The Clinicopathological Significances Of The Embryonic Morphogen Nodal Expression In Colon Adenocarcinoma

Objective The embryonic morphogen Nodal, a member of transforminggrowth factor-β (TGF-β) superfamily, was an important regulatory factorduring embryogenesis. As a key component of the induced signal in the earlyembryo, Nodal played an important role in early vertebrate development,including the determination of front and rear axis position and thespecification of left-right asymmetry, as well as the formation of mesodermand endoderm[1-3]. In humans, Nodal expression was largely restricted toembryonic tissues, including the trophoblast and the developing mammarygland and ovary, but was generally lost or only very low expression in normaladult tissues[4-6]. In recent years, more and more study found that Nodalre-expressed in a variety of human malignancies, such as malignant melanoma,prostate cancer, breast cancer and pancreatic cancer[7-9], which was a criticalpromote factor for the tumorigenicity, invasion and metastasis of tumor cell.Now Nodal expression in colon adenocarcinoma was unclear. Themechanisms of metastasis included epithelial-mesenchymal transition(EMT),alterations in cellular adhesion and migration, which was one of the importantcharacteristics of malignant tumors. Studies have shown that this transitionwas associated with an upregulation of embryonic stem cell-associated genes. Nodal was an embryonic factor that played a critical role in promoting earlyinvasive events during development, and epithelial calcium catenin(E-cadherin) was an important protein in the EMT[10,11]. The proliferation oftumor cells can be better responsed by Ki67, the index of Ki67was highlycorrelated with the degree of malignancy, as well as the capability of invasionand metastasis and prognosis of tumor. Therefore, it has been widely used tomeasure the proliferation in a variety of tumor cells[12-14]. The purpose of thisstudy was as follows,1. Nodal expression level was detected in normal colonmucous membrane, colon adenoma and colon adenocarcinoma.2. There weredifferent expressions of Nodal in the three tissues or not, and the relationshipsbetween Nodal and their clinical pathological significance.3. Western Blotwas used to detect the expression of Nodal protein in normal colonmucous membrane and colon adenocarcinoma.Method1. Immunohistochemistry (IHC) Envision methodA search of the surgical pathology databases were conducted at theDepartment of Pathology of the Luzhou Medical College Affiliated Hospitalfrom January2012to September2012. A total number of146colon tissueswere included in this study, including23normal colon mucous membrane(tumor distal border),23colon adenoma and100colon adenocarcinoma. Allpatients were diagnosised by two pathologists of Luzhou MedicalPathology. Collected patients ’ relevant information, including age, gender, Dukes stage,differentiation, T-stage and N-stage, via admission, medical, surgical records,examination reports and the HE slices, and recorded.All these146slices for immunohistochemistry, the antibodies including Nodal,E-cadherin and Ki67.2.Western blotAll of16fresh tissues were extracted from colon adenocarcinoma patients,including tumor and normal colon mucous membrane (tumor distal border),which from Luzhou Medical College Hospital. The expression of Nodalproteins were detected by Western Blot.Result1. IHC results showed that the expressions of Nodal in colon adenocarcinomawere significantly higher than the expressions in normal mucous membraneand colon adenoma, the positive rates were43.5%in normal colonmucous membrane,65.2%in colon adenoma and97%in colonadenocarcinoma, respectively(P <0.001).2. In100cases of colon adenocarcinoma, the expressions of Nodal werepositively correlated with tumor differentiation（r=0.362，P＜0.001）, T-stage（r=0.350，P＜0.001）and Dukes stage（r=0.253，P=0.011）, as well as theexpressions of ki67（r=0.251，P=0.012）, while they were negativelycorrelated with E-cadherin expression （r=－0.264，P=0.008）.3.Western Blot results showed that the expressions of Nodal protein in colon adenocarcinoma were significantly higher than the normal mucous membranetissues, and these results were consistent with the IHC results.Conclusion1. In this study, Nodal are low expressed in the normal colonmucous membrane tissue and colon adenomas, while highly expressed incolon adenocarcinoma.2. Nodal are related to tumor differentiation, T-stage and Dukes stage,indicating that the expression of Nodal may be contributed to colonadenocarcinoma cells proliferation, invasion and metastasis.3. Using spearman correlation analysis with E-cadherin and Ki67show thatNodal may have the capability to promote cell proliferation and metastasis ofcolon adenocarcinoma.4. Detection Nodal protein suggests a potential role for it as a novel biomarkerfor clinical diagnosis, grading and staging, may also provides a referenceabout treatment options and prognosis for clinical.