Altered Gene Expression of Cancer-Associated Fibroblasts is Related to Stiffness Properties between Different Tumor Architectures of Upper Tract Urinary Carcinoma

Abstract

Recent publications have assessed the prognostic significance of tumor architecture in upper tract urinary carcinoma (UTUC), including sessile architecture (SA) type and papillary architecture (PA) type. However, there are still no reports of the mechanisms about the differences of biomechanical properties and gene expression between two types. After retrospectively reviewing the medical records of UTUC who had undergone surgery at multi-centers, we detected average elasticity value and structural changes of tumor-matrix between PA type UTUC and SA type UTUC. The gene expression profiles between two types were identified by mRNA expression profiling and quantitative real-time PCR (qRT-PCR). Moreover, the expression of cancer-associated fibroblasts and extracellular matrix were detected by immunohistochemical staining.The multi-center retrospective study of 241 patients showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with SA type UTUC had significantly poor progression-free survival (PFS) and cancer specific survival (CSS). Then, we further reported that SA type has more elastic value (63.74±3.88 Kpa vs 32.46±1.68 Kpa) and higher tumor-stroma ratio (54.41±2.85 vs 29.87±1.41) than PA type. Microarray analysis of mRNA expression profiles and qRT-PCR showed that genes clustered of cancer-associated fibroblasts marker, composition of extracellular matrix (ECM) marker and epithelial mesenchymal transition (EMT) marker may be closely associated with progression and metastasis in patients with SA type UTUC.These studies may offer a useful marker for investigation tumor development, search therapeutic target and evaluation of disease prognosis for two types of UTUC. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (No. 31800787,No. 31570953,No. 31470799 and No. 81372761) and the Natural Science Foundation of Liaoning Province (No. 5061116). the Doctoral Research Startup Foundation of Liaoning Province (No. 20180540020) and the Medical Scientific Research Project of Dalian City (No. 1812038) . Declaration of Interests: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Ethics Approval Statement: approval by the institution Ethics Committee (No.LCKY2015-08)