Analysis of the key ligand receptor CADM1_CADM1 in the regulation of thyroid cancer based on scRNA-seq and bulk RNA-seq data.

Advanced papillary thyroid cancer (PTC) has a poor prognosis, 60~70% of which become radio iodine refractory (RAI-R), but the molecular markers that assess PTC progress to advanced PTC remain unclear. Meanwhile, current targeted therapies are badly effective due to drug resistance and adverse side effects. Ligand-receptor pairs (L/R pairs) play an important role in the interactions between tumor cells and other cells in the tumor microenvironment (TME). Nowadays, therapies targeting ligand-receptor pairs in the TME are advancing rapidly in the treatment of advanced cancers. However, therapies targeting L/R pairs applied to advanced PTC remains challenging because of limited knowledge about L/R pairs in PTC. We screened the critical L/R pair: CADM1-CADM1 using 65311 single-cell RNA sequencing (scRNA-seq) samples from 7 patients in different stage of PTC and bulk RNA-seq datasets containing data from 487 tumor samples and 58 para-carcinoma samples. Moreover, the expression levels of CADM1-CADM1 was assessed by quantitative real time polymerase chain reaction (qRT-PCR) and the function was analyzed using Transwell immigration assay. We found that CADM1_CADM1 could be regarded as a biomarker representing a good prognosis of PTC. In addition, the high expression of CADM1_CADM1 can strongly increase the sensitivity of many targeted drugs, which can alleviate drug resistance. And the results of qRT-PCR showed us that the expression of CADM1_CADM1 in PTC was down-regulated and overexpression of CADM1 could suppresses tumor cell invasion migration. Our study identified that CADM1_CADM1 played an essential role in the progression of PTC for the first time and our findings provide a new potential prognostic and therapeutic ligand-receptor pair for advanced PTC.

He H ，Cong S ，Wang Y ，Ji Q ，Liu W ，Qu N ... -  《Frontiers in Endocrinology》

Integrated analysis of tumor microenvironment features to establish a diagnostic model for papillary thyroid cancer using bulk and single-cell RNA sequencing technology.

Wang Y ，Song W ，Li Y ，Liu Z ，Zhao K ，Jia L ，Wang X ，Jiang R ，Tian Y ，He X ... -  《-》

Single-cell and bulk RNA sequencing reveal heterogeneity and diagnostic markers in papillary thyroid carcinoma lymph-node metastasis.

Lu DN ，Zhang WC ，Lin YZ ，Jiang HY ，He R ，Li SL ，Zhang YN ，Shao CY ，Zheng CM ，Xu JJ ，Ge MH ... -  《-》

Receptor-ligand pair typing and prognostic risk model for papillary thyroid carcinoma based on single-cell sequencing.

The papillary thyroid carcinoma (PTC) microenvironment consists of various cancer and surrounding cells, and the communication between them is mainly performed through ligand-receptor (LR) interactions. Single-cell RNA sequencing (scRNA-seq) has been performed to investigate the role of intercellular communication networks in tumor progression. In addition, scRNA-seq can accurately identify the characteristics of immune cell subsets, which is of great significance for predicting the efficacy of immunotherapy. In this study, the cell-cell communication network was analyzed through LR pairs, and a new PTC molecular phenotype was developed based on LR pairs. Furthermore, a risk model was established to predict patient response to PD-1 blockade immunotherapy. The scRNA-seq dataset was obtained from GSE184362, and the bulk tumor RNA-seq dataset was obtained from The Cancer Genome Atlas. CellPhoneDB was used for cellular communication analysis. LR pair correlations were calculated and used to identify molecular subtypes, and the least absolute shrinkage and selection operator (Lasso) Cox regression was used to develop a risk model based on LR pairs. The IMvigor210 and GSE78220 cohorts were used as external validations for the LR.score to predict responses to PD-L1 blockade therapy. A total of 149 LR pairs with significant expression and prognostic correlation were included, and three PTC molecular subtypes were obtained from those with significant prognostic differences. Then, five LR pairs were selected to construct the risk scoring model, a reliable and independent prognostic factor in the training set, test set, and whole dataset. Furthermore, two external validation sets confirmed the predictive efficacy of the LR.score for response to PD-1 blockade therapy.

Cao ZX ，Weng X ，Huang JS ，Long X ... -  《Frontiers in Immunology》

Comprehensive transcriptome and scRNA-seq analyses uncover the expression and underlying mechanism of SYNJ2 in papillary thyroid carcinoma.

Synaptojanin 2 (SYNJ2) has crucial role in various tumors, but its role in papillary thyroid carcinoma (PTC) remains unexplored. This study first detected SYNJ2 protein expression in PTC using immunohistochemistry method and further assessed SYNJ2 mRNA expression through mRNA chip and RNA sequencing data and its association with clinical characteristics. Additionally, KEGG, GSVA, and GSEA analyses were conducted to investigate potential biological functions, while single-cell RNA sequencing data were used to explore SYNJ2's underlying mechanisms in PTC. Meanwhile, immune infiltration status in different SYNJ2 expression groups were analyzed. Besides, we investigated the immune checkpoint gene expression and implemented drug sensitivity analysis. Results indicated that SYNJ2 is highly expressed in PTC (SMD = 0.66 [95% CI: 0.17-1.15]) and could distinguish between PTC and non-PTC tissues (AUC = 0.74 [0.70-0.78]). Furthermore, the study identified 134 intersecting genes of DEGs and CEGs, mainly enriched in the angiogenesis and epithelial-mesenchymal transition (EMT) pathways. Subsequent analysis showed the above pathways were activated in PTC epithelial cells. PTC patients with high SYNJ2 expression showed higher sensitivity to the six common drugs. Summarily, SYNJ2 may promote PTC progression through angiogenesis and EMT pathways. High SYNJ2 expression is associated with better response to immunotherapy and chemotherapy.

Yang YP ，Huang ZG ，Luo JY ，He J ，Shi L ，Chen G ，Chen SY ，Deng YW ，Yang YJ ，Tang YJ ，Pang YY ... -  《-》