Identification of Biomarkers for Lung Adenocarcinoma With Qi Deficiency and Phlegm Dampness.
Qi deficiency and phlegm dampness
RNA‐seq
biomarker
lung adenocarcinoma
traditional Chinese medicine
Journal
The clinical respiratory journal
ISSN: 1752-699X
Titre abrégé: Clin Respir J
Pays: England
ID NLM: 101315570
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
revised:
04
08
2023
received:
08
05
2023
accepted:
02
07
2024
medline:
7
8
2024
pubmed:
7
8
2024
entrez:
7
8
2024
Statut:
ppublish
Résumé
Qi deficiency and phlegm dampness (QPD) is one of the most common traditional Chinese medicine (TCM) syndromes in lung adenocarcinoma (LUAD). This study aimed to identify syndrome-specific biomarkers for LUAD with QPD syndrome. Peripheral blood mononuclear cells (PBMCs) from LUAD patients with QPD, LUAD patients with non-QPD (N-QPD), and healthy control (H) were collected and analyzed with RNA-seq to identify differentially expressed genes (DEGs). The area under the receiver operator characteristic curve (AUC) of each DEG was calculated, and the top 10 highest AUC DEGs were validated by qRT-PCR. Logistic regression analysis was used to develop a diagnostic model evaluated with AUC. A total of 135 individuals were enrolled in this study (training set: 15 QPD, 15 N-QPD, 15 H; validation set: 30 QPD, 30 N-QPD, 30 H). A total of 1480 DEGs were identified between QPD and N-QPD. The qRT-PCR results showed that the expression of DDR2 was downregulated, and PPARG was upregulated, which was in line with the finding of the training set. We developed a diagnostic model with these two genes. The AUC of the diagnostic model in the training cohort and validation cohort was 0.891 and 0.777, respectively. We identified the two genes (DDR2 and PPARG) as syndrome-specific biomarkers for LUAD with QPD syndrome and developed a novel diagnostic model, which may help to improve the accuracy and sensibility of clinical diagnosis and provide a new target for natural drug treatment of LUAD.
Sections du résumé
BACKGROUND
BACKGROUND
Qi deficiency and phlegm dampness (QPD) is one of the most common traditional Chinese medicine (TCM) syndromes in lung adenocarcinoma (LUAD). This study aimed to identify syndrome-specific biomarkers for LUAD with QPD syndrome.
METHODS
METHODS
Peripheral blood mononuclear cells (PBMCs) from LUAD patients with QPD, LUAD patients with non-QPD (N-QPD), and healthy control (H) were collected and analyzed with RNA-seq to identify differentially expressed genes (DEGs). The area under the receiver operator characteristic curve (AUC) of each DEG was calculated, and the top 10 highest AUC DEGs were validated by qRT-PCR. Logistic regression analysis was used to develop a diagnostic model evaluated with AUC.
RESULTS
RESULTS
A total of 135 individuals were enrolled in this study (training set: 15 QPD, 15 N-QPD, 15 H; validation set: 30 QPD, 30 N-QPD, 30 H). A total of 1480 DEGs were identified between QPD and N-QPD. The qRT-PCR results showed that the expression of DDR2 was downregulated, and PPARG was upregulated, which was in line with the finding of the training set. We developed a diagnostic model with these two genes. The AUC of the diagnostic model in the training cohort and validation cohort was 0.891 and 0.777, respectively.
CONCLUSIONS
CONCLUSIONS
We identified the two genes (DDR2 and PPARG) as syndrome-specific biomarkers for LUAD with QPD syndrome and developed a novel diagnostic model, which may help to improve the accuracy and sensibility of clinical diagnosis and provide a new target for natural drug treatment of LUAD.
Substances chimiques
Biomarkers, Tumor
0
PPAR gamma
0
PPARG protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13812Subventions
Organisme : Key R & D plan of Zhejiang Province
ID : 2022C03152
Organisme : Key research project of TCM in Zhejiang Province
ID : 2022ZZ006
Organisme : National Natural Science Foundation of China
ID : 82274322
Informations de copyright
© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.
Références
R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer Statistics, 2019,” CA: A Cancer Journal for Clinicians 69 (2019): 7–34, https://doi.org/10.3322/caac.21551.
J. A. Barta, C. A. Powell, and J. P. Wisnivesky, “Global Epidemiology of Lung Cancer,” Annals of Global Health 85 (2019): 8, https://doi.org/10.5334/aogh.2419.
F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” CA: A Cancer Journal for Clinicians 68 (2018): 394–424, https://doi.org/10.3322/caac.21492.
D. Domingues, A. Turner, M. D. Silva, et al., “Immunotherapy and Lung Cancer: Current Developments and Novel Targeted Therapies,” Immunotherapy 6 (2014): 1221–1235, https://doi.org/10.2217/imt.14.82.
H. Lemjabbar‐Alaoui, O. U. Hassan, Y. W. Yang, and P. Buchanan, “Lung Cancer: Biology and Treatment Options,” Biochimica et Biophysica Acta 1856 (2015): 189–210, https://doi.org/10.1016/j.bbcan.2015.08.002.
Q. Ji, Y. Luo, W. Wang, X. Liu, Q. Li, and S. B. Su, “Research Advances in Traditional Chinese Medicine Syndromes in Cancer Patients,” Journal of Integrative Medicine 14 (2016): 12–21, https://doi.org/10.1016/S2095‐4964(16)60237‐6.
F. Qi, L. Zhao, A. Zhou, et al., “The Advantages of Using Traditional Chinese Medicine as an Adjunctive Therapy in the Whole Course of Cancer Treatment Instead of Only Terminal Stage of Cancer,” Bioscience Trends 9 (2015): 16–34, https://doi.org/10.5582/bst.2015.01019.
Z. Liu, Z. Yu, X. OuYang, J. du, X. Lan, and M. Zhao, “Applied Research on Serum Protein Fingerprints for Prediction of Qi Deficiency Syndrome and Phlegm and Blood Stasis in Patients With Non‐Small Cell Lung Cancer,” Journal of Traditional Chinese Medicine 32 (2012): 350–354, https://doi.org/10.1016/s0254‐6272(13)60036‐9.
F. Si, X. Song, R. Chen, et al., “Syndrome and Formula Distribution of Primary Lung Cancer: Literature Study,” Journal of Traditional Chinese Medicine 55 (2014): 1146–1151.
X. Meng, Y. Han, Y. M. Xu, et al., “Study on the Distribution and Combination Law of TCM Syndromes on 180 Casespatients With Advanced Non‐Small Cell Lung Cancer,” China Journal of Traditional Chinese Medicine and Pharmacy. 29, no. 9 (2014): 2978–2982.
K. Q. Chai, J. B. Chen, and G. S. Xu, “Discussion on Four Principles and Four Methods of Chinese Medicine Tumor Syndrome Differentiation and Treatment Based on Combination of Disease and Syndrome,” Journal of Traditional Chinese Medicine 57 (2016): 111–114.
Z. H. Yu, G. S. Xu, J. B. Chen, et al., “Influencing Factor Analysis of Traditional Chinese Medicine Syndrome Differentiation Combined With Epidermal Growth Factor Receptor‐Tyrosine Kinase Inhibitor on Survival of 104 Cases of Advanced Lung Adenocarcinoma Epidermal Growth Factor Receptor Gene‐Sensitive Mutations,” Journal of Traditional Chinese Medicine 60 (2019): 1378–1383.
W. Sumei, L. Shunqin, and W. Wanyin, “Application of Traditional Chinese Medicines as Personalized Therapy in Human Cancers,” The American Journal of Chinese Medicine 46 (2018): 953–970, https://doi.org/10.1142/S0192415X18500507.
L. Li‐zhu, W. Shu‐mei, and Z. Jing‐xu, “Effects of Yiqi Chutan Recipe on Tumor Growth, Survival Time and Expressions of PRDX‐1 and PRDX‐6 in Lewis Lung Carcinoma Model Mice With Pi‐Deficiency Syndrome,” Journal of Traditional Chinese Medicine 31 (2011): 99–103.
W. Chen, J. Lin, T. Yang, et al., “Yifei Sanjie Formula or Placebo With Anlotinib as Second‐Line or Above Treatment for Metastatic Non‐Small‐Cell Lung Cancer: Study Protocol for a Double‐Blind, Placebo‐Controlled Randomized Pilot Study,” Integrative Cancer Therapies 22 (2023): 15347354221151147, https://doi.org/10.1177/15347354221151147.
C. Su, H. Li, Z. Peng, D. Ke, H. Fu, and X. Zheng, “Identification of Plasma RGS18 and PPBP mRNAs as Potential Biomarkers for Gastric Cancer Using Transcriptome Arrays,” Oncology Letters 17 (2018): 247–255, https://doi.org/10.3892/ol.2018.9608.
Z. Fathi, S. A. J. Mousavi, R. Roudi, and F. Ghazi, “Distribution of KRAS, DDR2, and TP53 Gene Mutations in Lung Cancer: An Analysis of Iranian Patients,” PLoS ONE 13 (2018): e0200633, https://doi.org/10.1371/journal.pone.0200633.
S. Sasaki, M. Ueda, T. Iguchi, et al., “DDR2 Expression Is Associated With a High Frequency of Peritoneal Dissemination and Poor Prognosis in Colorectal Cancer,” Anticancer Research 37 (2017): 2587–2591, https://doi.org/10.21873/anticanres.11603.
M. Terashima, Y. Togashi, K. Sato, et al., “Functional Analyses of Mutations in Receptor Tyrosine Kinase Genes in Non‐Small Cell Lung Cancer: Double‐Edged Sword of DDR2,” Clinical Cancer Research 22 (2016): 3663–3671, https://doi.org/10.1158/1078‐0432.CCR‐15‐2093.
H. Yashima, K. Shimizu, T. Araki, et al., “Assessment of DDR2, BRAF, EGFR and KRAS Mutations as Therapeutic Targets in Non‐Adenocarcinoma Lung Cancer Patients,” Molecular and Clinical Oncology 2 (2014): 714–718, https://doi.org/10.3892/mco.2014.302.
D. Savic, R. C. Ramaker, B. S. Roberts, et al., “Distinct Gene Regulatory Programs Define the Inhibitory Effects of Liver X Receptors and PPARG on Cancer Cell Proliferation,” Genome Medicine 8 (2016): 74, https://doi.org/10.1186/s13073‐016‐0328‐6.
B. Bandera Merchan, F. J. Tinahones, and M. Macías‐González, “Commonalities in the Association Between PPARG and Vitamin D Related With Obesity and Carcinogenesis,” PPAR Research 2016 (2016): 1–15, https://doi.org/10.1155/2016/2308249.
M. Zhao, X. Li, Y. Zhang, H. Zhu, Z. Han, and Y. Kang, “PPARG Drives Molecular Networks as an Inhibitor for the Pathologic Development and Progression of Lung Adenocarcinoma,” PPAR Research 2020 (2020): 1–7, https://doi.org/10.1155/2020/6287468.
S. Shi, G. Yu, B. Huang, Y. Mi, Y. Kang, and J. P. Simon, “PPARG Could Work as a Valid Therapeutic Strategy for the Treatment of Lung Squamous Cell Carcinoma,” PPAR Research 2020 (2020): 1–9, https://doi.org/10.1155/2020/2510951.
M. A. Ortega, L. Pekarek, F. Navarro, et al., “Updated Views in Targeted Therapy in the Patient With Non‐Small Cell Lung Cancer,” Journal of Personalized Medicine 13 (2023): 167, https://doi.org/10.3390/jpm13020167.
M. A. Ortega, F. Navarro, L. Pekarek, et al., “Exploring Histopathological and Serum Biomarkers in Lung Adenocarcinoma: Clinical Applications and Translational Opportunities (Review),” International Journal of Oncology 61 (2022): 154, https://doi.org/10.3892/ijo.2022.5444.
M. A. Ortega, M. A. Álvarez‐Mon, C. García‐Montero, et al., “Microbiota‐Gut‐Brain Axis Mechanisms in the Complex Network of Bipolar Disorders: Potential Clinical Implications and Translational Opportunities,” Molecular Psychiatry 28 (2023): 2645–2673, https://doi.org/10.1038/s41380‐023‐01964‐w.