Association Of The Collagen Signature In The Tumor Microenvironment With Prognosis In Gastric Signet-ring Cell Carcinoma

Background:Gastric signet-ring cell carcinoma(SRCC/SIG)is a malignant tumor with poor biological characteristics and high degree of malignancy.The prognosis of patients with gastric signet-ring cell carcinoma currently depends on the traditional TNM staging.But TNM staging can’t fully meet the requirements of accurate prediction of prognosis.Collagen fiber is an important component of the tumor microenvironment(TME)of gastric cancer.Recent studies have shown that collagen fiber plays an important role in the prognosis of gastric cancer.So what are the characteristics of collagen structure in the tumor microenvironment of gastric signet ring cell carcinoma,especially those with poor biological characteristics and prognosis,and whether the changes of collagen structure in gastric signet ring cell carcinoma are related to prognosis,and whether the collagen characteristics can predict the prognosis of signet ring cell carcinoma have become urgent problems to be solved.Objective:By quantifying the collagen structural characteristics of the tumor microenvironment of gastric signet ring cell carcinoma,the Collagen Signature(CS)was constructed to study the correlation between the collagen structural changes and prognosis,and the prognosis prediction model of gastric signet ring cell carcinoma was constructed combining the collagen score and clinical pathological characteristics.Method:This study retrospectively collected 219 consecutive cohort of patients with signet ring cell carcinoma in the Nanfang Hospital,Southern Medical University from 2010 to 2016.The cohort was randomly divided into training cohort and validation cohort at 7:3.Collagen quantitative technology was used to extract the structural characteristics of collagen,and Lasso regression was used to select the variables to construct the collagen score,and a prognosis prediction model of gastric signet ring cell carcinoma was constructed combining the Collagen Signature and traditional clinicopathological characteristics.Results:After comparing collagen features of different pathological types of gastric cancer,the value of gastric signet ring cell carcinoma was significantly larger than the other two pathological types of gastric cancer in terms of collagen area,collagen quantity,collagen length,collagen width and collagen cross-linking space.Four collagen features were selected to construct the collagen score.The prognosis of the group with high collagen score was significantly worse than that of the group with low collagen score,which was correlated with the prognosis(p<0.05).A prognosis prediction model combining collagen score and traditional clinicopathological characteristics was constructed.The C-index of this new model was 0.821,and the area under the ROC curve(AUROC)was 0.867;The corresponding C-index of the traditional model is 0.718,and the AUROC is 0.796.The prediction efficiency of the new model is better than the traditional model(p<0.001).Conclusions:The Collagen Signature of gastric signet ring cell carcinoma was correlated with the prognosis of gastric signet ring cell carcinoma;A comprehensive model for predicting the prognosis of signet ring cell carcinoma of stomach,which includes Collagen Signature and traditional clinicopathological features,can better predict the prognosis of signet ring cell carcinoma patients.