 32.6 | 0 | 2 (5.1%) | 2.03 | 0.12–33.09 | 0.480 |
Ciliated epithelial cell-specific | ||||||||||||
BPIFA1 | NA. | NA | ||||||||||
Cancer stem cell-related | ||||||||||||
NANOG | 22.7 | 0 | 22 (32.8%) | 3.21 | 1.02–10.14 | 0.016 | 22.6 | 0 | 8 (20.5%) | 4.17 | 0.72–24.14 | 0.025 |
PROM1 | 28.4 | 0 | 7 (10.4%) | 4.23 | 0.65–27.56 | 0.007 | 28.9 | 0 | 4 (10.2%) | 4.77 | 0.29–78.94 | 0.032 |
MET | 31.5 | 2 | 23 (34.3%) | 1.84 | 0.62–5.44 | 0.230 | 31.4 | 2 | 12 (30.1%) | 3.47 | 0.49–24.54 | 0.059 |
Cancer-related | ||||||||||||
UCHL1 | 29.5 | 2 | 18 (26.9%) | 0.43 | 0.14–1.34 | 0.250 | 31.9 | 6 | 15 (38.5%) | 3.13 | 0.78–12.51 | 0.110 |
GRP | NA. | NA | ||||||||||
TERT | 34.0 | 1 | 24 (35.8%) | 1.62 | 0.56–4.67 | 0.350 | 30.8 | 0 | 3 (7.7%) | 8.32 | 0.23–304.78 | 0.002 |
CDH5 | 31.1 | 5 | 39 (58.2%) | 0.56 | 0.20–1.59 | 0.260 | 27.5 | 2 | 6 (15.3%) | 4.00 | 0.51–30.96 | 0.037 |
EMT-related | ||||||||||||
FAM83A | 30.2 | 0 | 9 (13.4%) | 0.37 | 0.09–1.45 | 0.310 | 29.5 | 0 | 3 (7.7%) | 9.39 | 0.21–422.74 | <0.001 |
PTHLH | 32.6 | 3 | 22 (32.8%) | 2.48 | 0.83–7.36 | 0.070 | 34.6 | 4 | 16 (41.0%) | 5.63 | 1.31–24.22 | 0.012 |
ERBB3 | 32.3 | 3 | 22 (32.8%) | 0.41 | 0.14–1.16 | 0.150 | 30.3 | 0 | 3 (7.7%) | 9.39 | 0.21–422.74 | <0.001 |
TWIST | 29.7 | 0 | 18 (26.9%) | 1.75 | 0.56–5.42 | 0.280 | 31.0 | 1 | 12 (30.1%) | 2.59 | 0.44–15.22 | 0.160 |
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Obermayr, E.; Koppensteiner, N.; Heinzl, N.; Schuster, E.; Holzer, B.; Fabikan, H.; Weinlinger, C.; Illini, O.; Hochmair, M.; Zeillinger, R. Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer. J. Pers. Med. 2021, 11, 1225. https://doi.org/10.3390/jpm11111225
Obermayr E, Koppensteiner N, Heinzl N, Schuster E, Holzer B, Fabikan H, Weinlinger C, Illini O, Hochmair M, Zeillinger R. Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer. Journal of Personalized Medicine. 2021; 11(11):1225. https://doi.org/10.3390/jpm11111225
Chicago/Turabian StyleObermayr, Eva, Nina Koppensteiner, Nicole Heinzl, Eva Schuster, Barbara Holzer, Hannah Fabikan, Christoph Weinlinger, Oliver Illini, Maximilian Hochmair, and Robert Zeillinger. 2021. "Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer" Journal of Personalized Medicine 11, no. 11: 1225. https://doi.org/10.3390/jpm11111225