Comparison of gasless transaxillary endoscopic thyroidectomy, endoscopic thyroidectomy via areola approach and conventional open thyroidectomy in patients with unilateral papillary thyroid carcinoma.

BACKGROUND: Gasless transaxillary endoscopic thyroidectomy (GTET) and endoscopic thyroidectomy via the areola approach (ETA) have emerged as minimally invasive surgical techniques for managing papillary thyroid carcinoma (PTC). This study aimed to assess the surgical efficacy of endoscopic thyroidectomy (ET) as compared to conventional open thyroidectomy (COT) in PTC patients. METHODS: Between 2020 and 2022, 571 PTC patients underwent unilateral thyroidectomy accompanied by ipsilateral central lymph node dissection. This cohort comprised 72 patients who underwent GTET, 105 ETA, and 394 COT. The analysis encompassed a comprehensive examination of patient clinicopathologic characteristics and postoperative complaints. Furthermore, the learning curve of GTET was evaluated using the cumulative summation (CUSUM) method. RESULTS: Patients in the ET group exhibited a lower mean age and a higher proportion of female individuals. Operation time in the ET group was significantly longer. No significant differences were observed in the incidence of postoperative complications among the three groups. With regard to postoperative complaints reported three months after surgery, GTET demonstrated superior alleviation of anterior chest discomfort and swallowing difficulties. Patients who underwent ET reported significantly higher cosmetic satisfaction levels. Additionally, the learning curve of GTET was 27 cases, and the operation time during the mature phase of the learning curve exhibited a significant reduction when compared to ETA. CONCLUSIONS: The findings of this study affirm the safety and feasibility of employing GTET and ETA for the surgical management of PTC. GTET presents an attractive surgical option, particularly for patients with unilateral PTC who place a premium on cosmetic outcomes.

Construction of a TP53 mutation-associated ceRNA network as prognostic biomarkers in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) continues to endanger human health worldwide. Regulatory networks of competing endogenous RNAs (ceRNAs) play important roles in HCC. TP53 is the second most often altered gene in HCC and has a significant role in regulating target genes such as miRNAs and lncRNAs. Methods: Data from patients with TP53 mutation were collected through the cBioPortal database and differential analysis was performed to screen RNAs related to TP53 mutation. The lncRNA-miRNA-mRNA relationship was predicted by the miRcode, miRDB, and TargetScan databases. The ceRNA networks were screened and visualized by Cytoscape. Core ceRNA networks were generated by differential analysis, coexpression analysis, prognostic analysis and subcellular localization. Finally, methylation, mutation, PPI, GSEA, immunity and drug sensitivity analyses of MEX3A were performed to determine the role of MEX3A in HCC. Results: We identified 1508 DEmRNAs, 85 DEmiRNAs and 931 DElncRNAs and obtained a ceRNA network including 28 lncRNAs, 4 miRNAs and 31 mRNAs. Twenty hub DERNAs in the TP53-altered-related ceRNA network were screened out by Cytoscape and the core ceRNA network (LINC00491/TCL6-hsa-miR-139-5p-MEX3A) was obtained by multiple analyses. In addition, we discovered that the methylation level of MEX3A was decreased and the mutation frequency was raised in HCC. Furthermore, elevated MEX3A expression was associated with alterations in the HCC immunological microenvironment. Conclusion: We successfully constructed a reciprocal ceRNA network, which could provide new ideas for exploring HCC mechanisms and therapeutic approaches.

Comprehensive pan-cancer analysis reveals CCDC58 as a carcinogenic factor related to immune infiltration.

CCDC58, a member of the CCDC protein family, has been primarily associated with the malignant progression of hepatocellular carcinoma (HCC) and breast cancer, with limited research conducted on its involvement in other tumor types. We aimed to assess the significance of CCDC58 in pan-cancer. We utilized the TCGA, GTEx, and UALCAN databases to perform the differential expression of CCDC58 at both mRNA and protein levels. Prognostic value was evaluated through univariate Cox regression and Kaplan-Meier methods. Mutation and methylation analyses were conducted using the cBioPortal and SMART databases. We identified genes interacting with and correlated to CCDC58 through STRING and GEPIA2, respectively. Subsequently, we performed GO and KEGG enrichment analyses. To gain insights into the functional status of CCDC58 at the single-cell level, we utilized CancerSEA. We explored the correlation between CCDC58 and immune infiltration as well as immunotherapy using the ESTIMATE package, TIMER2.0, TISIDB, TIDE, TIMSO, and TCIA. We examined the relationship between CCDC58 and tumor heterogeneity, stemness, DNA methyltransferases, and MMR genes. Lastly, we constructed a nomogram based on CCDC58 in HCC and investigated its association with drug sensitivity. CCDC58 expression was significantly upregulated and correlated with poor prognosis across various tumor types. The mutation frequency of CCDC58 was found to be increased in 25 tumors. We observed a negative correlation between CCDC58 expression and the methylation sites in the majority of tumors. CCDC58 showed negative correlations with immune and stromal scores, as well as with NK T cells, Tregs, CAFs, endothelial cells, and immunomodulators. Its value in immunotherapy was comparable to that of tumor mutational burden. CCDC58 exhibited positive correlations with tumor heterogeneity, stemness, DNA methyltransferase genes, and MMR genes. In HCC, CCDC58 was identified as an independent risk factor and demonstrated potential associations with multiple drugs. CCDC58 demonstrates significant clinical value as a prognostic marker and indicator of immune response across various tumor types. Its comprehensive analysis provides insights into its potential implications in pan-cancer research.

Pan-Cancer Analysis of Oncogenic Role of RAD54L and Experimental Validation in Hepatocellular Carcinoma.

Background: RAD54L is a prominent member of the SWI2/SNF2 protein family, primarily involved in the homologous recombination repair (HRR) process, thereby playing a pivotal role in the repair of DNA double-strand breaks (DSBs). RAD54L has been implicated in the development of numerous tumors. Consequently, we aimed to investigate the potential contribution of RAD54L in pan-cancer. Methods: Various databases and analytical tools were employed for bioinformatics analysis. Moreover, in vitro experiments were conducted to corroborate the findings from the bioinformatics analysis and delve deeper into the role of RAD54L in hepatocellular carcinoma (HCC). Results: RAD54L expression demonstrated a significant elevation in the majority of tumors, and its overexpression was strongly associated with unfavorable survival outcomes. RAD54L displayed robust correlations with the infiltration levels of various immune cells, including cancer associated fibroblasts (CAFs), endothelial cells, and myeloid-derived suppressor cells (MDSCs). Additionally, associations were observed between RAD54L and key factors such as tumor mutation burden (TMB), microsatellite instability (MSI), multiple immune checkpoints, and immune cell infiltration. Moreover, a close relationship was observed between RAD54L expression levels in HCC and clinicopathological characteristics, as well as immune cell infiltration. Experimental techniques including qRT-PCR, Western blotting, colony-forming, Cell Counting Kit-8 (CCK-8), wound-healing, and transwell assays were employed, which collectively demonstrated that RAD54L promoted the proliferation and migration of HCC cells. Conclusion: RAD54L exhibits robust expression in both pan-cancer and HCC, exerting a significant influence on the proliferation and migration of HCC cells. These findings highlight its potential as a promising biomarker for pan-cancer and a prospective target for immunotherapy.

Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma.

BACKGROUND: Cancer stem cells (CSCs) were linked to cancer aggressiveness and poor prognosis in patients with hepatocellular carcinoma (HCC). METHODS: We integrated two external HCC cohorts to develop the stem cell subtypes according to unsupervised clustering with 26 stem cell gene sets. Between the subtypes, differences in prognosis, clinical characteristics, recognized HCC subtypes, metabolic profile, immune-related features, somatic mutation, and drug sensitivity were examined. The prognostic signature was created, and validated by numerous cohorts, and used to assess the efficacy of immunotherapy and transcatheter arterial chemoembolization (TACE) treatment. The nomogram was developed based on the signature and clinical features. We further examined the function of KIF20A in HCC and proved that KIF20A had the potential to regulate the stemness of HCC cells through western blot. RESULTS: Low stem cell patterns, a good prognosis, positive clinical features, specific molecular subtypes, low metastatic characteristics, and an abundance of metabolic and immunological aspects were associated with Cluster 1, whereas Cluster 2 was the reverse. Chemotherapy and immunotherapy were more effective in Cluster 1. Cluster 1 and CTNNB1 and ALB mutation were more closely. Additionally, the prognosis, immunotherapeutic, and TACE therapy responses were all worse in the high-risk group. The nomogram could predict the survival probability of HCC patients. KIF20A was discovered to be overexpressed in HCC and was revealed to be connected to the stemness of the HepG2 cell line. CONCLUSIONS: Two stem cell subgroups with different prognoses, metabolic, and immunological characteristics in HCC patients were identified. We also created a 7-gene prognostic signature and a nomogram to estimate the survival probability. The function of KIF20A in HCC stemness was initially examined.

Identification of FEZ2 as a potential oncogene in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the common malignant tumors with high lethal rate and poor prognosis. Dysregulation of many genes have been reported to be involved in the occurrence and development of PDAC. However, as a highly conserved gene in eukaryotes, the role of Fasciculation and Elongation protein Zeta 2 (FEZ2) in pancreatic cancer progression is not clear. In this study, we identified the oncogenic effect of FEZ2 on PDAC. By mining of The Cancer Genome Atlas (TCGA) database, we found that FEZ2 was upregulated in PDAC tissues and FEZ2 expression was negatively regulated by its methylation. Moreover, high expression and low methylation of FEZ2 correlated with poor prognosis in PDAC patients. Besides, we found that FEZ2 could promote PDAC cells proliferation, migration and 5-FU resistance in vitro. Furthermore, Gene pathway enrichment analysis demonstrated a positive correlation between Wnt signaling activation and FEZ2 expression in PDAC patients. Western blot showed that FEZ2 knockdown significantly suppressed ß-catenin expression. Collectively, our finding revealed that FEZ2 functioned as a potential oncogene on PDAC progression and migration, and the expression of FEZ2 had guidance value for the treatment and chemotherapy program of PDAC patients.

Development and validation of a ferroptosis-related prognostic model in pancreatic cancer.

BACKGROUND: The purpose of this study was to identify ferroptosis-related genes (FRGs) associated with the prognosis of pancreatic cancer and to construct a prognostic model based on FRGs. METHODS: Based on pancreatic cancer data obtained from The Cancer Genome Atlas database, we established a prognostic model from 232 FRGs. A nomogram was constructed by combining the prognostic model and clinicopathological features. Gene Expression Omnibus datasets and tissue samples obtained from our center were utilized to validate the model. The relationship between risk score and immune cell infiltration was explored by CIBERSORT and TIMER. RESULTS: The prognostic model was established based on four FRGs (ENPP2, ATG4D, SLC2A1 and MAP3K5), and the risk score was demonstrated to be an independent risk factor in pancreatic cancer (HR 1.648, 95% CI 1.335-2.035, p < 0.001). Based on the median risk score, patients were divided into a high-risk group and a low-risk group. The low-risk group had a better prognosis than the high-risk group. In the high-risk group, patients treated with chemotherapy had a better prognosis. The nomogram showed that the model was the most important element. Gene set enrichment analysis identified three key pathways, namely, TGFß signaling, HIF signaling pathway and the adherens junction. The prognostic model may be associated with infiltration of immune cells such as M0 macrophages, M1 macrophages, CD4 + T cells and CD8 + T cells. CONCLUSION: The ferroptosis-related prognostic model can be employed to predict the prognosis of pancreatic cancer. Ferroptosis is an important marker, and immunotherapy may be a potential therapeutic target for pancreatic cancer.

Cancer-Specific Targeting of Taurine-Upregulated Gene 1 Enhances the Effects of Chemotherapy in Pancreatic Cancer.

Overcoming drug resistance is one of the biggest challenges in cancer chemotherapy. In this study, we examine whether targeting the long noncoding RNA taurine upregulated gene 1 (TUG1) could be an effective therapeutic approach to overcome drug resistance in pancreatic ductal adenocarcinoma (PDAC). TUG1 was expressed at significantly higher levels across 197 PDAC tissues compared with normal pancreatic tissues. Overall survival of patients with PDAC who had undergone 5-FU-based chemotherapy was shorter in high TUG1 group than in low TUG1 group. Mechanistically, TUG1 antagonized miR-376b-3p and upregulated dihydropyrimidine dehydrogenase (DPD). TUG1 depletion induced susceptibility to 5-FU in BxPC-3 and PK-9 pancreatic cell lines. Consistently, the cellular concentration of 5-FU was significantly higher under TUG1-depleted conditions. In PDAC xenograft models, intravenous treatment with a cancer-specific drug delivery system (TUG1-DDS) and 5-FU significantly suppressed PDAC tumor growth compared with 5-FU treatment alone. This novel approach using TUG1-DDS in combination with 5-FU may serve as an effective therapeutic option to attenuate DPD activity and meet appropriate 5-FU dosage requirements in targeted PDAC cells, which can reduce the systemic adverse effects of chemotherapy. SIGNIFICANCE: Targeting TUG1 coupled with a cancer-specific drug delivery system effectively modulates 5-FU catabolism in TUG1-overexpressing PDAC cells, thus contributing to a new combinatorial strategy for cancer treatment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/7/1654/F1.large.jpg.

Identification of Molecular Subtypes and a Prognostic Signature Based on Inflammation-Related Genes in Colon Adenocarcinoma.

Both tumour-infiltrating immune cells and inflammation-related genes that can mediate immune infiltration contribute to the initiation and prognosis of patients with colon cancer. In this study, we developed a method to predict the survival outcomes among colon cancer patients and direct immunotherapy and chemotherapy. We obtained patient data from The Cancer Genome Atlas (TCGA) and captured inflammation-related genes from the GeneCards database. The package "ConsensusClusterPlus" was used to generate molecular subtypes based on inflammation-related genes obtained by differential expression analysis and univariate Cox analysis. A prognostic signature including four genes (PLCG2, TIMP1, BDNF and IL13) was also constructed and was an independent prognostic factor. Cluster 2 and higher risk scores meant worse overall survival and higher expression of human leukocyte antigen and immune checkpoints. Immune cell infiltration calculated by the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumour immune dysfunction and exclusion (TIDE), and tumour stemness indices (TSIs) were also compared on the basis of inflammation-related molecular subtypes and the risk signature. In addition, analyses of stratification, somatic mutation, nomogram construction, chemotherapeutic response prediction and small-molecule drug prediction were performed based on the risk signature. We finally used qRT-PCR to detect the expression levels of four genes in colon cancer cell lines and obtained results consistent with the prediction. Our findings demonstrated a four-gene prognostic signature that could be useful for prognostication in colon cancer patients and designing personalized treatments, which could provide new versions of personalized management for these patients.