Integration of scRNA and bulk RNA-sequence to construct the 5-gene molecular prognostic model based on the heterogeneity of thyroid carcinoma endothelial cell

Abstract

Thyroid cancer (TC) is a kind of cancer with high heterogeneity, which leads to significant difference in prognosis. The prognostic molecular processes are not well understood. Cancer cells and tumor microenvironment (TME) cells jointly determine the heterogeneity. However, quite a little attention was paid to cells in the TME in the past years. In this study, we not only reveal that endothelial cells (ECs) are strongly associated with the progress of papillary thyroid cancer (PTC) using single-cell RNA-seq (scRNA-seq) data downloaded from Gene Expression Omnibus (GEO) and WGCNA, but also screen 5 crucial genes of ECs: CLDN5 , ABCG2 , NOTCH4 , PLAT , and TMEM47 . Furthermore, the 5-gene molecular prognostic model is constructed, which can predict how well a patient will do on PD-L1 blockade immunotherapy for TC and evaluate prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrates that PLAT is decreased in TC and the increase of PLAT can restrain the migratory capacity of TC cells. Meanwhile, in TC cells, PLAT suppresses VEGFa/VEGFR2-mediated human umbilical vascular endothelial cell (HUVEC) proliferation and tube formation. Totally, we construct the 5-gene molecular prognostic model from the perspective of EC and provide a new idea for immunotherapy of TC.

HPV, HBV, and HIV-1 Viral Integration Site Mapping: A Streamlined Workflow from NGS to Genomic Insights of Carcinogenesis

“…The median number of integration events at/near a cytoband or gene associated with carcinogenesis per sample was 2 (range, 2 to 10). Host genes adjacent to the VIS, which have been identified in the literature as oncogenes, tumor suppressor genes, or cancer-associated genes, were denoted in Table 2 by superscripted numerals [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. Taken together, the findings offer valuable insights into the intricate relationship between viral integration, chromosomal location, and genetic alterations that contribute to carcinogenesis.…”

“…3 Chromosomal region and band recognized as an HPV integration hotspot (i.e., 2q22.3, 3p14.2, 3q28, 8q24.21, 8q24.22, 13q22.1, 14q24.1, 17p11.1, 17q23.1, and 17q23.2) [ 42 ]. 4 Disrupted oncogenic, tumor suppressor, or cancer-associated gene(s) [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. 5 Nearby oncogenic, tumor suppressor, or cancer-associated gene(s) [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , ...…”

“…4 Disrupted oncogenic, tumor suppressor, or cancer-associated gene(s) [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. 5 Nearby oncogenic, tumor suppressor, or cancer-associated gene(s) [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ,…”