An Epithelial-Mesenchymal Transition (EMT) Preoperative Nomogram for Prediction of Lymph Node Metastasis in Bladder Cancer (BLCA)

Abstract

Lymph node (LN) metastasis is a lethal independent risk factor for patients with bladder cancer (BLCA). Accurate evaluation of LN metastasis is of vital importance for disease staging, treatment selection, and prognosis prediction. Several histopathologic parameters are available to predict LN metastasis postoperatively. To date, medical imaging techniques have made a great contribution to preoperatively diagnosis of LN metastasis, but it also exhibits substantial false positives. Therefore, a reliable and robust method to preoperatively predict LN metastasis is urgently needed. Here, we selected 19 candidate genes related to epithelial-mesenchymal transition (EMT) across the LN metastasis samples, which was previously reported to be responsible for the subtype transition and correlation with malignancy and prognosis of BLCA, to establish an EMT-LN signature through LASSO logistic regression analysis. The EMT-LN signature could significantly predict LN metastasis with high accuracy in the TCGA-BLCA cohort, as well as several independent cohorts. As integrating with C3orf70 mutation, we developed an individualized prediction nomogram based on the EMT-LN signature. The nomogram exhibited good discrimination on LN metastasis status, with AUC of 71.7% and 75.9% in training and testing datasets of the TCGA-BLCA cohort. Moreover, the EMT-LN nomogram displayed good calibration with p > 0.05 in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis (DCA) revealed that the EMT-LN nomogram was of high potential for clinical utility. In summary, we established an EMT-LN nomogram integrating an EMT-LN signature and C3orf70 mutation status, which acted as an easy-to-use tool to facilitate preoperative prediction of LN metastasis in BLCA individuals.

A tumor microenvironment preoperative nomogram for prediction of lymph node metastasis in bladder cancer

“…Logistic regression analysis was used to determine the predictive characteristics of preoperative lymph node metastasis. Considering that the pathological staging and detailed classification of TNM are more obtained by postoperative pathological examination than preoperative evaluation, in this study we included the StrLNM signature and mutation of C3orf70, which were proved to be obviously highly mutated in LN+ tumors when compared with LNtumors (Table S6) (19), as the candidate features to build the preoperative nomogram. Logistic regression found the StrLNM signature and C3orf70 mutation were statistically significant (p < 0.05) (Table S6).…”

“…In recent decades, we have seen a shift from a single analysis of multiple biomarkers to the combinatorial analysis of a panel of biomarkers to construct markers, which is regarded as an useful and effectivetool for clinical management methods ( 18 ). Our team previously built a nomogram combining an EMT-LNM signature and somatic genetic mutations for prediction of LNM in BLCA which was pretty useful for clinical practice ( 19 ). And in the current study, we focused on TME patterns and tried to establish a nomogram which was centered on an StrLNM signature for preoperative prediction of LNM status in BLCA patients.…”

SMC1A facilitates gastric cancer cells proliferation, migration and invasion via promoting SNAIL activated EMT

“…This process was induced by several EMT associated factors, such as the epithelial marker E-cadherin, the mesenchymal markers N-cadherin and vimentin, and the group of transcriptional repressors Zeb, SNAIL, Slug and Twist [30]. Accumulated evidences have revealed that EMT participates in tumor invasion and metastasis [28,31,32]. The reducing of E-caherin expression is one of signi cant EMT hallmark, as it's the crucial epithelial marker of EMT which distributed in epithelial cells junctions and participates in the composition of intercellular adhesion complex [28].…”

SMC1A facilitates gastric cancer cells proliferation, migration and invasion via promoting SNAI2 activated EMT

“…This process was induced by several EMT associated factors, such as the epithelial marker E-cadherin, the mesenchymal markers N-cadherin and vimentin, and the group of transcriptional repressors Zeb, Snail, Slug and Twist (Cao et al, 2020b). Accumulated evidences have revealed that EMT participates in tumor invasion and metastasis (Cao et al, 2020a, Maruta and Greer, 1988, Zhou et al, 2019. The reducing of E-caherin expression is one of significant EMT hallmark, as it's the crucial epithelial marker of EMT which distrubuted in epithelial cells junctions and participates in the composition of intercellular adhesion complex (Zhou et al, 2019).…”