Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Nov;17(4):505-517.
doi: 10.1007/s10238-016-0443-0. Epub 2016 Dec 1.

Differential Role of Wnt Signaling and Base Excision Repair Pathways in Gastric Adenocarcinoma Aggressiveness

Affiliations

Differential Role of Wnt Signaling and Base Excision Repair Pathways in Gastric Adenocarcinoma Aggressiveness

Alireza Korourian et al. Clin Exp Med. .

Abstract

Aberrant activation of Wnt and base excision repair (BER) signaling pathways are implicated in tumor progression and chemotherapy resistance in gastric adenocarcinoma. This study was conducted to clarify the role of E2F6 and RhoA, components of the Wnt signaling pathway, and SMUG1, a component of the BER pathway in gastric adenocarcinoma. Expression levels and clinicopathological significance of three biomarkers, namely E2F6, RhoA, and SMUG1, as potential signaling molecules involved in tumorigenesis and aggressive behavior, were examined using tissue microarray. Our analysis showed a relative increase in the expression of E2F6 in gastric adenocarcinoma with no lymph node metastasis (χ 2, P = 0.04 and OR, P = 0.08), while overexpression of RhoA and SMUG1 was found more often in the diffuse subtype of gastric adenocarcinoma as compared to the intestinal subtype (χ 2, P = 0.05, OR, P = 0.08 and χ 2, P = 0.001, OR, P = 0.009, respectively). Higher expression of RhoA was frequently seen in tumors with vascular invasion (χ 2, P = 0.01 and OR, P = 0.01). In addition, increased expression of SMUG1 was found more often in poorly differentiated tumors (χ 2, P = 0.01 and OR, P = 0.01). The distinct phenotype of E2F6Low/SMUG1High was more common in poorly differentiated tumors (P = 0.04) and with omental involvement (P = 0.01). The RhoAHigh/SMUG1High expression pattern was significantly more often found in diffuse subtype compared to the intestinal subtype (P = 0.001) as well as in poorly differentiated tumors (P = 0.004). The E2F6Low/SMUG1High and RhoAHigh/SMUG1High phenotypes can be considered as aggressive phenotypes of gastric adenocarcinoma. Our findings also demonstrated the synergistic effect of RhoA and SMUG1 in conferring tumor aggressiveness in diffuse subtype of gastric adenocarcinoma.

Keywords: Base excision repair; E2F6; Gastric cancer; RhoA; SMUG1; Wnt signaling pathway.

Similar articles

See all similar articles

Cited by 3 articles

References

    1. Mutat Res Rev Mutat Res. 2015 Jan-Mar;763:212-45 - PubMed
    1. Cold Spring Harb Perspect Biol. 2013 Apr 01;5(4):a012583 - PubMed
    1. EMBO Rep. 2002 Jul;3(7):695-700 - PubMed
    1. Drug Resist Updat. 2004 Apr;7(2):97-110 - PubMed
    1. FEBS Lett. 2008 Jun 18;582(14):2093-101 - PubMed

LinkOut - more resources

Feedback