Prognostic Value of PTENP1 Expression in Patients with Cancer: a Systematic Review and Meta-Analysis.

BACKGROUND: Downregulation of PTENP1 was reported in different malignant tumors. However, the function and significance of PTENP1 in the clinical pathology and prognosis of tumors are not very clear. Therefore, we performed this research to analyze and elucidate the correlations between the PTENP1 expression and clinical pathological parameters and outcome of patients in different types of cancer. METHODS: Literature on PTENP1 was retrieved from PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wan Fang, Springer, Ovid, and Medline databases. Pooled ORs (odds ratios) or HRs (hazard ratios) with 95% CIs were utilized to examine the relationship between the PTENP1 and clinical pathological traits and outcome of patients with different tumor types. RESULTS: Eight studies comprising 1,047 patients were enrolled and analyzed in this research. Down-regulation of PTENP1 was correlated with differentiation (OR: 2.57; 95% CI: 1.14 - 5.80), TNM stage (OR: 0.24; 95% CI: 0.13 - 0.43), and LNM (OR: 0.27; 95% CI: 0.14 - 0.52). Moreover, PTENP1 expression level was correlated with OS in the eight types of tumors (pooled HR: 0.49; 95% CI: 0.39, 0.61). CONCLUSIONS: Low expression of PTENP1 might predict poor prognosis in patients with various carcinomas. PTENP1 may play an important role as a new prognostic indicator in patients with different malignant tumors.

Tumor microenvironment-related multigene prognostic prediction model for breast cancer.

BACKGROUND: Breast cancer is an invasive disease with complex molecular mechanisms. Prognosis-related biomarkers are still urgently needed to predict outcomes of breast cancer patients. METHODS: Original data were download from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The analyses were performed using perl-5.32 and R-x64-4.1.1. RESULTS: In this study, 1086 differentially expressed genes (DEGs) were identified in the TCGA cohort; 523 shared DEGs were identified in the TCGA and GSE10886 cohorts. Eight subtypes were estimated using non-negative matrix factorization clustering with significant differences seen in overall survival (OS) and progression-free survival (PFS) (P < 0.01). Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to develop a related risk score related to the 17 DEGs; this score separated breast cancer into low- and high-risk groups with significant differences in survival (P < 0.01) and showed powerful effectiveness (TCGA all group: 1-year area under the curve [AUC] = 0.729, 3-year AUC = 0.778, 5-year AUC = 0.781). A nomogram prediction model was constructed using non-negative matrix factorization clustering, the risk score, and clinical characteristics. Our model was confirmed to be related with tumor microenvironment. Furthermore, DEGs in high-risk breast cancer were enriched in histidine metabolism (normalized enrichment score [NES] = 1.49, P < 0.05), protein export (NES = 1.58, P < 0.05), and steroid hormone biosynthesis signaling pathways (NES = 1.56, P < 0.05). CONCLUSIONS: We established a comprehensive model that can predict prognosis and guide treatment.

Pan-cancer analysis of the angiotensin II receptor-associated protein as a prognostic and immunological gene predicting immunotherapy responses in pan-cancer.

Background: Understanding interior molecular mechanisms of tumorigenesis and cancer progression contributes to antitumor treatments. The angiotensin II receptor-associated protein (AGTRAP) has been confirmed to be related with metabolic products in metabolic diseases and can drive the progression of hepatocellular carcinoma and colon carcinoma. However, functions of AGTRAP in other kinds of cancers are unclear, and a pan-cancer analysis of AGTRAP has not been carried out. Methods and materials: We downloaded data from The Cancer Genome Atlas and Genotype-Tissue Expression dataset and The Human Protein Atlas databases and then used R software (version 4.1.1) and several bioinformatic tools to conduct the analysis. Results: In our study, we evaluated the expression of AGTRAP in cancers, such as high expression in breast cancer, lung adenocarcinoma, and glioma and low expression in kidney chromophobe. Furthermore, our study revealed that high expression of AGTRAP is significantly related with poor prognosis in glioma, liver cancer, kidney chromophobe, and so on. We also explored the putative functional mechanisms of AGTRAP across pan-cancer, such as endoplasmic reticulum pathway, endocytosis pathway, and JAK-STAT signaling pathway. In addition, the connection between AGTRAP and tumor microenvironment, tumor mutation burden, and immune-related genes was proven. Conclusion: Our study provided comprehensive evidence of the roles of AGTRAP in different kinds of cancers and supported the relationship of AGTRAP and tumorous immunity.

The Application Value of the Central Lymph Node Metastasis Risk Assessment Model in Papillary Thyroid Microcarcinoma of Stage cN0: A Study of 828 Patients.

Background: The aim of this study is to build a risk assessment system for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC) of stage cN0 and to explore its application value in clinical practice. Methods: A total of 500 patients with PTMC who underwent thyroid operation from 2013 to 2015 in Ningbo First Hospital were selected as the model group. Independent risk factors related to CLNM in PTMC were analyzed and determined, and a risk assessment system for CLNM was preliminarily established. Furthermore, the clinicopathological data from 328 PTMC patients with the same conditions as the model group from 2016 to 2017 were further collected as the validation group to verify the diagnostic value of the risk assessment system. Results: The risk assessment system was based on the score rating (score ≤ 5 was classified as low risk, 6-8 was classified as medium risk, and ≥9 was classified as high-risk). The area under the receiver operating characteristic curve (ROC) was 0.687 (95% CI: 0.635-0.783). According to the risk assessment system, 328 PTMC patients in the validation group were scored. Among the low-risk group, the moderate-risk group, and the high-group, 96.8%, 58.1%, and 43.2% were the CLNM (-) patients, and 3.1%, 41.9%, and 65.8% were CLNM (+) patients, respectively. The area under ROC was 0.837 (95% CI: 0.778-0.869). Conclusions: The risk assessment system in this study is of diagnostic value and can provide a theoretical foundation for intraoperative decision-making of prophylactic central neck dissection (pCND).

Neoadjuvant Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors Combined with Endocrine Therapy in HR+/HER2- Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Cyclin-dependent kinase (CDK) 4/6 inhibitors have been advocated for adjuvant therapy of metastatic hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- breast cancer (BC). However, the efficiency of adding CDK 4/6 inhibitors to neoadjuvant therapy was not unequivocal. OBJECTIVE: The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2- BC. METHOD: We searched PubMed, the Cochrane Library, Web of Science, and Embase online databases for randomized controlled trials and single-arm studies written in English until April 2021. RESULTS: Five studies comparing CDK 4/6 inhibitors + ET as neoadjuvant treatments to ET alone and 2 studies comparing neoadjuvant CDK 4/6 inhibitors + ET to neoadjuvant chemotherapy were analysed. Neoadjuvant CDK 4/6 inhibitors + ET improved the rate of complete cell cycle arrest (CCCA: central Ki67 < 2.7%, odds ratio [OR] = 7.91, 95% confidence interval [CI] = 4.81-13.03, p < 0.001), increased the risk of adverse events (AEs; especially ≥3 AEs; AEs of all grades: OR = 9.10, 95% CI = 2.39-34.58, p = 0.001; AEs ≥3: OR = 12.24, 95% CI = 4.17-35.88, p < 0.001), led to no significant differences in pathological complete response (pCR) in patients with BC (OR = 0.34, 95% CI = 0.04-2.85, p = 0.318) compared to endocrine monotherapy. Moreover, subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59-29.61, p < 0.001; palbociclib: OR = 7.39, 95% CI = 1.26-43.40, p = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41-20.11, p < 0.001). Compared to neoadjuvant chemotherapy, neoadjuvant CDK 4/6 inhibitors plus ET decreased the risk of AEs ≥3 (OR = 0.50, 95% CI = 0.29-0.87, p = 0.015) and showed similar ability to reach pCR (OR = 0.50, 95% CI = 0.12-2.07, p = 0.342) and reduce the residual cancer burden (RCB, RCB 0-1: OR = 0.47, 95% CI = 0.18-1.22, p = 0.121; RCB 2-3: OR = 2.30, 95% CI = 0.89-5.91, p = 0.084). CONCLUSIONS: The results suggested that combination therapy had increased efficacy and toxicity compared to endocrine monotherapy and showed similar efficacy to and better safety than neoadjuvant chemotherapy.

DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is a subtype of breast cancer with strong aggressiveness and poor clinical treatment effect, accounting for about 10-20% of breast cancer cases. N(6)-methyldeoxyadenosine (6mA) is the most conservative DNA modification in prokaryotes and eukaryotes. It is widely found in bacteria and has such functions as DNA mismatch repair, chromosome separation and virulence regulation. We determined that 6mA was modified in TNBC cell line MDA-MB-231 and the TNBC tissue. Meanwhile, compared with normal tissues, the expression level of 6mA and its methylase N6AMT1 was significantly decreased in TNBC tissue. MDA-MB-231cells were cultured with 8µM Olaparib for 2 months to construct drug-resistant cell line 231-RO. It was found that the level of 6mA also increased significantly, and the expression of N6AMT1 or ALKBH1 could effectively influence the drug resistance. Subsequently, we found that LINP1 was highly expressed in 231-RO, which was involved in DNA repair, and the expression of LINP1 could be positively regulated by 6mA modification. LINP1 expression level is directly related to TNBC drug resistance. The above results indicate that 6mA may be a new biological marker of TNBC. Meanwhile, 6mA modification may be involved in the regulation of Olaparib resistance.

Prognostic role of methylated GSTP1, p16, ESR1 and PITX2 in patients with breast cancer: A systematic meta-analysis under the guideline of PRISMA.

BACKGROUND: BRCA1 and RASSF1A promoter methylation has been reported to be correlated with a worse survival in patients with breast cancer. However, the prognostic values of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer remain to be determined. Here, we performed this study to evaluate the prognostic significance of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer. METHODS: A range of online databases was systematically searched to identify available studies based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. The pooled hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were applied to estimate the prognostic effect of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer for multivariate regression analysis. RESULTS: 13 eligible articles involving 3915 patients with breast cancer were analyzed in this meta-analysis. In a large patient population, GSTP1 showed a trend toward a worse prognosis in overall survival (OS) (HR = 1.64, 95% CI = 0.93-2.87, P = .085). PITX2 promoter methylation was significantly correlated with a worse prognosis in OS (HR = 1.57, 95% CI = 1.15-2.14, P = .004), but no association between p16 promoter methylation and OS (HR = 0.92, 95% CI = 0.31-2.71, P = .884). PITX2 promoter methylation was significantly correlated with an unfavorable prognosis of patients with breast cancer in metastasis-free survival (MFS) (HR = 1.73, 95% CI = 1.33-2.26, P < .001). The result from 3 studies with 227 cases showed that ESR1 promoter methylation was linked to a worse prognosis in OS (HR = 1.55, 95% CI = 1.06-2.28, P = .025). CONCLUSIONS: Our findings suggest ESR1 and PITX2 promoter methylation may be correlated with a worse survival of patients with breast cancer (ESR1: OS, PITX2: OS and MFS). The clinical utility of aberrantly methylated ESR1 and PITX2 could be a promising factor for the prognosis of breast cancer.