In-Depth Proteomic Analysis of Tissue Interstitial Fluid Reveals Biomarker Candidates Related to Varying Differentiation Statuses in Gastric Adenocarcinoma

The proteomic heterogeneity of gastric adenocarcinoma
(GC) has
been extensively investigated at the bulk tissue level, which can
only provide an average molecular state. In this study, we collected
an in-depth quantitative proteomic dataset of tissues and interstitial
fluids (ISFs) from both poorly and non-poorly differentiated GC and
presented a comprehensive analysis from several perspectives. Comparison
of proteomes between ISFs and tissues revealed that ISF exhibited
higher abundances of proteins associated with blood microparticles,
protein–lipid complexes, immunoglobulin complexes, and high-density
lipoprotein particles. Also, consistent and inconsistent protein abundance
changes between them were revealed by a correlation analysis. Interestingly,
a more pronounced difference between tumors and normal adjacent tissues
was found at the ISF level, which accurately reflected tissue properties
compared to those of bulk tissue. Two ISF-derived biomarker candidates,
calsyntenin-1 (CLSTN1) and prosaposin (PSAP), were identified by distinguishing
patients with different differentiation statuses and were further
validated in serum samples. Additionally, the silencing of CLSTN1
and PSAP was demonstrated to suppress cell proliferation, migration,
and invasion in poorly differentiated gastric cancer cell lines. In
summary, the ISF proteome offers a new perspective on tumor biology.
This study provides a valuable resource that significantly enhances
the understanding of GC and may ultimately benefit clinical practice.