The multifaceted functions of NFE2L1 in metabolism and associated disorders.

Nuclear factor erythroid 2-related factor 1 (NFE2L1, also known as Nrf1) is a crucial member of the CNC-bZIP subfamily of transcription factors expressed ubiquitously throughout our body. Recent findings have revealed its association with various metabolic processes, encompassing glucose, lipid, and protein metabolism. In the realm of glucose metabolism, NFE2L1 exerts regulatory control by modulating pancreatic ß cells and insulin production. It also influences glucose metabolism in liver and the insulin sensitivity of adipose tissue. Regarding lipid metabolism, NFE2L1 governs this process by influencing the expression of specific adipogenic and lipolysis genes in both liver and adipose tissue. Additionally, NFE2L1 regulates specific lipids, such as cholesterol. These involvements underlie various manifestations of NFE2L1 deficiency such as adipocyte hypertrophy, inflammation, and steatohepatitis. In the realm of protein metabolism, NFE2L1 serves as a major transcription factor regulating the 26S proteasome genes expression, which dysfunction has been related with multiple diseases including neurodegenerative diseases, cancers, autoimmune conditions, etc. In this comprehensive review, we summarize the diverse roles that NFE2L1 plays in glucose, lipid, and protein metabolism, as well as its impact on diseases related to these metabolic processes.

Effects of Breast-Conserving Surgery and Mastectomy on the Survival of Patients with Early-Stage (T1-2N0-1M0) HER2-Positive Breast Cancer: A Propensity Score-Matched Analysis.

INTRODUCTION: Although breast-conserving therapy (BCT) promises at least a similar survival rate for patients with early breast cancer compared with mastectomy, its efficacy in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors remains unclear. Therefore, we conducted this study to explore differential effects of BCT and mastectomy on survival outcomes of patients with early-stage HER2-positive breast cancer. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and basic characteristics of patients who received either BCT or mastectomy were balanced using propensity score matching (PSM). Kaplan-Meier analysis, log-rank testing, and Cox proportional hazards regression were performed. RESULTS: In total, 20,277 patients were diagnosed with T1-2N0-1M0 HER2-positive breast cancer between 2010 and 2015. After PSM, 6,185 pairs of patients were enrolled for further analysis. Compared with those undergoing mastectomy, patients receiving BCT had superior overall survival (OS) (hazard ratio [HR], 0.63; 95% confidence interval [CI]: 0.55-0.73; p < 0.001) and breast cancer-specific survival (BCSS) (HR: 0.59; 95% CI: 0.48-0.71; p < 0.001). The subgroup analyses revealed that survival outcomes (OS and BCSS) of BCT were better than those of mastectomy among estrogen receptor (ER)+/progesterone receptor (PR)+/HER2+, ER+/PR-/HER2+, and ER-/PR-/HER2+ subtypes (p < 0.05 for all); however, patients with ER-/PR+/HER2+ subtypes who underwent BCT had similar OS and BCSS (p > 0.05 for both) to those treated with mastectomy. DISCUSSION/CONCLUSION: Despite the aggressiveness of the disease, we found that BCT may confer better long-term survival than mastectomy for patients with T1-2N0-1M0 HER2-positive breast cancer, particularly for those with ER+/PR+/HER2+, ER+/PR-/HER2+, and ER-/PR-/HER2+ subtypes. In addition, our study provided insights into the clinical applications of BCT. However, this retrospective study has introduced several inevitable limitations, and further prospective research is warranted to verify these conclusions.

Lymph Nodes Dissection in Elderly Patients with T3-T4 Laryngeal Cancer.

OBJECTIVE: To explore the survival value of lymph node dissection (LND) in elderly patients with T3-T4 laryngeal cancer, analyze the risk factors of lymph node metastasis, and construct a preoperative prediction model. MATERIALS AND METHODS: The study included 996 patients aged ≥65 years with laryngectomy confirmed T3-T4 laryngeal cancer queried from Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2017. Propensity score matching (PSM) was applied to balance the effects of confounding factors. Kaplan-Meier (K-M) analysis and competitive risk model were used to compare the overall survival (OS) and cancer-specific survival (CSS) between LND and no-LND (N-LND) group. Combined with risk factors of multivariate logistic regression, a nomogram was built to predict lymph node metastasis preoperatively. The performance was assessed in the training set and the validation set, and internal validation was assessed. RESULTS: Among the cohort, 822 patients underwent LND and 410 patients had positive lymph nodes. The OS and CSS of patients who underwent LND were not better than that of N-LND patients (P>0.05). The prognosis of patients with lymph node metastases was significantly worse than that of negative patients (P<0.05). On multivariate logistic regression, supraglottis cancer, tumor size >5cm and grade 3-4 classification were associated with significantly greater odds of lymph node metastasis. The nomogram showed favorable predictive efficacy and good calibration (in the training cohort C-index=0.700; in the validation cohort C-index=0.721). CONCLUSION: For elderly patients with T3-T4 laryngeal cancer, LND did not bring significant survival values. Supraglottis cancer, tumor size >5cm and grade 3-4 classification were independent risk factors of lymph node metastasis, which means poor prognosis. The nomogram developed was an easy-to-use tool for lymph node prediction.

[Significance of TSLC1 gene methylation and TSLC1 protein expression in the progression of cervical lesions].

OBJECTIVE: To study the expression and significance of tumor suppressor in lung cancer 1 (TSLC1) gene methylation, the expression of TSLC1 protein in cervix cancer and precancerous lesions as well as their relationship with HR-HPV DNA infection. METHODS: The clinicopathological data of 92 cases of different cervical lesions during March 2011 to August 2012 treated in our hospital were collected. There were pathologically confirmed 10 cases of normal cervix, 26 cases of cervical intraepithelial neoplasia (CIN) I, 20 cases of CIN II, 15 cases of CIN III, and 21 cases of cervical cancer. Methylation-specific polymerase chain reaction (MSP) was used to detect the TSLC1 gene methylation status in cervical lesions, immunohistochemistry (SP) was used to detect the expressions of TSLC1 protein in cervical lesions, and the second generation hybrid capture (HC2) method was used to detect the high-risk HPV in cervical lesions. RESULTS: The expression rate of TSLC1 gene methylation in normal cervical tissue, CIN I, CIN II, CIN III and SCC were 10.0%, 30.8%, 55.0%, 60.0%, 66.7%, respectively, showing a statistically significant difference (P = 0.004). The positive expression rate of TSLC1 protein in normal cervical tissue, CIN I, CIN II, CIN III and SCC were 100.0%, 80.8%, 65.0%, 33.3%, and 23.8%, respectively, with a significant difference (P = 0.004). In the progression from CIN to invasive cervical cancer, there was no significant correlation between TSLC1 gene methylation and HR-HPV DNA infection (P = 0.919), TSLC1 protein expression and HR-HPV DNA infection (P = 0.664). The correlation analysis showed a negative correlation between TSLC1 gene methylation and TSLC1 protein expression (r = -0.674, P < 0.001). CONCLUSIONS: TSLC1 gene promoter methylation may be an early event in the cervical carcinogenesis, become an early sensitive marker, and serve the early prevention and prognostic prediction for cervical cancer.

Human telomerase gene and high-risk human papillomavirus infection are related to cervical intraepithelial neoplasia.

Our aims were to evaluate the clinical performance of human telomerase RNA gene component (hTERC gene) amplification assay with high-risk human papillomavirus (HR-HPV) DNA test of Hybrid Capture 2 DNA test (HC2), for the detection of high grade cervical precancerous lesions and cancer (CIN 2+). In addition, the association shown between hTERC gene amplification and HPV DNA test positive in women with and without cervical neoplasia was assessed. There were 92 women who underwent cytology, HR-HPV DNA test, hTERC gene amplification test, colposcopy and biopsy. We compared the clinical performance of hTERC gene test along with HR-HPV DNA test of women with colposcopy and routine screening. The samples were histology- confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN2+) as the positive criterion. The test of hTERC gene showed the hTERC gene amplification positivity increased with the severity of histological abnormality and cytological abnormality. The test of hTERC gene showed higher specificity than HR-HPV DNA test for high-grade lesions (84.4% versus 50%) and also higher positive predictive value (90.4% versus 76.5%). Our results predicted that hTERC gene amplification demonstrated more specific performance for predicting the risk of progression and offer a strong potential as a tool for triage in cervical cancer screening, with the limited sensitive as HR-HPV DNA test.

Serum HE4 is more suitable as a biomarker than CA125 in Chinese women with benign gynecologic disorders.

OBJECTIVE: This study measured the human epididymis protein 4 (HE4) and CA125 levels in Chinese women with benign gynecological disorders. MATERIAL AND METHODS: Sera were obtained from Chinese women prior to surgery for a pelvic mass and HE4 and CA125 levels were determined. The proportions of patients with HE4 and CA125 levels were compared. RESULTS: There were 68 Chinese women with benign diseases. HE4 levels were less elevated than CA125 (1% V.S. 29%, P<0.001). The significant difference was observed in patients with endometriosis/endometriomas in which HE4 was not elevated patients and CA125 was elevated in 53% (P<0.001). Serum HE4 level was not elevated in patients with cystadenoma (0% V.S. 23%, P<0.001) and in patients with germ cell tumors (0% V.S. 5%, P<0.001). CONCLUSION: HE4 was less elevated and more suitable as a biomarker than CA125 in chinese women with benign disease.

[Comparative study of HR HPV E6/E7 mRNA and HR-HPV DNA in cervical cancer screening].

OBJECTIVE: To determine the performance of HR-HPV E6/E7 massager RNA (mRNA) test for detecting high-grade cervical intraepithelial neoplasia in cervical cancer screening and compare the clinical performance of HR-HPV E6/E7 mRNA test with HC-2 and Cervista HPV DNA tests for cross-sectional positivity in women with and without cervical neoplasia. METHODS: A total of 172 women underwent cytology, HR-HPV DNA test, HR-HPV E6/7 mRNA test, colposcopy and biopsy. We compared the clinical performance of HR-HPV E6/E7 mRNA test with Hybrid Capture 2 DNA test (HC-2) and Cervista HR-HPV DNA test on the cervical brush specimens during colposcopy and routine screening. The samples were histologically confirmed high-grade cervical intraepithelial neoplasia (CIN II) or worse (CIN II+) as an endpoint. RESULTS: HR-HPV E6/E7 mRNA positive rate was 37.9% in NILM, 67.9% in ASCUS and LSIL, 88.5% in ASC-H+. HR-HPV E6/E7 mRNA positive rate was 38.6% in CIN I, 77.4% in CIN II-3 and 92.5% in SCC. HR-HPV E6/E7 mRNA test showed a higher specificity than HC-2 and Cervista HPV DNA tests for high-grade lesions (61.4%, 54.3%, 55.7%, respectively, P < 0.05) and also a higher positive predictive value (75.9%, 74.8%, 74.6% respectively). Among three tests, HR-HPV E6/E7 mRNA had the largest area of ROC curve and the best diagnostic value. CONCLUSION: HR-HPV E6/E7 mRNA test has a performance more specific for detecting CIN II+ with the same sensitivity as HC-2 and Cervista HPV DNA tests. And it may serve as a more specific test for predicting the risk of progression and offer a viable tool for triage during cervical cancer screening.

[Expression of GLUT-1, p63 and DNA-Pkcs in serous ovarian tumors and their significance].

OBJECTIVE: To investigate the expression of GLUT1, p63 and DNA-Pkcs in serous ovarian tumors and their significance. METHODS: GTUL1, p63 and DNA-Pkcs expression at protein level was detected by immunohistochemistry in patients with serous ovarian tumors. Chi-square analysis was used to assess if their expression is associated with clinicopathologic characteristics of the tumors. RESULTS: Cells in the normal ovarian tissues were not stained with GTUL1 and p63 antiserum, but DNA-Pkcs was positively stained. The intensity of GTUT1 and p63 expression was stronger in malignant ovarian serous tumors compared with other subtypes (P < 0.01). There were significant differences of DNA-PKcs among normal ovaries (100.0%), benign (95.0%), borderline (90.0%) and malignant (60.0%) serious ovarian neoplasms (P < 0.01). The level of GLUT-1 expression was correlated with FIGO staging, intraperitoneal implantation, ascites and lymph node metastasis (P < 0.05). p63 expression was associated with clinicopathologic characteristics except ascites (P < 0.05). DNA-PKcs was only correlated with FIGO staging and lymph node metastasis (P < 0.05). CONCLUSION: The results suggest that the abnormal expression of GTUT1, p63 and DNA-Pkcs may perhaps participate in serous ovarian tumor occurrence and development and may be considered as a marker reflecting tumor malignant behavior.