Association between the overexpression of Her3 and clinical pathology and prognosis of colorectal cancer

Abstract

Background:This study aimed to investigate the association between the overexpression of human epidermal growth factor receptor-3 (Her3) and the clinicopathological parameters and survival of patients with colorectal cancer (CRC).Methods:Relevant studies on the overexpression of Her3 (measured by immunohistochemistry) and overall survival (OS) in patients with CRC were searched for in PubMed, EMBASE, and Cochrane Library. Published data were extracted and computed into odds ratios (ORs) for assessing the association of Her3 overexpression with tumor differentiation, tumor node metastasis (TNM) stage, position of colon cancer, sex, and age. Prognostic data were computed into hazard ratios (HRs) for OS.Results:Eight studies including 1716 patients with CRC were included in this meta-analysis. The results revealed a significant association between Her3 overexpression and tumor differentiation [OR = 2.38; 95% confidence interval (95% CI): 1.76–3.22; P < .001], TNM tumor stage (OR = 0.71; 95% CI: 0.53–0.96; P = .03), and position of colon cancer (OR = 1.71; 95% CI: 1.28–2.27; P < .001). While patients with Her3 overexpression demonstrated a worse tumor response (OR = 0.31; 95% CI: 0.16–0.60; P < .001) and OS after treatment with cetuximab (HR = 1.86; 95% CI: 1.24–2.79; P = .003), they demonstrated better OS after symptomatic treatment (HR = 0.65; 95% CI: 0.50–0.85; P = .002). Her3 overexpression was not associated with sex (OR = 1.03; 95% CI: 0.83–1.28; P = .79), age (OR = 0.96; 95% CI: 0.75–1.24; P = .77), colon or rectum site (OR = 0.79; 95% CI: 0.44–1.43; P = .44), and total OS (HR = 1.09; 95% CI: 0.69–1.72; P = .72).Conclusion:Her3 expression is associated with the clinical pathology and prognosis of CRC, which explains the nonefficacy of cetuximab treatment in patients with CRC.

Effect of Cetuximab-Conjugated Gold Nanoparticles on the Cytotoxicity and Phenotypic Evolution of Colorectal Cancer Cells

“…Typically, HER3, one member of EGFR family (EGFR, HER2, HER3, and HER4), plays a significant role in the formation of a heterodimer with EGFR on the surface of CRC cells, activating the intracellular signaling pathway when a ligand binds to the receptor [ 14 , 15 ]. The overexpression of HER3 in 30–80% of mCRC has been associated with the resistance to EGFR inhibitor [ 16 , 17 , 18 ].…”

Liver endothelium promotes HER3-mediated cell survival in KRAS wild-type and mutant colorectal cancer cells

“…The roles of HER3 in mediating cancer cell survival have been studied in different types of cancer such as breast, lung, and ovarian cancer 37,38 . In CRC, HER3 is expressed in ~ 75% of primary and metastatic tumors 39,40 , and HER3 overexpression is associated with poor prognoses in patients with CRC 41,42 . Because HER3 is a RTK protein with weak kinase activity and is considered as a "kinase-dead" receptor 43 , the canonical activation of HER3 in CRC and other cancer cells involves HER3 binding to its ligands and dimerizing with other proteins that have kinase activities.…”

Liver Endothelium Promotes HER3-mediated Cell Survival inKRASWild-type and Mutant Colorectal Cancer Cells

“…cBioPortal analysis of TCGA and multiple other databases showed that majority of the tumors (>94%) do not carry mutation, duplication, or other alterations in HER3. Meanwhile, HER3 overexpression occurs frequently and is associated with poor prognosis in patients with CRC 46,47 . As a result, HER3 inhibition has been proposed as a promising targeted therapy strategy in different types of cancers.…”