Studies on molecular and immune signatures for detection of pancreatic cancer and COVID-19

Background and objectives: Etiological factors and accurate diagnostic biomarkers have remained elusive to pancreatic cancer, a disease with > 90% five-years mortality rate. The recent understanding of microbiome interaction with host organs has opened new research avenues on the potential role of microbiota in the tumor microenvironment. The objectives in Study I and II aim to investigate molecular and microbiome related biomarkers in plasma, saliva, pancreatic fluid and tissues from patient groups diagnosed with pancreatic cystic neoplasms, and their correlation with pancreatic neoplastic grade. The COVID-19 outbreak occurred in an unprecedented transmission rate which necessitate diagnostic biomarkers to manage the pandemic. The objective in Study III aims to investigate the potential use of saliva as a non-invasive approach for assessment of immune exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results: Study I shows that elevated bacterial 16S DNA copies and IL-1β levels in pancreas cysts correlate with high neoplastic grade. Analysis of the intracystic pancreas microbiome shows co-occurrence and enrichment of oral bacterial species. Bacteria DNA level in pancreas is also associated to prior exposure to invasive endoscopic procedures. Study II shows that elevated plasma and salivary antibody reactivity to oral pathogens (particularly F. nucleatum or Fap2 of F. nucleatum) is associated with intraductal papillary mucinous neoplasm (IPMN) diagnosis showing high-grade dysplasia or invasive cancer. Study III shows that salivary antibody reactivity to SARS-CoV-2 spike and capsid antigens persist up to 9 months after mild COVID-19 with a new multiplex antibody assay. Presence of specific salivary antibodies also correlates to COVID-19 like symptoms in a second undiagnosed cohort. The virus-specific IgG in saliva appears stable and tolerates temperature and detergent pre-treatments.

Conclusion: Collectively, the results indicate that oral microbes have a role in disease progression of pancreatic cystic neoplasms. Reducing the inflammatory microbiome may be a potential therapeutic strategy. The salivary antibody testing against oral pathogens holds interesting promise for early identification of high-risk pancreatic tumors. Furthermore, salivary antibody testings on a multiplex platform perform well and can support immune diagnostics of COVID-19. By combining at-home sample collection and the multiplex strategy, salivary diagnostics can be a sensitive and non-invasive alternative to conventional tests currently available.

List of scientific papers

I. Gaiser RA, Halimi A, Alkharaan H, Lu L, Davanian H, Healy K, Hugerth LW, Ateeb Z, Valente R, Fernández Moro C, Del Chiaro M, Sällberg Chen M. Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer. Gut. 2019 Dec;68(12):2186-2194.
https://doi.org/10.1136/gutjnl-2018-317458

II. Alkharaan H, Lu L, Gabarrini G, Halimi A, Ateeb Z, Sobkowiak MJ, Davanian H, Fernández Moro C, Jansson L, Del Chiaro M, Özenci V, Sällberg Chen M. Circulating and Salivary Antibodies to Fusobacterium nucleatum Are Associated With Cystic Pancreatic Neoplasm Malignancy. Front Immunol. 2020 Aug 28;11:2003.
https://doi.org/10.3389/fimmu.2020.02003

III. Alkharaan H#, Bayati S#, Hellström C, Aleman S, Olsson A, Lindahl K, Bogdanovic G, Healy K, Tsilingaridis G, Palma PD, Hober S, Månberg A, Nilsson P, Pin E*, Sällberg Chen M*. Persisting Salivary IgG against SARS-CoV-2 at 9 Months After Mild COVID-19 – A Complementary Approach to Population Surveys. #,*Both authors contributed equally. [Accepted]
https://doi.org/10.1093/infdis/jiab256