The main treatment of esophageal cancer is surgical resection, but it is very difficult to treat those who relapse or progress. Therefore, it is of great significance to study the potential biomarkers of ESCC, reveal its potential mechanism, and find a potential effective targeted drug to improve the prognosis of ESCC patients. In recent years, a large number of studies have suggested that Wnt/β-cantenin signaling pathway plays an important role in the occurrence and development of esophageal cancer, so we aimed to find out the role of its key proteins.
Wnt2/β-cantenin signaling pathway plays an important role in regulating the growth and differentiation of cell cycle during the growth and differentiation of tissue and embryo, and also plays an important role in the development of many malignant tumors, such as esophageal cancer , breast cancer , cervical cancer . Wnt2, β-cantenin, GSK3β and Survivin are key proteins of Wnt pathway, which play an important role in regulating cell proliferation, inhibiting cell differentiation and cell cycle.
In this study, we found that there is a certain relationship between the age of ESCC patients and ethnic groups. The proportion of Kazak patients under 60 years old is higher than that of Han nationality, suggesting that Kazak patients with esophageal cancer are younger, Kazak patients with esophageal cancer lymph node metastasis rate is lower than that of Han nationality, suggesting that Kazak patients with esophageal cancer are less likely to have metastasis than that of Han nationality, considering their own living habits and personal body Physical quality. However, there was no significant difference in total and progression free survival between 112 Kazak and 114 Han ESCC patients.
As a carcinogen, Wnt2 can be detected to increase expression in many cancers and participate in tumor progression. It has also been found that Wnt2 can promote the growth of NSCLC cells by activating Wnt/β-cantenin signaling pathway. In human colorectal cancer (CRC), Wnt2 selectively increases in cancer-related fibroblasts (CAF), leading to increased invasion and metastasis. It is mainly associated with the expression of Wnt2, which leads to the increase of angiogenesis, vascular density and tumor volume. In rectal cancer, Wnt2 is associated with tumor invasion depth, lymph node metastasis, TNM stage, vascular invasion and recurrence. We found that Wnt2 was highly expressed in esophageal cancer, and it was related to TNM stage and lymph node metastasis. High TNM stage or lymph node metastasis was the positive rate of Wnt2, so it was considered that Wnt2 could promote the development of ESCC.
Survivin is a member of the inhibitor apoptosis gene family. The gene may be related to the aggressive behavior in many types of cancer, such as ovarian , bladder cancer , esophageal ,  and so on. In our study, we found that the high expression of survivin was related to the depth of invasion, and the positive expression of Survivin in patients with esophageal cancer invading into the muscular layer and the whole layer was higher than that in patients only invading into the mucosal layer, suggesting that survivin can be used as a predictor of invasion progress. Moreover, we found that survivin is related to the progression free survival of esophageal cancer patients. The progression free survival of patients with positive survivin expression is shorter than that of patients with negative survivin expression. Therefore, we consider survivin as an independent prognostic factor of esophageal squamous cancer patients. At the same time, it has also been found that the high expression of Survivin in ESCC is related to the degree of tissue differentiation and invasion, and the prognosis of patients with high expression of survivin ESCC is relatively poor.It is consistent with our conclusion. The expression of Wnt2 was negatively correlated with the expression of survivin. However, the actual expression rate of survival in esophageal cancer tissue is higher than that in normal mucosa tissue. The reason may be that although the expression rate is higher than that in normal tissue, it may be because the sample size is not enough to lead to the low positive rate, resulting in the phenomenon of negative correlation with Wnt2 expression.
GSK3β has been found to be a tumor suppressor gene in many tumors. FAK / Pyk2 can activate Wnt/β-cantenin signal transduction by phosphorylating GSK3β, and DAX1 can promote the growth and tumorigenicity of cervical cancer cells by phosphorylating GSK3β;mir-135a can activate Wnt/β-cantenin, signaling pathway by down regulating GSK3 β expression, thus accelerating EMT of bladder cancer cells, promoting invasion and migration . In this study, GSK3β was found to be low expression in ESCC, and TNM stage was related, but it was not found that GSK3β had an impact on the prognosis of esophageal cancer. However, in 29 cases of ESCC, the mRNA expression of GSK3β was higher than that of normal mucosa, and the mRNA expression ofβ-cantenin, survivin and GSK3βwere correlated with each other. Considering that they were Wnt signal proteins, there was a relationship of mutual regulation.
β-cantenin, is the key protein of Wnt signaling pathway. It is reported that acly stabilizes β-cantenin, protein through interaction, promotes the transport of CTNNB1 from cytoplasm to nucleus, and then promotes the transcription activity of β-cantenin, and the migration and invasion ability of colon cancer cells . this study found that the expression of β-cantenin, in ESCC was high, which was related to the depth of invasion, radiotherapy and chemotherapy, and was related to the expression of Wnt2 at the protein level. At the transcription level, it was found that the expression of β-cantenin, mRNA was positively correlated with the expression of GSK3β. In Ishiguro Hideyuki's study, it was also found that β-cantenin, was associated with TNM stage and lymph node metastasis in esophageal cancer patients, and was co expressed with CDH1 . It is suggested that there may be a co expression relationship between β-cantenin and Wnt2, GSK3β.
In conclusion, Wnt2,β-cantenin and Survivin are highly expressed in Wnt/β-cantenin signaling pathway in ESCC. Wnt2 is related to TNM stage and lymph node metastasis. β-cantenin, is related to depth of invasion and radiotherapy and chemotherapy. Survivin is related to depth of invasion. All the above proteins promote the development of esophageal carcinoma. GSK-3 is low expression in protein level, TNM stage is related, considering that it can inhibit the development of ESCC, but there may be phosphorylation of GSK3βto promote the development of esophageal cancer. Lymph node metastasis, nerve invasion and hematogenous metastasis can be used as independent factors to affect the overall survival of patients with ESCC. The Overalll survivalof patients with lymph node metastasis, nerve invasion and hematogenous metastasis is shorter. TNM stage, lymph node metastasis, nerve invasion, radiotherapy and chemotherapy, and Survivin are all independent influence shadows of esophageal cancer patients in squamous non progression stage, which can affect the occurrence and development of esophageal cancer patients. In TNM stage, patients in stage I and stage II did not show disease progression for a longer time than those in stage III and stage IV, patients without nerve infiltration, blood metastasis and postoperative radiotherapy and chemotherapy had a longer progression free survival period, and patients with survivin positive had a shorter recurrence time than those with negative. In addition, the expression of Wnt2, β-cantenin, GSK3β and Survivin were not significantly different between Han and Kazak, and there was no significant difference in the total and progression free survival of Kazak esophageal cancer patients.