Differential Expression of Cytochrome C Oxidase Subunit I Along the Colorectal Adenoma: Carcinoma Progression

Abstract

Loss in apoptosis competence often results in augmented genomic instability contributing to carcinogenesis. Cytochrome c oxidase subunit I (CcOI) can help assess apoptosis resistance in paraffin-embedded biopsies. In total, 50 colorectal cases including 10 control cases of colectomy for non-neoplastic condition, 15 cases of adenomatous colorectal polyps, and 25 cases of colorectal carcinoma were investigated in this retrospective study for immunohistochemical expression of CcOI. The staining pattern of CcOI was assessed and indices of aberrant expression were calculated as crypt-restricted loss and overall decreased immunostaining (ODI). ODI calculated in the adenocarcinoma tumor tissue was designated as Tr ODI. The crypt-restricted loss and ODI indices of the aberrant CcOI expression are significantly higher in the adenomatous polyps group (2.5% and 47.54%) and in the non-neoplastic mucosa among adenocarcinoma group (2.78% and 49.1%) when they are compared with the control group (0.55% and 7.32%) (P<0.001). A highly significant correlation was noted between Tr ODI and the tumor grade, the nodal status, and the stage among adenocarcinomas. In conclusion, colonic tumors arise in a field of crypts with aberrations in CcOI expression. This aberration is linked to biologically aggressive tumors. CcOI immunostaining may be applied on mucosal samples from patients with colonic adenomatous polyps and patients with previous cancer colon resection to determine individuals who are in need for frequent colonoscopies and/or chemopreventive strategies. Future follow-up studies are warranted to determine the level of expression predictive of recurrence or progression.

<p>Cytochrome C Oxidase Assembly Factor 1 Homolog Predicts Poor Prognosis and Promotes Cell Proliferation in Colorectal Cancer by Regulating PI3K/AKT Signaling</p>

“…22 CRC arises in a field of crypts with abnormal expression of COX1. 23 This evidence suggests that COA1 may play an important role in CRC. The present study suggested that COA1 expression in CRC was significantly associated with pathological differentiation, tumor size, and tumor depth.…”

COX5B-Mediated Bioenergetic Alterations Modulate Cell Growth and Anticancer Drug Susceptibility by Orchestrating Claudin-2 Expression in Colorectal Cancers

“…Six of these ten nuclear-encoded subunits can be replaced by isoforms, leading to heterogeneity in the composition and activity of this large complex [ 19 ]. Recently, defects or irregular expression of subunits in COX have been associated with tumorigenesis or progression in several types of cancers, including hepatocellular carcinoma (HCC), glioma, breast cancer, and CRCs [ 20 , 21 , 22 , 23 ]. However, the roles of the subunits are unclear; some are oncogenic, whereas others are suppressive in these cancers.…”

COX5B-Mediated Bioenergetic Alteration Regulates Tumor Growth and Migration by Modulating AMPK-UHMK1-ERK Cascade in Hepatoma

“…It has been demonstrated that in the macrocomplex, six of these nuclear-encoded subunits could be replaced by isoforms to retain full enzymatic activity, suggesting marked heterogeneity in the composition of this large complex and activity (for a review, see reference [16]). Recently, defects or aberrant expressions of subunits in COX have been associated with clinical prognosis in several types of cancers, including colorectal cancer, glioma, breast and hepatoma [17][18][19][20][21]. However, the actual growth regulatory roles of these subunits have not been clearly investigated.…”