METHODS: We provide for the first time a blood-based assay for transcript
quantification of the metastasis inducer MACC1 in a prospective study of
gastric cancer patient plasma. MACC1 is a strong prognostic biomarker for
tumor progression and metastasis in a variety of solid cancers. We conducted a
study to define the diagnostic and prognostic power of MACC1 transcripts using
76 plasma samples from gastric cancer patients, either newly diagnosed with
gastric cancer, newly diagnosed with metachronous metastasis of gastric
cancer, as well as follow-up patients. Findings were controlled by using
plasma samples from 54 tumor-free volunteers. Plasma was separated, RNA was
isolated, and levels of MACC1 as well as S100A4 transcripts were determined by
quantitative RT-PCR. RESULTS: Based on the levels of circulating MACC1
transcripts in plasma we significantly discriminated tumor-free volunteers and
gastric cancer patients (P < 0.001). Levels of circulating MACC1 transcripts
were increased in gastric cancer patients of each disease stage, compared to
tumor-free volunteers: patients with tumors without metastasis (P = 0.005),
with synchronous metastasis (P = 0.002), with metachronous metastasis (P =
0.005), and patients during follow-up (P = 0.021). Sensitivity was 0.68
(95%CI: 0.45-0.85) and specificity was 0.89 (95%CI: 0.77-0.95), respectively.
Importantly, gastric cancer patients with high circulating MACC1 transcript
levels in plasma demonstrated significantly shorter survival when compared
with patients demonstrating low MACC1 levels (P = 0.0015). Furthermore,
gastric cancer patients with high circulating transcript levels of MACC1 as
well as of S100A4 in plasma demonstrated significantly shorter survival when
compared with patients demonstrating low levels of both biomarkers or with
only one biomarker elevated (P = 0.001). CONCLUSION: Levels of circulating
MACC1 transcripts in plasma of gastric cancer patients are of diagnostic value
and are prognostic for patient survival in a prospective study