| Objective:To observe the changes in the levels of VEGF and CK18 during the evolution of gastric cancer,to explore their correlation with lymph node metastasis in patients with gastric cancer,and the value of their combined detection in the diagnosis of early lymph node metastasis in patients with gastric cancer.Methods:Collected from October 2020 to February 2022 in the Affiliated Hospital of Yan’an University by gastroscopic biopsy,pathologically confirmed cases of chronic atrophic gastritis,gastric mucosal intraepithelial neoplasia,and early and advanced gastric cancer diagnosed by surgical resection and pathological biopsy.A total of 242 cases were divided into chronic atrophic gastritis group,intraepithelial neoplasia group,early gastric cancer group and advanced gastric cancer group.Whole blood was collected and centrifuged to detect serum VEGF levels of patients in each group;gastric mucosal tissues of patients with gastric intraepithelial neoplasia were collected to determine the expression of CK18;early gastric cancer group and some advanced gastric cancer groups were collected from cancer tissues and surgically dissected gastric tissues.The expression of CK18 was determined in peripheral lymph node tissue.SPSS software was used for data analysis to analyze the correlation between relevant indicators and lymph node metastasis in gastric cancer,and ROC curves were drawn to compare the sensitivity and specificity of each index and the combined detection of VEGF and CK18 in predicting early gastric cancer lymph node metastasis.Results:（1）There were differences in serum VEGF levels among the four groups,and the difference was statistically significant（P<0.01）.（2）There were no differences in the mass concentration of VEGF in the blood serum of patients with early gastric cancer depending on gender and age,tumor localization,tumor size,and histological type（P>0.05）;differences in the degree of tumor differentiation among patients with early gastric cancer（P<0.05）were revealed,and the differences were statistically significant.（3）There were no differences in serum VEGF levels in patients with advanced gastric cancer among patients with different gender,age,tumor location,size,histological type,degree of differentiation and nerve involvement（P>0.05）;When the depth of invasion,TNM stage,HE lymph node metastasis,and intravascular tumor thrombus were different,the serum VEGF level was different（P<0.05）,and the difference was statistically significant.（4）CK18 expression results: CK18 immunohistochemical staining of gastric mucosa specimens from patients with gastric mucosal intraepithelial neoplasia did not show any colour,and CK18 expression was negative;cancer tissue and perigastric lymph node tissue from 3 out of 21 patients with early gastric cancer showed positive reaction after CK18 immunohistochemical staining,and the results of both patients were consistent,with a positive expression rate of 14.29%(3/ In 12 of the 31 patients with progressive gastric cancer,the cancer tissues and perigastric lymph node tissues showed positive reactions after CK18 immunohistochemical staining,and the two results were consistent,with a positive expression rate of 38.71%（12/31）.（5）Qualitative analysis of CK18 immunohistochemistry: using the IHC Profiler within the Image J software,the automated scores of the three patients in the early gastric cancer group were Low Positive（1+）;nine of the 12 cases in the progressive gastric cancer group showed Positive（2+）and three showed High positive（3+）.（6）Semi-quantitative analysis of CK18 immunohistochemistry: the average optical density（AOD）of CK18 in patients with early gastric cancer was different from that of patients with progressive gastric cancer（t=-26.54,P<0.01）,and the AOD value of patients with early gastric cancer（0.24±0.01）was smaller than that of patients with progressive gastric cancer（0.50±0.16）.（7）The level of positive expression of CK18 did not differ in patients with early gastric cancer by sex and age,different localizations,sizes and degrees of differentiation（P>0.05）.（8）The level of positive expression of CK18 did not differ among patients with advanced gastric cancer by gender and age,level of VEGF,tumor location and nerve damage（P>0.05）;it differed in tumor size,differentiation,depth of infiltration,and intravascular cancer thrombus（P<0.05）,with the difference being statistically significant.（9）Spearman’s correlation analysis showed that VEGF and CK18 were positively correlated with lymph node metastasis in gastric cancer.（10）The area under the ROC curve for VEGF,CK18,and VEGF+CK18 were 0.823,0.894 and 0.926,respectively.（11）The sensitivity and specificity of each index were VEGF（0.867,0.730）,CK18（0.733,0.892）,VEGF+CK18（0.867,0.973）,and the sensitivity and specificity reached the highest when VEGF and CK18 were combined,86.7% and 97.3%.Conclusion:（1）Expression of VEGF and CK18 levels showed a gradual increase in the process from gastric mucosal atrophy,intraepithelial neoplasia,early gastric cancer to advanced gastric cancer,indicating that VEGF levels and CK18 expression were associated with the onset and development of gastric cancer.（2）In patients with HE-stained early gastric cancer without metastasis to the lymph nodes,positive expression of CK18 was observed both in cancer tissues and in the perigastric lymph nodes simultaneously.It is speculated that immunohistochemical staining of CK18 in gastric mucosal biopsies of gastric cancer patients can help to predict lymph node micrometastasis at an early stage and to perform more accurate clinicopathological staging of gastric cancer.（3）The combined detection of VEGF and CK18 can improve the sensitivity and specificity of predicting early lymph node metastasis in gastric cancer,and it is expected to be an auxiliary method for predicting lymph node micrometastasis in gastric cancer. |
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