Predictive value of peripheral blood leukocytes-based methylation of Long non-coding RNA MALAT1 and H19 in the chemotherapy effect and prognosis of gastric cancer

Background: The predictive value of the methylation of Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and H19 promoters in peripheral blood leukocytes as a non-invasive biomarker for the chemotherapy effect and prognosis gastric cancer (GC) is unclear.

Methods: The DNA methylation of H19 and MALAT1 between chemotherapy-sensitive and non-sensitive groups and between groups with better and worse survival of GC was compared using regression analyses. Several predictive nomograms were constructed. The genetic alteration of MALAT1 and H19 and the association between gene expression and immune status in GC were also investigated using bioinformatics analysis.

Results: Higher genetic methylations in peripheral blood were noticed in GC groups with poorer survival. The constructed nomograms presented strong predictive values for the chemotherapy effect and 3-year survival of disease-free survival, progression-free survival, and overall survival, with the area under the curve as 0.838, 0.838, 0.912, and 0.925, respectively. Significant correlations between MALAT1 or H19 expression and marker genes of immune checkpoints and immune pathways were noticed. The high infiltration of macrophages in H19-high and low infiltration of CD8+ T cells in MALAT1-high groups were associated with worse survival of GC.

Conclusions: MALAT1 and H19 have the potential to predict the chemotherapy response and clinical outcomes of GC.