Prognostic value of co-expression of STAT3, mTOR and EGFR in gastric cancer

Abstract

Abstract. Signal transducer and activator of transcription 3 (Stat3), the mammalian target of rapamycin (mtOr) and epidermal growth factor receptor (EGFr), proteins that mediate intracellular signaling related to cell growth, proliferation and differentiation, have received considerable interest as possible targets for cancer treatment. We examined whether the expression of Stat3, mtOr and EGFr correlates with clinicopathological features and patient outcome in gastric cancer. tumor samples were obtained from 126 patients with gastric adenocarcinomas who underwent a radical gastrectomy between 1999 and 2002. the expression of phosphorylated Stat3 (p-Stat3), p-mtOr and EGFr was analyzed by immunohistochemical staining. the relations of these to clinicopathological factors and outcomes were assessed. the expression of p-Stat3 p-mtOr and EGFr positively correlated with the following variables related to tumor progression: the depth of tumor invasion (t1 vs. t2-4; p<0.001, p=0.036 and p<0.001, respectively), lymph node involvement (p=0.008, p=0.027 and p=0.007) and tumor stage (i vs. ii-iV; p<0.001, p=0.041 and p<0.001). the expression of p-STAT3 and EGFR was significantly related to distant metastasis and recurrence (p=0.001 and p=0.039), as well as significantly poorer disease-specific survival (DSS; p=0.0018 and p=0.026). the expression of p-Stat3 was a marginally non-significant prognostic factor for DSS (hazard ratio=2.0, 95% ci 0.91-4.5, p=0.082). increasing expression of p-Stat3, p-mtOr and EGFr was associated with progressively worse dSS. interactions among p-Stat3, p-mtOr and EGFr may play an important role in tumor progression and outcomes in patients with gastric cancer.

Causes and consequences of microsatellite instability in gastric carcinogenesis

“…Indeed, EGFR has been throughout investigated, although its role as prognostic factor remains controversial. In several studies the expression of EGFR was shown to be related with the survival of GC patients and associated with an adverse prognostic value [99][100][101][102] . However, recent studies found that positive EGFR expression is not prognostic of patient outcome in GC patients [103][104][105] .…”

Molecular Alterations in Epidermal Growth Factor Receptors as Potential Predictors of Invasion in Complete Hydatidiform Moles (CHM)

“…Experimental evidence also suggest EGFR amplification to result in a less favourable prognosis [33,35]. However, similar to previous reports, some of the over expressing cases of GTD have also registered negative for presence of gene amplification suggesting that there are multiple mechanisms involved in EGFR protein over expression [37] and alterations of the gene secondary to amplification may be important toward the oncogenic effect of EGFR [38,39].…”

Clinicopathologic and prognostic significance of human epidermal growth factor receptor in patients with gastric cancer: An updated meta-analysis

“…Reviewers identified 56 potential studies for full-text review and 31 studies were eliminated due to inadequate data for meta-analysis. Finally, 25 studies were included in the current meta-analysis [7, 9, 10, 19–40]. The detail of the screening process was shown in Figure 1.…”

“…The prognostic significance of EGFR expression in GC patients was controversial in different studies. High EGFR expression has been reported to be correlated with poor prognosis in patients with GC [7–8]. However, it has been reported that patients with high EGFR expression had favorable prognosis than those with low EGFR expression [9].…”