Integrative Biomarker Panel for Improved Lung Cancer Diagnosis Using Plasma MicroRNAs and Sputum Bacterial DNA

Overview

Journal Curr Oncol

Publisher MDPI

Specialty Oncology

Date 2024 Oct 25

PMID 39451748

Authors

Pushpa Dhilipkannah

Ashutosh Sachdeva

Van K Holden

Feng Jiang

Affiliations

Soon will be listed here.

Abstract

This study aimed to evaluate if integrating diverse molecular biomarkers in plasma and sputum could improve the diagnosis of lung cancer. The study analyzed miRNAs in plasma and bacterial DNA in sputum from 58 lung cancer patients and 62 cancer-free smokers using droplet digital PCR. The individual plasma miRNA and sputum bacterial biomarkers had sensitivities of 62-71% and specificities of 61-79% for diagnosing lung cancer. A panel of plasma miRNA or sputum bacterial biomarkers produced sensitivities of 79-85% and specificities of 74-82%. An integromic signature consisting of two miRNAs in plasma and three bacterial biomarkers in sputum had a higher sensitivity (87%) and specificity (89%) compared to individual biomarkers. The signature's diagnostic value was confirmed in a validation cohort of 56 lung cancer patients and 59 controls, independent of tumor stage, histological type, and demographic factors. Integrating diverse molecular biomarkers in plasma and sputum could improve the diagnosis of lung cancer.

References

Marcus P . Lung cancer screening with low dose computed tomography (LDCT): looking back and moving forward. Ann Transl Med. 2015; 3(Suppl 1):S41. PMC: 4437966. DOI: 10.3978/j.issn.2305-5839.2015.03.36. View

Zhou H, Liao J, Leng Q, Chinthalapally M, Dhilipkannah P, Jiang F . Circulating Bacterial DNA as Plasma Biomarkers for Lung Cancer Early Detection. Microorganisms. 2023; 11(3). PMC: 10058358. DOI: 10.3390/microorganisms11030582. View

Li R, Todd N, Qiu Q, Fan T, Zhao R, Rodgers W . Genetic deletions in sputum as diagnostic markers for early detection of stage I non-small cell lung cancer. Clin Cancer Res. 2007; 13(2 Pt 1):482-7. DOI: 10.1158/1078-0432.CCR-06-1593. View

Hu X, Peng Q, Zhu J, Shen Y, Lin K, Shen Y . Identification of miR-210 and combination biomarkers as useful agents in early screening non-small cell lung cancer. Gene. 2019; 729:144225. DOI: 10.1016/j.gene.2019.144225. View

Braga E, Fridman M, Burdennyy A, Loginov V, Dmitriev A, Pronina I . Various LncRNA Mechanisms in Gene Regulation Involving miRNAs or RNA-Binding Proteins in Non-Small-Cell Lung Cancer: Main Signaling Pathways and Networks. Int J Mol Sci. 2023; 24(17). PMC: 10487663. DOI: 10.3390/ijms241713617. View

Chen Q, Xie X . Association of Exosomal miR-210 with Signaling Pathways Implicated in Lung Cancer. Genes (Basel). 2021; 12(8). PMC: 8392066. DOI: 10.3390/genes12081248. View

Wang X, Liu H, Shen Y, Li W, Chen Y, Wang H . Low-dose computed tomography (LDCT) versus other cancer screenings in early diagnosis of lung cancer: A meta-analysis. Medicine (Baltimore). 2018; 97(27):e11233. PMC: 6076107. DOI: 10.1097/MD.0000000000011233. View

Zheng W, Zhou Y, Lu J, Xu H, Lei L, Chen C . The prognostic value of miR-126 expression in non-small-cell lung cancer: a meta-analysis. Cancer Cell Int. 2017; 17:71. PMC: 5513344. DOI: 10.1186/s12935-017-0440-8. View

Zhang Z, Wang J, Cheng J, Yu X . Effects of miR-126 on the STAT3 signaling pathway and the regulation of malignant behavior in lung cancer cells. Oncol Lett. 2018; 15(6):8412-8416. PMC: 5950602. DOI: 10.3892/ol.2018.8360. View

10.

Hajipour S, Hosseini S, Irani S, Tavallaie M . Identification of novel potential drugs and miRNAs biomarkers in lung cancer based on gene co-expression network analysis. Genomics Inform. 2023; 21(3):e38. PMC: 10584645. DOI: 10.5808/gi.23039. View

11.

Eilertsen M, Andersen S, Al-Saad S, Richardsen E, Stenvold H, Hald S . Positive prognostic impact of miR-210 in non-small cell lung cancer. Lung Cancer. 2013; 83(2):272-8. DOI: 10.1016/j.lungcan.2013.11.005. View

12.

Aberle D, Adams A, Berg C, Black W, Clapp J, Fagerstrom R . Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011; 365(5):395-409. PMC: 4356534. DOI: 10.1056/NEJMoa1102873. View

13.

Ma J, Mannoor K, Gao L, Tan A, Guarnera M, Zhan M . Characterization of microRNA transcriptome in lung cancer by next-generation deep sequencing. Mol Oncol. 2014; 8(7):1208-19. PMC: 4198444. DOI: 10.1016/j.molonc.2014.03.019. View

14.

Mao Q, Jiang F, Yin R, Wang J, Xia W, Dong G . Interplay between the lung microbiome and lung cancer. Cancer Lett. 2017; 415:40-48. DOI: 10.1016/j.canlet.2017.11.036. View

15.

Huang B, Wu G, Peng C, Peng X, Huang M, Ding J . miR-126 regulates the proliferation, migration, invasion, and apoptosis of non-small lung cancer cells via AKT2/HK2 axis. IUBMB Life. 2021; 75(3):186-195. DOI: 10.1002/iub.2531. View

16.

Leng Q, Holden V, Deepak J, Todd N, Jiang F . Microbiota Biomarkers for Lung Cancer. Diagnostics (Basel). 2021; 11(3). PMC: 7997424. DOI: 10.3390/diagnostics11030407. View

17.

Garrett W . Cancer and the microbiota. Science. 2015; 348(6230):80-6. PMC: 5535753. DOI: 10.1126/science.aaa4972. View

18.

Fan J, Xu G, Chang Z, Zhu L, Yao J . miR-210 transferred by lung cancer cell-derived exosomes may act as proangiogenic factor in cancer-associated fibroblasts by modulating JAK2/STAT3 pathway. Clin Sci (Lond). 2020; 134(7):807-825. DOI: 10.1042/CS20200039. View

19.

Glyn T, Purcell R . Circulating Bacterial DNA: A New Paradigm for Cancer Diagnostics. Front Med (Lausanne). 2022; 9:831096. PMC: 9013860. DOI: 10.3389/fmed.2022.831096. View

20.

Pelosi G, Sonzogni A, Veronesi G, De Camilli E, Maisonneuve P, Spaggiari L . Pathologic and molecular features of screening low-dose computed tomography (LDCT)-detected lung cancer: a baseline and 2-year repeat study. Lung Cancer. 2008; 62(2):202-14. DOI: 10.1016/j.lungcan.2008.03.012. View