Lipidomic profiling of peritoneal lavage supernatant identifies PE/PA/PI-enriched recurrence biomarkers in cytology-negative gastric cancer.

BACKGROUND

Peritoneal dissemination accounts for more than 40% of recurrences after radical gastrectomy for gastric cancer. Although peritoneal lavage cytology (CY) is routinely used to detect intraperitoneal free cancer cells, peritoneal recurrence still occurs in a subset of CY-negative patients. Novel molecular biomarkers are urgently needed to identify high-risk individuals within this cohort.

METHODS

Direct flow injection quadrupole time-of-flight mass spectrometry (DFI-Q-TOF-MS) in negative ion mode was applied to profile peritoneal lavage supernatants from gastric cancer patients stratified by recurrence outcome (CY-R + vs. CY-R-). Candidate recurrence-associated features were selected by volcano plot, LASSO logistic regression, and Random Forest. PLS-DA with VIP scores was applied for stage-associated feature identification.

RESULTS

A recurrence-associated lipid signature was identified comprising phosphatidylethanolamine species (PE (34:0), PE (34:1), PE (38:1), PE O-38:5), phosphatidic acid PA (39:3), phosphatidylinositol PI (22:1), and oxidized sphingoid base SPB (18:3;O2), implicating membrane remodeling, lipid signaling pathway alterations, and oxidative stress in the peritoneal microenvironment of recurrence-prone patients.

CONCLUSION

This study presents an exploratory lipidomic characterization of peritoneal lavage supernatant in CY-negative gastric cancer, identifying hypothesis-generating candidate lipid features associated with recurrence status. Given the small recurrence group and absence of external validation, all findings should be interpreted as exploratory and require confirmation in prospective multicenter studies.