Predicting central cervical lymph node metastasis in papillary thyroid microcarcinoma using deep learning.

Background: The aim of this study is to design a deep learning (DL) model to preoperatively predict the occurrence of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: This research collected preoperative ultrasound (US) images and clinical factors of 611 PTMC patients. The clinical factors were analyzed using multivariate regression. Then, a DL model based on US images and clinical factors was developed to preoperatively predict CLNM. The model's efficacy was evaluated using the receiver operating characteristic (ROC) curve, along with accuracy, sensitivity, specificity, and the F1 score. Results: The multivariate analysis indicated an independent correlation factors including age ≥55 (OR = 0.309, p < 0.001), tumor diameter (OR = 2.551, p = 0.010), macrocalcifications (OR = 1.832, p = 0.002), and capsular invasion (OR = 1.977, p = 0.005). The suggested DL model utilized US images achieved an average area under the curve (AUC) of 0.65, slightly outperforming the model that employed traditional clinical factors (AUC = 0.64). Nevertheless, the model that incorporated both of them did not enhance prediction accuracy (AUC = 0.63). Conclusions: The suggested approach offers a reference for the treatment and supervision of PTMC. Among three models used in this study, the deep model relied generally more on image modalities than the data modality of clinic records when making the predictions.

Research insights into the chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM): their roles in various tumors.

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1-8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member's chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment.

The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer.

Although the incidence of thyroid cancer is increasing year by year, most patients, especially those with differentiated thyroid cancer, can usually be cured with surgery, radioactive iodine, and thyroid-stimulating hormone suppression. However, treatment options for patients with poorly differentiated thyroid cancers or radioiodine-refractory thyroid cancer have historically been limited. Altered energy metabolism is one of the hallmarks of cancer and a well-documented feature in thyroid cancer. In a hypoxic environment with extreme nutrient deficiencies resulting from uncontrolled growth, thyroid cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. This review summarizes past and recent advances in our understanding of the reprogramming of glucose metabolism in thyroid cancer cells, which we expect will yield new therapeutic approaches for patients with special pathological types of thyroid cancer by targeting reprogrammed glucose metabolism.

Emerging role of exosome-derived non-coding RNAs in tumor-associated angiogenesis of tumor microenvironment.

The tumor microenvironment (TME) is an intricate ecosystem that is actively involved in various stages of cancer occurrence and development. Some characteristics of tumor biological behavior, such as proliferation, migration, invasion, inhibition of apoptosis, immune escape, angiogenesis, and metabolic reprogramming, are affected by TME. Studies have shown that non-coding RNAs, especially long-chain non-coding RNAs and microRNAs in cancer-derived exosomes, facilitate intercellular communication as a mechanism for regulating angiogenesis. They stimulate tumor growth, as well as angiogenesis, metastasis, and reprogramming of the TME. Exploring the relationship between exogenous non-coding RNAs and tumor-associated endothelial cells, as well as their role in angiogenesis, clinicians will gain new insights into treatment as a result.

Prognostic value of sirtuin family members and experimental verification identify SIRT5 as diagnostic biomarkers in clear cell renal cell carcinoma.

Background: The sirtuins (SIRTs) family is a nicotinamide adenine dinucleotide (NAD+) family of dependent deacetylases, which includes SIRT1-7. This family is related to the development and progression of various tumors. However, a comprehensive analysis of the role of SIRTs in clear cell renal cell carcinoma (ccRCC) is still lacking, and there are few reports on the inhibitory role of SIRT5 in ccRCC. Methods: We used immunohistochemical analysis, and several bioinformatic databases to perform an integrated analysis of the expression and prognostic value of SIRT5 and other SIRT family members in ccRCC along with the associated immune cell infiltration. These databases include TIMER, THPA, cell culture, UALCAN, cBioPortal, WebGestalt, Metascape, DiseaseMeth, STRING database, and Cytoscape. Results: The protein expression of SIRT1, 2, 3, 6, and 7 were upregulated in ccRCC for the Human Protein Atlas database, whereas the expression of SIRT4 and SIRT5 was decreased. The expression based on tumor stage, and grade followed a similar trend. Kaplan-Meier analysis showed that high SIRT4 and SIRT5 expression was positively related to better overall survival (OS), whereas SIRT6 and SIRT7 expression was positively related to worse OS. Further, high SIRT3 expression was related to worse relapse-free survival (RFS), whereas high SIRT5 expression was related to better RFS. To explore the mechanism underlying the function of SIRTs in ccRCC, we also used several databases to perform the functional enrichment analysis and explore the relationship between infiltrating immune cells and seven SIRT family members in ccRCC. The results showed that several SIRT family members, and particularly SIRT5, are correlated with the infiltration of some important immune cells. The protein expression of SIRT5 was significantly lower in tumor tissue compared to normal tissue and was negatively related to the age of the patient ccRCC individual tumor stages, and grades. In human ccRCC samples, strong IHC staining expression of SIRT5 was displayed in adjacent normal tissue than in tumor tissues. Conclusion: SIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC.

Prognostic value and immune infiltration of the gasdermin family in lung adenocarcinoma.

Background: The GSDM family includes six members, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and PJVK (Pejvakin, DFNB59), which can induce pyroptosis, thereby regulating the tumorigenesis of various cancers. However, the clinical characteristics and role of the GSDM family in LUAD are not well understood. Methods: In this study, several important bioinformatics databases were used to integrate the analysis of the expression, prognostic value, and immune infiltration of GSDMs in LUAD. These databases include UALCAN, DiseaseMeth, GEPIA, THPA, cBioPortal, TIMER, WebGestalt, STRING database, and Cytoscape. Results: The findings from the UALCAN database revealed that the expression of all six GSDMs based on the tumor stage in LUAD was increased (particularly GSDMD). Our IHC results verified it. Additionally, the DiseaseMeth database showed that the methylation levels of GSDMA, GSDMB, GSDMC, and GSDMD were decreased. The expression of six GSDMs was related to shorter overall survival in patients with LUAD, according to the GEPIA database. The cBioPortal database was further used to explore the alteration rate and correlated genes in LUAD. Subsequently, these genes were subjected to functional enrichment and protein-protein interaction network analyses. We identified that the GSDM family regulate several signaling pathways, including immune-associated signaling pathways. According to tumor-infiltrating immune cell analysis from the TIMER database, GSDM family members are associated with the infiltration of important immune cells and their signature markers. Conclusions: GSDM family may be prognostic markers and novel strategies for the treatment of LUAD.

The top 100 most-cited papers in pheochromocytomas and paragangliomas: A bibliometric study.

Background: The purpose of this study was to define and analyze the characteristics of the top 100 most-cited articles and reviews on the topic of pheochromocytomas and paragangliomas (PPGLs) by using bibliometric methods. Methods: We explored the Web of Science Core Collection database to gather the 100 top-cited original articles and reviews of PPGL from 1985 to 20 December 2020. We conducted a bibliometric study to identify the most influential journals, authors, countries, and institutions in the PPGL field. Results: The 100 top-cited papers were cited a total number of 25,723 times, ranging from 131 to 1,144 (mean, 257.23 ± 173.64). All of these 100 top-cited papers were published between 1999 and 2017, and the number of top-cited papers published before 2008 (1999-2008) was significantly higher than that after 2008 (2009-2017) (p = 0.043). The journal with the highest number of published papers is the Journal of Clinical Endocrinology & Metabolism (n = 23). The United States was the most productive country in this topic, which published about half of these publications (n = 51). The National Institutes of Health (NIH) had the largest number of publications (n = 17). Genes or genetics is still the hottest topic in the field of PPGLs. Conclusions: We defined and analyzed the top 100 most-cited papers in the field of PPGLs by gathering detailed information. These data provided insights into the most influential studies related to PPGL. We hoped to inspire researchers and readers in this field to improve their understanding of PPGL research trends and provide ideas for future research from unique perspectives.

Insights into the Association Between QSER1 and M2 Macrophages and Remarkable Malignancy Characteristics in Hepatocellular Carcinoma.

PURPOSE: Glutamine and serine rich 1 (QSER1), as a DNA methylation modulator, play a crucial role in transforming tumor cells. Previous studies have shown that QSER1 plays a role in regulating the progression of various malignancies and that QSER1 dysfunction is connected with precancerous lesions of hepatocellular carcinoma (HCC) as well as HCC prognosis. However, little is known about the detailed contribution of QSER1 in HCC. PATIENTS AND METHODS: Various statistical methods such as Kaplan-Meier method, AUC analysis, GSEA, and immune-infiltration analysis were used to evaluate the relationship between QSER1 expression and clinical features, prognostic factors, and potential functional mechanisms of QSER1. RESULTS: QSER1 expression was negatively correlated with clinicopathological features (clinical stage, pathological grade, TP53 mutation, lymph node metastasis) and clinical outcome (overall survival versus recurrence). Functional enrichment analysis further suggested that QSER1 is involved in multiple pathways related to DNA replication and tumor immunity. TIMER analysis indicated that high QSER1 expression was significantly associated with higher macrophage infiltration and poorer macrophage-related outcomes. In particular, QSER1 was significantly more associated with M2 macrophages than M1 macrophages. CONCLUSION: Overall, elevated QSER1 is a potential prognostic marker for HCC and is associated with immune infiltration in HCC.

Methylation-Driven Gene PLAU as a Potential Prognostic Marker for Differential Thyroid Carcinoma.

Purpose: Aberrant DNA methylation plays a crucial role in the tumorigenesis of differentiated thyroid cancer (DTC); nevertheless, the factors leading to the local and regional recurrence of DTC are not well understood. This study aimed to establish the connection between DNA methylation-driven genes and the recurrence of DTC. Methods: RNA sequencing profiles and DNA methylation profiles of DTC were downloaded from The Cancer Genome Atlas (TCGA) database. Combined application of the methylmix R package and univariate Cox regression analyses were used to screen and distinguish prognosis-related methylation-driven genes. Multivariate Cox regression analyses were utilized to identify the target genes that were closely associated with the recurrence of DTC. Then, correlations between the expression levels of the target genes and the clinicopathological features were verified, as well as their potential biological functions. Results: A total of 168 Methylation-driven genes were differentially expressed in thyroid cancer, among which 10 genes (GSTO2, GSTM5, GSTM1, GPX7, FGF2, LIF, PLAU, BCL10, SHARPIN and TNFRSF1A) were identified as Hub genes. We selected PLAU for further analysis because PLAU was most strongly correlated with DTC recurrence and the DNA methylation levels of PLAU were closely associated with multiple clinicopathological features of DTC. PLAU was significantly upregulated in DTC, and patients with a high expression level of PLAU had a higher risk of recurrence (p < 0.05). Functional predictions suggested that PLAU-related genes were mainly involved in the regulation of immune-related signaling pathways. Moreover, the mRNA level of PLAU was found to be positively correlated with the cell markers of neutrophils and dendritic cells. In addition, we found that two DNA methylation sites (cg06829584, cg19399285) were associated with abnormal expression of PLAU in DTC. Conclusion: The methylation-driven gene PLAU is an independent risk factor for the recurrence of DTC and it functions as an oncogene through the regulation of immune-related signaling pathways, which offers new insight into the molecular mechanisms of thyroid cancer and provides new possibilities for individualized treatment of thyroid cancer patients.

Comprehensive analysis of the effect of Hashimoto's thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in papillary thyroid cancer.

Purpose: Hashimoto's thyroiditis often leads to reactive hyperplasia of the central compartment lymph nodes in papillary thyroid carcinoma (PTC) patients. However, the effect and clinical significance of Hashimoto's thyroiditis (HT) on ultrasonography evaluation for cervical lymph node (LN) lesions remain unknown. This study aims to investigate the effect of Hashimoto's thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in PTC patients. Patients and methods: This study consecutively enrolled 1,874 PTC patients who underwent total thyroidectomy and radical cervical lymph node dissection between January 2010 and December 2021. Eligible patients were categorized as with HT and without HT. The diagnostic performance of preoperative ultrasonography for cervical LN lesions (including central LNs and lateral LNs) was evaluated between PTC patients with HT and those without HT, respectively. Results: Among the 1,874 PTC patients, 790 (42.1%) had central cN+ and 1,610 (85.9%) had lateral cN+. Compared with PTC patients without HT, the preoperative US for central LNs displays a higher false-positive rate (27.9% vs. 12.2%, p <0.001) and a lower specificity (72.1% vs. 87.8%, p < 0.001) in PTC patients with HT. Moreover, in PTC patients with HT, the ratio of the absence of fatty hilum in central LNs without metastasis was higher than in PTC patients without HT (13.02% vs. 7.46%, p = 0.013). However, no such differences were observed in lateral LNs. Conclusion: HT will interfere with the preoperative US evaluation for central LNs and increase the incidence of the absence of fatty hilum in central benign LNs. When PTC patients have concomitant HT, clinicians should thoroughly evaluate the central LNs, thereby decreasing the incidence of misdiagnosis and unnecessary surgery.