ABSTRACT
Background@#Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. @*Methods@#We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. @*Results@#Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. @*Conclusion@#The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.
ABSTRACT
Background:Cervical cancer is the third leading cause of cancer death in women of less developed countries due to poor screening and decreased diagnostic approaches. We aimed to investigate and differentiate the distinct clinicopathological characteristics and prevalence of endogenous and exogenous cervical in hospitalized patients. Methods:A study was performed contained 663 patients that were enrolled and underwent for screening of endogenous and exogenous cervical cancer in Qilu Hospital of Shandong University, from January 2010 to March 2015.Results:Our results indicated that combined examination of thin-prep liquid-based cytology test and human papillomavirus(HPV)-DNA are effective for diagnosis of endogenous and exogenous cervical cancer. The clinicopathological characteristics based on tumor growth pattern, and highrisk HPV-DNA incidence had no significant difference (p>0.05) in endogenous and exogenous cervicalcancer patients. The higher ratio of lymph node metastasis in endogenous cervical cancer and exogenous cervical cancer during IB1-stage (24.3% vs 12.9%), and in IIA2-stage (36.4% vs 25%) was observed respectively. In addition, our data provide compelling evidence that the level of deep interstitial infiltration, and lymphatic vascular infiltration in endogenous cervical cancer was collectively higher (82.7% and 33%) compared to exogenous cervical cancer (62.4% and18.3%) respectively during all stages.Conclusions:The higher percentage of lymph node metastasis,deep interstitial infiltration, and lymphatic vascular infiltration was observed in endogenous cervical cancer which might be the biomarker and differential key points for the diagnosis of endogenous cervical cancer. Taken together, our study provides clinicopathological features to diagnose, and differentiate the endogenous and exogenous type cervical cancer with its prevalence.