Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus.

Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.

Kang YY ，Li JJ ，Sun JX ，Wei JX ，Ding C ，Shi CL ，Wu G ，Li K ，Ma YF ，Sun Y ，Qiao H ... -  《-》

BCL2 and hsa-miR-181a-5p are potential biomarkers associated with papillary thyroid cancer based on bioinformatics analysis.

Zhang C ，Bo C ，Guo L ，Yu P ，Miao S ，Gu X ... -  《World Journal of Surgical Oncology》

Identification of biomarkers associated with cervical lymph node metastasis in papillary thyroid carcinoma: Evidence from an integrated bioinformatic analysis.

Zhang Z ，Zhao S ，Wang K ，Shang M ，Chen Z ，Yang H ，Chen Y ，Chen B ... -  《-》

OGDHL closely associates with tumor microenvironment and can serve as a prognostic biomarker for papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. However, due to the lack of reliable prognostic biomarkers for PTC, overtreatment has been on the rise. Therefore, our research aims to identify new and promising prognostic biomarkers and provide fresh perspectives for clinical decision making. The RNA-seq data and clinical data of PTC samples were obtained from The Cancer Genome Atlas data portal. GSE64912 and GSE83520 datasets were downloaded through the GEOquery R package. The difference in the expression of oxoglutarate dehydrogenase like (OGDHL) between PTC and normal tissues was explored by the Wilcoxon test. Kaplan-Meier (KM) and Cox regression analyses were used to further explore the prognostic value of OGDHL. The tumor microenvironments of PTC patients were explored based on ssGSEA and Tumor Immune Estimation Resource online database. Gene Set Enrichment Analysis (GSEA) was performed to explore the biological processes associated with OGDHL. The expression level of OGDHL in PTC was significantly altered compared to that in normal tissues (p < 0.05). Various biological processes associated with OGDHL were also explored through GSEA. KM analysis suggested that the low-OGDHL group had a better overall survival [OS, p = 3.49e-03, hazard ratio (HR) = 4.567]. The receiver operating characteristic curve also indicated the favorable prognostic potential of OGDHL. Moreover, OGDHL was proved to be an independent prognostic indicator in Cox analysis (p = 1.33e-02, HR = 0.152). In the analysis of the tumor microenvironment, the low-OGDHL group showed a lower immune score and stromal score, while tumor purity was higher. The expression of OGDHL was also closely correlated with the infiltration of immune cells. Our study elucidated the influence of OGDHL on the prognosis of PTC and demonstrated its potential as a novel biomarker, which would provide new insights into the prognosis monitoring and clinical decision making in PTC patients.

Mao M ，Huang RZ ，Zheng J ，Liang HQ ，Huang WH ，Liu J ，Li JH ... -  《Cancer Medicine》

TREM2 Is a Prognostic Biomarker and Correlated with an Immunosuppressive Microenvironment in Thyroid Cancer.

To identify the differentially expressed genes (DEGs) related to the immune microenvironment and elucidate the biological functions of key genes in papillary thyroid cancer (PTC) by analyzing the immune microenvironment. The relative quantities of immune and matrix components in 507 patients with PTC were calculated from the TCGA database. Analysis of differentially expressed genes in tumor samples throughout the genome, intersection of DEGs obtained from PTC patients, and genome-wide tumor samples and survival analysis were performed. Survival analysis was used for identification of prognostic factor. Immunohistochemical analysis of the TREM2 expression in PTC tissues, flow cytometry, and transwell assays were used to detect the effect of TREM2 on PTC cell proliferation, migration, and invasion. There were a total of 1242 upregulated genes with high intersection in the immune score and 124 downregulated genes with low intersection in the stromal score. A total of 1,366 genes in these DEGs may be determinants in the immune microenvironment. GO enrichment and KEGG enrichment analysis revealed that the overall function of DEGs appeared to map onto immune-related activities. Gene intersection and survival analysis showed that there were 435 DEG crosses in PTC patients and genome-wide tumor samples, only CXCL10, CD40LG, KRT14, TRAT1, and TREM2 were associated with patient prognosis, and TCGA showed that only the TREM2 expression was upregulated in PTC. TREM2 knockdown inhibited the cell cycle and cell proliferation, migration, and invasion by PTC cells. TREM2 was associated with the immunosuppressive microenvironment by via NF-κB pathway in PTC. TREM2 possibly was a potential indicator of altered TME status in PTC, and that TREM2 promoted PTC cell proliferation and cell cycle, migration, and invasion by NF-κB pathway.

Wang J ，Li Z 《-》