PTEN mutation predicts unfavorable fertility preserving treatment outcome in the young patients with endometrioid endometrial cancer and atypical hyperplasia.

OBJECTIVE: This study aimed to investigate the impact of molecular classification and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment in the patients with endometrioid endometrial cancer (EEC) and endometrial atypical hyperplasia (EAH). METHODS: This is a single-center retrospective study. A total of 135 patients with EEC and EAH receiving fertility-preserving treatment and molecular classification were reviewed. The distribution of the four types of molecular classification was described. The impact of non-specific molecular profile (NSMP), mismatch repair-deficiency (MMRd), and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment was analyzed. RESULTS: Of the patients analyzed, 86.7% (117/136) were classified as having NSMP; 14 (10.4%), MMRd; 1 (0.7%), POLEmut EAH; and 3 (2.2%), p53abn EEC. The patients having NSMP and MMRd achieved similar 16-, 32-, and 48-week complete response rates. The patients harboring tier I and tier II PTEN mutations (PTENmut-Clin) achieved lower cumulative 32-week CR rates than those with PTEN-others (without PTENmut-Clin) (22/47, 46.8% vs. 50/74, 67.6%; p=0.023; odds ratio=0.422; 95% confidence interval [CI]=0.199-0.896). Insulin-resistance (hazard ratio [HR]=0.435; 95% CI=0.269-0.702; p=0.001) and PTENmut-Clin (HR=0.535; 95% CI=0.324-0.885; p=0.015) were independent negative predictors for lower 32-week CR rates. CONCLUSION: PTENmut-Clin is an independent risk factor for unfavorable fertility-preserving treatment outcomes in the patients with EEC and EAH. The patients with MMRd receiving fertility-preserving treatment achieved outcomes similar to those of the patients with NSMP. The molecular profiles might guide fertility-preserving treatment in the prognosis and clinical decisions.

Identification of Serpin peptidase inhibitor clade A member 1 (SERPINA1) might be a poor prognosis biomarker promoting the progression of papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most prevalent malignancy within the endocrine system, exhibiting a rapid growth rate in recent years. Serpin peptidase inhibitor clade A member 1 (SERPINA1) has been previously proposed as a diagnostic biomarker; however, it's potential molecular relevance and biological function in PTC remains largely unexplored. METHODS: Our study utilized multi-omics bioinformatic data from several public databases, supplemented with transcriptional profiles using our local cohort comprising 79 paired PTC samples. RESULTS: Using multi-omics profiling of a PTC cohort, we have identified SERPINA1 as a potential oncogene involved in PTC progression. Our clinical analysis revealed a significant association between SERPINA1 expression and mutations in BRAFV600E and RAS. Furthermore, SERPINA1 level was correlated with clinicopathological factors in patients with PTC and with a worse prognosis in early-stage patients. Functionally, we found a strong correlation between SERPINA1 expression and increased infiltration of dendritic cells and regulatory T-cells, suggesting an elevated level of immune infiltration. Moreover, SERPINA1 knockdown reduced the proliferative and migrational ability of PTC cells in vitro. CONCLUSION: Our study highlights the high expression of SERPINA1 in PTC and its potential role in shaping the immune microenvironment, thereby promoting disease progression. These findings suggest that SERPINA1 could serve as a promising therapeutic target for intervention in PTC.

Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer.

Breast cancer (BC) is one of the most common malignancies among women worldwide. It is necessary to search for improvement in diagnosis and treatment methods to improve the prognosis. Protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, has been studied in some tumors except BC. This study has explored that PKMYT1 functional role by bioinformatics methods combined with local clinical samples and experiments. Comprehensive analysis showed that PKMYT1 expression was higher in BC tissues, especially in advanced patients than that in normal breast tissues. The expression of PKMYT1 was an independent determinant for BC patients' prognosis when combined with the clinical features. In addition, based on multi-omics analysis, we found that the PKMYT1 expression was closely relevant to several oncogenic or tumor suppressor gene variants. The analysis of single-cell sequencing indicated that PKMYT1 expression was upregulated in triple-negative breast cancer (TNBC), consistent with the results of bulk RNA-sequencing. High PKMYT1 expression was correlated with a poor prognosis. Functional enrichment analysis revealed that PKMYT1 expression was associated with cell cycle-related, DNA replication-related, and cancer-related pathways. Further research revealed that PKMYT1 expression was linked to immune cell infiltration in the tumor microenvironment. Additionally, loss-of-function experiments in vitro were performed to investigate the role of PKMYT1. TNBC cell lines' proliferation, migration, and invasion were inhibited when PKMYT1 expression was knock-down. Besides, the down-regulation of PKMYT1 induced apoptosis in vitro. As a result, PKMYT1 might be a biomarker for prognosis and a therapeutic target for TNBC.

A retrospective analysis of GSE84010: Cell adhesion molecules might contribute to bevacizumab resistance in glioblastoma.

Bevacizumab (BEV) is an anti-angiogenesis antibody which has shown favorable therapeutic effects on some solid tumors. However, many clinical trials showed that BEV could only improve PFS instead of OS in glioblastoma (GBM) patients. However, some studies indicate that specific molecular subtypes of GBM could still benefit from combination treatment of BEV and Stupp protocol. Through the subgroup analysis of GSE84010 dataset, we found the neural and proneural subgroup can benefit from the administration of BEV in terms of OS, which is statistically significant. The further KEGG pathway enrichment analysis showed cell adhesion molecules (CAMs) pathway was enriched, and the expression of ITGAM has a predictive value for prognosis. These findings can provide some hints for future administration of BEV in newly diagnosed GBM patients.