ABSTRACT
Diabetes mellitus (DM) is recognized as a risk factor for hepatocellular carcinoma (HCC). High glucose levels have been implicated in inducing epithelial-mesenchymal transition (EMT), contributing to the progression of various cancers. However, the molecular crosstalk remains unclear. This study aimed to elucidate the molecular mechanisms linking DM to HCC. Initially, the expression of NCAPD2 in HCC cells and patients was measured. A series of functional in vitro assays to examine the effects of NCAPD2 on the malignant behaviors and EMT of HCC under high glucose conditions were then conducted. Furthermore, the impacts of NCAPD2 knockdown on HCC proliferation and the ß-catenin pathway were investigated in vivo. In addition, bioinformatics methods were performed to analyze the mechanisms and pathways involving NCAPD2, as well as its association with immune infiltration and drug sensitivity. The findings indicated that NCAPD2 was overexpressed in HCC, particularly in patients with DM, and its aberrant upregulation was linked to poor prognosis. In vitro experiments demonstrated that high glucose upregulated NCAPD2 expression, enhancing proliferation, invasion, and EMT, while knockdown of NCAPD2 reversed these effects. In vivo studies suggested that NCAPD2 knockdown might suppress HCC growth via the ß-catenin pathway. Functional enrichment analysis revealed that NCAPD2 was involved in cell cycle regulation and primarily interacted with NCAPG, SMC4, and NCAPH. Additionally, NCAPD2 was positively correlated with EMT and the Wnt/ß-catenin pathway, whereas knockdown of NCAPD2 inhibited the Wnt/ß-catenin pathway. Moreover, NCAPD2 expression was significantly associated with immune cell infiltration, immune checkpoints, and drugs sensitivity. In conclusion, our study identified NCAPD2 as a novel oncogene in HCC and as a potential therapeutic target for HCC patients with DM.
ABSTRACT
Background: Hepatocellular carcinoma (HCC) is the deadliest malignancy. Long non-coding RNAs (lncRNAs) are involved in the development of multiple human malignancies. This study aimed to establish a reliable signature and identify novel biomarkers for HCC patients. Methods: Differentially expressed lncRNAs (DElncRNAs) were identified from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate, LASSO, and multivariate Cox regression analyses were applied to screen the prognostic lncRNAs and establish a prognostic model. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were conducted to validate the prognostic value of this model. The association between lncRNAs and differential m6A genes was analyzed by Spearman's analysis. A series of bioinformatic and in vitro experiments were applied to explore the function of hub lncRNA. Results: A total of 32 DElncRNAs were identified, and 12 DElncRNAs were associated with the prognosis of HCC patients. A prognostic signature comprising six prognostic lncRNAs (LINC02428, LINC02163, AC008549.1, AC115619.1, CASC9, and LINC02362) was constructed, and the model exhibited an excellent capacity for prognosis prediction. Furthermore, 12 differential m6A regulators were identified, and RBMX was found to be correlated negatively with the hub lncRNA AC115619.1. The expression level of AC115619.1 was lower in HCC tissues than that in normal tissues and was significantly related to clinicopathologic features, survival rate, and drug sensitivity. Overexpression of AC115619.1 notably inhibited the proliferation, migration, and invasion of HCC cells. Conclusion: This study provided a promising prognostic signature for HCC patients and identified AC115619.1 as a novel biomarker, which plays an essential role in regulating the progression of HCC.
ABSTRACT
Background: As the prevalence of Hashimoto's thyroiditis (HT) and thyroid cancer (TC) has been increasing dramatically in recent years, the association between the two diseases has been widely debated and studied. However, no consistent findings are available and the relationship remains controversial. In this study, we analyzed the influence of HT on the diagnosis and treatment of thyroid nodules and investigated the relationship between HT and TC. Methods: From Jan 2017 to Apr 2021, 4678 patients underwent thyroid surgery were collected. Of these patients, 440 were diagnosed with HT (242 nodular goiter (NG) with HT, 198 TC with HT). These patients were grouped when appropriate and the data from these patients were statistically analyzed by using SPSS and GraphPad Prism 6. Results: HT occurred in 198 of 1089 (18.2%) TC patients and 242 of 3589 (6.74%) patients without TC (p=0.000). In terms of the ultrasonography features, in the NG with HT group, 33.1% (80/242) of patients had fine calcification and 45.9% (111/242) of patients whose TI-RADS classification were > Level 3. In the isolated PTC group, 32.3% (2343/7260) LN were metastasis-positive while in the NG with HT group, only 26.0% (504/1939) LN were metastasis-positive (P=0.000). The proportion of PTMC was significantly higher (P=0.000), while the proportion of multifocal carcinoma was significantly lower when coexisting with HT (P=0.029). When comparing the data from the two groups diagnosed as PTMC coexisting with HT or not, there was no significant difference in the composition ratio of tumor number, LN metastasis, LN dissection area, regional LN metastasis and number of negative/positive LN (P=0.614, P=0.051, P=0.139, P=0.350, P=1.000 and P=0.333 respectively). In the MPTC group, 42.2% (872/2065) LN were metastasis-positive while in the MPTC with HT group, only 23.6% (50/212) LN were metastasis-positive (P=0.000). Conclusions: Our data suggested that HT is associated with an increased risk of developing TC but may be a protective factor against PTC progression and metastasis. The coexistence of HT affects the judgment of thyroid nodules by ultrasonography.
