Salivary Microbiome Dysbiosis is associated with Non-Smoking Male Lung Cancer and correlated with Immunocytochemistry Markers

Authors

  • Atiq Ur Rehman Department of Pulmonology, Combined Military Hospital, Peshawar - Pakistan
  • Farzeen Khan Department of Community and Preventive Dentistry, Peshawar Dental College, Peshawar, Riphah International University, Islamabad - Pakistan
  • Karishma Ali Department of Pathology, Peshawar Medical and Dental College, Riphah International University, Islamabad - Pakistan
  • Shazia Naz Department of Pathology, Kabir Medical College, Gandara University, Peshawar - Pakistan
  • Saman Hussain Department of Pathology, Northwest School of Medicine, Peshawar - Pakistan
  • Shaista Alam Department of Pathology, Pak International Medical College, Peshawar - Pakistan

Keywords:

Lung Cancer, Salivary Microbiome, Dysbiosis, Biomarker

Abstract

Background: There may be a link between oral micro-biota and a higher risk of cancer of lung, according to many researches. However, there has not been much research done on the possible link between male nonsmokers' salivary microbiota and lung cancer. Furthermore, there is a paucity of research on the connection between immunohistochemical markers and the salivary microbiota. Objective: To find an association between lung cancer and salivary microbiome in non-smoker males as well as a relationship between immunohistochemical markers and salivary microbiota. Methodology: This study was conducted at the Pulmonology Department, Combined Miitary Hospital, Peshawar Pakistan for duration of six months from January 2021 to June 2021.  A 16S rRNA gene amplicon sequencing was used to evaluate the salivary flora of 120 non-smoker male lung cancer patients and 80 healthy persons. Furthermore, we found a correlation coefficient among the salivary micro-biota and three immunohistochemistry markers likeTTF-1, Napsin A, and CK7 using Spearman's rank. Results: The lung cancer patients exhibited considerably lower microbial richness and diversity compared to the control group (p < 0.0001). The comparison of the similarity analysis between the control group and lung cancer patients showed clear changes in the composition of their flora. (p=0.001). Notably, non-smoking lung cancer male patients had comparatively greater levels of the genera of bacterial "Sphingomonas" (P < 0.05) and "Blastomonas" (p = 0.0001), while the control group had higher levels of the genus "Acinetobacter" (p = 0.001) and "Streptococcus" (P = 0.01). Conclusion: The study demonstrated that salivary flora might be a useful resource for identifying non-invasive lung cancer biomarkers. The study additionally identified distinct salivary microbiome patterns in male lung cancer patients who do not smoke. It proposed potential connections between the immune-cyto-chemistry markers and salivary microbiota used in clinical diagnostics.

Author Biographies

Farzeen Khan, Department of Community and Preventive Dentistry, Peshawar Dental College, Peshawar, Riphah International University, Islamabad - Pakistan

   

Karishma Ali, Department of Pathology, Peshawar Medical and Dental College, Riphah International University, Islamabad - Pakistan

     

Saman Hussain, Department of Pathology, Northwest School of Medicine, Peshawar - Pakistan

   

Shaista Alam, Department of Pathology, Pak International Medical College, Peshawar - Pakistan

     

References

Cho JY. Lung cancer biomarkers. Adv Clin Chem. 2015;72:107–70. DOI: 10.1016/bs.acc.2015.07.003

Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers–a different disease. Nat Rev Cancer. 2007;7:778–90. DOI: 10.1038/nrc2190

Kim JH, Park K, Yim SH, Choi JE, Sung JS, Park JY, et al. Genome-wide association study of lung cancer in Korean non smoking women. J Korean Med Sci. 2013;28:840–7. DOI: 10.3346/jkms.2013.28.6.840.

Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell. 2012;150:1121–34. DOI: 10.1016/j.cell.2012.08.024.

Lan Q, Hsiung CA, Matsuo K, Hong YC, Seow A, Wang Z, et al. Genome-wide association analysis identifies new lung cancer susceptibility loci in never smoking women in Asia. Nat Genet. 2012; 44:1330–5. DOI: 10.1038/ng.2456.

Chen H, Jiang W. Application of high-throughput sequencing in understanding human oral microbiome related with health and disease. Front Microbiol. 2014;5:508. DOI: 10.3389/fmicb.2014.00508.

Shoemark DK, Allen SJ. The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer’s disease. J Alzheimers Dis. 2015;43:725–38. DOI: 10.3233/JAD-141170.

Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21:895–905. DOI: 10.1038/nm.3914.

Li J, Hao C, Ren L, Xiao Y, Wang J, Qin X. Data mining of lung florain cystic fibrosis patients. PLoS One. 2016;11:e0164510. DOI: 10.1371/journal.pone.0164510.

Long J, Cai Q, Steinwandel M, Hargreaves MK, Bordenstein SR, Blot WJ, et al. Association of oral microbiome with type 2 diabetes risk. J Periodontal Res. 2017;52:636–43. DOI: 10.1111/jre.12432.

Shukla SD, Budden KF, Neal R, Hansbro PM. Microbiome effects on immunity, health and disease in the lung. Clin Transl Immunol. 2017; 6:e133. DOI: 10.1038/cti.2017.6.

Sun J. Mechanisms Underlying Host-Microbiome Interactions in Pathophysiology of Human Diseases. New York, NY: Springer Science Business Media. 2018. DOI: 10.1007/978-1-4939-7534-1.

Marsland BJ, Gollwitzer ES. Host-microorganism interactions in lung diseases. Nat Rev Immunol. 2014;14:827–35. doi: 10.1038/nri3769

Krishnan K, Chen T, Paster BJ. A practical guide to the oral microbiome and its relation to health and disease. Oral Dis. 2017;23:276–86. DOI: 10.1111/odi.12509.

Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B, Gao Z, et al. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome. 2013;1:19. DOI: 10.1186/2049-2618-1-19

Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, et al. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol. 2016;1:16031. DOI: 10.1038/nmicrobiol.2016.31.

Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, YuWH, et al. The human oral microbiome. J Bacteriol. 2010;192:5002–17. DOI: 10.1128/JB.00542-10.

Yan X, Yang M, Liu J, Gao R, Hu J, Li J, et al. Discovery and validation of potential bacterial biomarkers for lung cancer. Am J Cancer Res. 2015;5:3111–22.

Gomez A, Nelson KE. The oral microbiome of children: development, disease, and implications beyond oral health. Microb Ecol. 2017;73:492–503. DOI: 10.1007/s00248-016-0854-1.

Kumar PS. From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease. J Physiol. 2017;595:465– 76. DOI: 10.1113/JP272427.

Wu J, Peters BA, Dominianni C, Zhang Y, Pei Z, Yang L, et al. Cigarette smoking and the oral microbiome in a large study of American adults. ISME J. 2016;10:2435–46. DOI: 10.1038/ismej.2016.37.

Huber RM. Is lung cancer in never-smokers a different disease?–Back to the figures. J Thorac Oncol. 2007;2:787–8. DOI: 10.1097/JTO.0b013e318153f3c5.

Choi JR, Park SY, Noh OK, Koh YW, Kang DR. Gene mutation discovery research of non-smoking lung cancer patients due to indoor radon exposure. Ann Occup Environ Med. 2016;28:13. DOI: 10.1186/s40557-016-0095-2.

Ao MH, Zhang H, Sakowski L, Sharma R, Illei PB, Gabrielson E, et al. The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non-small cell lung cancer. Hum Pathol. 2014;45:926–34. DOI: 10.1016/j.humpath.2014.01.005.

Kawai T, Tominaga S, Hiroi S, Kameda K, Ogata S, Nakashima H, et al. Expressions of thyroid transcription factor-1, Napsin A, p40, p63, CK5/6 and Desmocollin-3 in non-small cell lung cancer, as revealed by imprint cytology using a malinol-based cell-transfer technique. Acta Cytol. 2015;59:457–64. DOI: 10.1159/000442659.

Pepe MS, Feng Z, Janes H, Bossuyt PM, Potter JD. Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. J Natl Cancer Inst. 2008;100:1432–8. DOI: 10.1093/jnci/djn326

Zhang L, Farrell JJ, Zhou H, Elashoff D, Akin D, Park NH, et al. Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology. 2010;138:949–57. DOI: 10.1053/j.gastro.2009.11.010.

Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, et al. Variations of oral floraare associated with pancreatic diseases including pancreatic cancer. Gut. 2012;61:582–8. DOI: 10.1136/gutjnl-2011-300784.

Zhao W, Wang H, Peng Y, Tian B, Peng L, Zhang DC. Delta Np63, CK5/6, TTF-1 and napsin A, a reliable panel to subtype non-small cell lung cancer in biopsy specimens. Int J Clin Exp Pathol. 2014; 7:4247–53.

Chen R, Ding Z, Zhu L, Lu S, Yu Y. Correlation of clinicopathologic features and lung squamous cell carcinoma subtypes according to the 2015 WHO classification. Eur J Surg Oncol. 2017;43:2308–14. DOI: 10.1016/j.ejso.2017.09.011.

Woese CR, Fox GE. Phylogenetic structure of the prokaryotic domain: the primary kingdoms. Proc Natl Acad Sci.1977;74:5088–90. DOI: 10.1073/pnas.74.11.5088.

Woese CR, Kandler O, Wheelis ML. Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci. 1990;87:4576–9. DOI: 10.1073/pnas.87.12.4576.

Magoc T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics. 2011;27:2957–63. DOI: 10.1093/bioinformatics/btr507.

Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high throughput community sequencing data. Nat Methods. 2010;7:335–6. DOI: 10.1038/nmeth.f.303 .

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Published

2021-12-02

How to Cite

Rehman, A. U. ., Khan, F. ., Ali, K. ., Naz, S. ., Hussain, S. ., & Alam, S. . (2021). Salivary Microbiome Dysbiosis is associated with Non-Smoking Male Lung Cancer and correlated with Immunocytochemistry Markers. Pakistan Journal of Chest Medicine, 27(4), 316–322. Retrieved from http://pjcm.net/index.php/pjcm/article/view/767

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