Increased DNA content in stomach fluids: diagnostic implications of a possible new gastric cancer marker
Authors: Cadoná Francine Carla , Pelosof Adriane Graicer , Sztokfisz Claudia Zitron , Bueno Adriana Passos , Carmo dos Santos Luana Batista do , Branco Gabriela Pereira , dos Santos Gabriel Oliveira , Nunes Warley Abreu , Pintor Fernanda Araújo , de Abrantes Laís Lie Senda , Defelicibus Alexandre , Vaz Coelho Luiz Gonzaga , Leja Marcis , Fernandez Coimbra Felipe José , Drummond Rodrigo D. , da Silva Israel Tojal , Bartelli Thais F. , Nunes Diana Noronha , Dias-Neto Emmanuel 
Published: February 2023

Objective

To investigate the diagnostic and prognostic role of gastric fluid DNA (gfDNA) in gasric cancer (GC) patients and controls submitted to upper digestive endoscopy.

Design

The concentration of gfDNA was evaluated in 941 samples, including subjects with normal gastric mucosa (n = 10), peptic diseases (n = 596), pre-neoplastic conditions (n = 99), and cancer (n = 236). gfDNA levels were evaluated according to age, gender, BMI, gastric fluid’s pH, use of proton-pump inhibitors, GC tumor subtypes, histological grades, clinical stages, and disease progression/outcome.

Results

In the non-cancer group, we observed that gfDNA levels are increased in women as compared to men (p=7.44e-4). Remarkably, gfDNA levels are increased in GC patients as compared to non-GC (normal + peptic diseases, p=5.67e-13) and in GC versus pre-neoplastic disease (p=1.53e-6). Similar differences were also seen when more advanced tumors (T3) were compared to early stages (T2 and below) (p=5.97-4). Moreover, our results suggest the prognostic value of gfDNA as GC-patients with higher gfDNA concentrations (<1.28ng/µl) had increased infiltration of immune cells in the tumor (p=1.06e-3), which parallels with better disease-free survival (p= 0.014).

Conclusion

These findings highlight the significance of collecting and studying stomach fluids from gastric cancer patients and reveals the potential impact of this approach as well as its diagnostic and prognostic value for disease management.

What is already known on this topic

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The DNA contained in biofluids that are in direct contact with tumor lesions is a valuable source of information for cancer diagnosis treatment.

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Gastric fluids are in direct contact with gastric cancer (GC) lesions and immune cell infiltrates and may be a reliable source of biomarkers with multiple applications.

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Liquid biopsies are usually based on the detection and analysis of cell-free DNA found in the plasma, urine or saliva.

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Studies of the DNA present in the gastric fluids of patients (gfDNA), collected during routine endoscopy, are scarce and limited to assessing mutation profiles. It’s diagnostic and prognostic potential has not been studied so far.

What this study adds

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An analysis of gfDNA concentrations in 941 samples revealed increased DNA levels in GC patients as compared to non-GC individuals.

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When tumor stages were compared, gfDNA levels are elevated in more advanced disease.

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For GC subjects, increased gfDNA was positively associated with immune cell infiltrates and reduced tumor recurrence, suggesting this to be an informative and very low-cost prognostic marker.

How this study might affect research, practice or policy

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gfDNA collected during routine upper digestive diagnostic endoscopy can be used as an additional and very simple biomarker useful during patient follow-up and to determine cancer prognosis.

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In the future gfDNA assessment has the potential to contribute to a range of applications, such as monitoring treatment response, indicating immune cell infiltration and may potentially indicate cases with progressive disease non-responsive to chemotherapy.