A prognostic model based on CLEC6A predicts clinical outcome of breast cancer patients.

CLEC6A, (C-type lectin domain family 6, member A), plays a prominent role in regulating innate immunity and adaptive immunity. CLEC6A has shown great potential as a target for cancer immunotherapy. This study aims to explore the prognostic value of CLEC6A, and analyze the relationship associated with the common hematological parameters in breast cancer patients. We performed a retrospective analysis on 183 breast cancer patients data in hospital information system from January 2013 to December 2015. The expression of CLEC6A was recorded via semiquantitative immunohistochemistry in breast cancer. The association between expression of CLEC6A and relative parameters were performed by Chi-square test and Fisher's exact test. Kaplan-Meier assay and Log-rank test were performed to evaluate the survival time. The Cox proportional hazards regression analysis was applied to identify prognostic factors. Nomograms were conducted to predict 1-, 3-, and 5-year disease free survival (DFS) and overall survival (OS) for breast cancer, which could be a good reference in clinical practice. The nomogram model was estimated by calibration curve analysis for its function of discrimination. The accuracy and benefit of the nomogram model were appraised by comparing it to only CLEC6A via decision curve analysis (DCA). The prediction accuracy of CLEC6A was also determined by time-dependent receiver operating characteristics (TDROC) curves, and the area under the curve (AUC) for different survival time. There were 94 cases in the CLEC6A low-expression group and 89 cases in CLEC6A high-expression group. Compared to CLEC6A low-expression group, the CLEC6A high-expression group had better survival (DFS: 56.95 vs. 70.81 months, P = 0.0078 and OS: 67.98 vs. 79.05 months, P = 0.0089). The CLEC6A was a potential prognostic factor in multivariate analysis (DFS: P = 0.023, hazard ratio (HR): 0.454, 95 % confidence interval (CI): 0.229-0.898; OS: P = 0.020, HR: 0.504, 95 %CI: 0.284-0.897). The nomogram in accordance with these potential prognostic factors was constructed to predict survival and the calibration curve analysis had indicated that the predicted line was well-matched with reference line in 1-, 3-, and 5-year DFS and OS category. The 1-, 3-, and 5-year DCA curves have revealed that nomogram model yielded larger net benefits than CLEC6A alone. Finally, the TDROC curve indicated that CLEC6A could better predict 1-year DFS and OS than others. Furthermore, we combined these potential independent prognostic factors to analyze the relationship among these hematologic index and oxidative stress indicators, and indicated that higher CLEC6A level, higher CO2 level or low CHOL level or high HDL-CHO level would have survived longer and better prognosis. In breast cancer, high expression of CLEC6A can independently predict better survival. Our nomogram consisted of CLEC6A and other indicators has good predictive performance and can facilitate clinical decision-making.

Comparison of health-related quality of life and cosmetic outcome between traditional gasless trans-axillary endoscopic thyroidectomy and modified gasless trans-axillary endoscopic thyroidectomy for patients with papillary thyroid microcarcinoma.

BACKGROUND: Gasless trans-axillary endoscopic thyroidectomy (GTET) has been proved to provide better cosmetic results; however, it has limitations as dissection of central neck lymph nodes is difficult. We developed a modified approach (MGTET-modified GTET) and compared it with the traditional one in terms of patients' health-related quality of life (HRQoL) and cosmetic results in order to provide more convincing therapeutic results. METHODS: Between January 2021 and June 2021, 100 cN0 patients who had a confirmed diagnosis of papillary thyroid microcarcinoma were randomized to undergo either MGTET (n = 50) or GTET (n = 50). These two groups' baseline characteristics, intraoperative and postoperative findings, were compared. The Patient and Observer Scar Assessment Scale (POSAS) was determined 6 months after surgery. Thyroid Cancer-Specific Quality of Life Questionnaire was used to assess HRQoL at 1, 3, 6, and 12 months after surgery. RESULTS: M-GTET was associated with a larger number of lymph nodes dissected (p < 0.001), lower drainage volume (p < 0.001), shorter hospital stay (p < 0.001), and shorter axillary incision (p < 0.001). POSAS was more favorable in M-GTET. HRQoL was significantly better for MGTET in terms of less problems with scar (p < 0.001). CONCLUSION: Our study suggests that MGTET provides better therapeutic, cosmetic, and HRQoL outcomes.

Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery.

BACKGROUND: Recurrent and metastatic thyroid cancer is more invasive and can transform to dedifferentiated thyroid cancer, thus leading to a severe decline in the 10-year survival. The thyroid-stimulating hormone receptor (TSHR) plays an important role in differentiation process. We aim to find a therapeutic target in redifferentiation strategies for thyroid cancer. METHODS: Our study integrated the differentially expressed genes acquired from the Gene Expression Omnibus database by comparing TSHR expression levels in the Cancer Genome Atlas database. We conducted functional enrichment analysis and verified the expression of these genes by RT-PCR in 68 pairs of thyroid tumor and paratumor tissues. Artificial intelligence-enabled virtual screening was combined with the VirtualFlow platform for deep docking. RESULTS: We identified five genes (KCNJ16, SLC26A4, TG, TPO, and SYT1) as potential cancer treatment targets. TSHR and KCNJ16 were downregulated in the thyroid tumor tissues, compared with paired normal tissues. In addition, KCNJ16 was lower in the vascular/capsular invasion group. Enrichment analyses revealed that KCNJ16 may play a significant role in cell growth and differentiation. The inward rectifier potassium channel 5.1 (Kir5.1, encoded by KCNJ16) emerged as an interesting target in thyroid cancer. Artificial intelligence-facilitated molecular docking identified Z2087256678_2, Z2211139111_1, Z2211139111_2, and PV-000592319198_1 (-7.3 kcal/mol) as the most potent commercially available molecular targeting Kir5.1. CONCLUSION: This study may provide greater insights into the differentiation features associated with TSHR expression in thyroid cancer, and Kir5.1 may be a potential therapeutic target in the redifferentiation strategies for recurrent and metastatic thyroid cancer.

Golgi Membrane Protein 1 (GOLM1) Promotes Growth and Metastasis of Breast Cancer Cells via Regulating Matrix Metalloproteinase-13 (MMP13).

BACKGROUND Breast cancer (BC) is the leading cause of death in women worldwide. Golgi membrane protein 1 (GOLM1) has been identified as novel regulator in carcinogenesis, but its function in BC is unclear. MATERIAL AND METHODS The expression of GOLM1 in BC tissues and cell lines was detected by using qRT-PCR assay. CCK-8 and colony-formation assays were used to evaluate BC cell growth in vivo. Wound-healing and Transwell assays were used to detect cell migration and invasion. To investigate GOLM1 functions in vivo, we established a xenograft mice model and a lung metastasis model. The level of epithelial-to-mesenchymal transition (EMT)-related markers was analyzed by immunofluorescent staining. RESULTS GOLM1 was overexpressed in BC cell lines and tissues. Overexpression of GOLM1 induced EMT and promoted proliferation, migration, and invasion of BC cells. Furthermore, overexpressing of GOLM1 markedly promoted the tumorigenicity and metastasis of BC cells in vivo, whereas knock-down of GOLM1 caused the opposite outcomes. Furthermore, we proved that GOLM1 promoted BC cell aggressiveness by regulating matrix metalloproteinase-13 (MMP13). CONCLUSIONS Our results prove that GOLM1 facilitates the growth and metastasis of breast cancer cells.