Role of MEK1 and DIAPH3 Expression in Colorectal Carcinoma

Abstract

Background: Colorectal carcinoma (CRC) is one of the serious causes of morbidity and mortality worldwide. It is characterized by activating mutations in genes encoding Receptor Tyrosine Kinases (RAS, RAF, MEK1 or MEK2) which act as driving oncogenes. DIAPH3 deficiency has been reported to enhance cancer cell motility, invasion and metastasis and also correlates with aggressive behaviour of cancer. Aim: To study the overexpression of MEK1 and DIAPH3 in CRC patients and their prognostic significance. Methods: We examined the immunohistochemical expression of MEK1 and DIAPH3 using tissue microarray technique in 150 CRC specimens divided into two groups. The mucinous group (MG) included specimens of 56 mucinous adenocarcinoma and 19 signet ring cell carcinoma, while the non-mucinous group (NMG) included 75 non-mucinous adenocarcinoma specimens for comparison. Results: MEK1 and DIAPH3 were strongly expressed in >50% of the studied specimens. The positivity of MEK1 expression was significantly higher in NMG compared to MG (66.7% and 34.3%, respectively; p<0.001). In all cases, the overexpression of MEK1 was significantly associated with peri-tumoral and intra-tumoral lymphocytic response (p=0.005 and 0.008, respectively). Furthermore, MEK1 overexpression showed statistically significant correlation with better OS (p=0.023) in the whole group of patients. The expression of DIAPH-3 did not differ significantly between NMG and MG (53.3% and 47.1%, respectively; p=0.456). There was strong relation between the overexpression of MEK1 and DIAPH3 (p<0.001). Conclusion:The results suggest a potential synergistic role of MEK1 and DIAPH3 overexpression and the development of CRC. Further large scale studies are warranted.

Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence

“…Therefore, we hypothesized that MEK1 and DIAPH3 expressions may have a significant interplay at the process of colorectal carcinogenesis. A correlated overexpression of DIAPH3 and MEK1 was previously observed in colorectal carcinoma [6]. So far as we know, the involvement of MEK1 and DIAPH3 in adenoma-carcinoma sequence has not been studied yet.…”

“…Diaphanous-related formin-3 (DIAPH3) has an important function in nucleation, elongation and bundling of linear actin filaments and regulates microtubule stability through direct interaction with microtubules [5,6]. Thus, DIAPH3 could act as regulator of metastasis through inhibiting the cells from gaining the amoeboid behavior in different types of cancers.…”