FSTL1 is a protein coding gene associated with cell signaling pathway regulation and the progression of a variety of disorders. In this study, we hypothesized that FSTL1 increases oncogenesis in breast cancer by enhancing stemness and chemoresistance. RT-PCR and IHC revealed significantly higher FSTL1 mRNA and protein levels in TNBC than in non-TNBC specimens and in breast cancer cell lines. We then found that FSTL1 levels were significantly increased in chemoresistant cells. LIVE/DEAD, MTT cell viability and colony formation assays did in fact demonstrate that FSTL1 is required for CDDP and DOX chemoresistance in breast cancer cell lines. FSTL1 overexpression caused significant elevation of stem cell biomarkers, as well as breast cancer cell proliferation. To determine whether the Wnt/β-catenin signaling pathway is involved in the observed effects of FSTL1, we assessed levels of pathway target. TOP/FOP flash, colony formation, and tumor sphere formation assays indicated that FSTL1 activates Wnt/β-catenin signaling through integrin β3. We then sought to identify a microRNA (miRNA) that regulates FSTL1 activity. Luciferase assays demonstrated that miR-137 reduces FSTL1 mRNA and protein levels. Ultimately, our findings indicate that there is an miR-137/FSTL1/integrin β3/Wnt/β-catenin signaling axis in breast cancer cells that regulates stemness and chemoresistance.

Although the prognostic value of programmed cell death-ligand 1 (PD-L1) expression in non-Hodgkin lymphoma (NHL) has been evaluated in many studies, the results remain controversial. To investigate the prognostic role of PD-L1 expression and the association between PD-L1 expression and clinicopathological features of NHL, we performed a meta-analysis. The PubMed, EMBASE, and Cochrane Library databases were searched up to November 30, 2017. The hazard ratio (HR), 95% confidence interval (CI), and odds ratios (OR) with 95% CIs were combined to evaluate the association of PD-L1 expression with overall survival (OS) and clinicopathological features. Review manager 5.3 and STATA 12.0 were used in this meta-analysis. A total of 2,005 patients across nine studies were enrolled in our meta-analysis, and the pooled results showed that high PD-L1 expression was associated with a poor prognosis (HR=2.04, 95% CI: 1.18-3.54, P=0.01). In the subgroup analysis according to histology types, pooled results demonstrated that an increased PD-L1 expression was an unfavorable prognostic factor for diffuse large B-cell lymphoma (HR=1.92, 95% CI: 1.06-3.48, P=0.03) but not for natural killer/T-cell lymphoma (HR=2.41, 95% CI: 0.47-12.22, P=0.29). Pooled ORs indicated that PD-L1 expression was higher in NHL with international prognostic indices of ≥3. However, PD-L1 expression had no correlation with gender, age, disease stage, lactate dehydrogenase level, B symptoms, and germinal center B-cell-like lymphoma. High PD-L1 expression was a poor prognostic biomarker in patients with NHL. Because of our limited sample size, high-quality studies with larger sample sizes are needed to validate our results.

Tamoxifen is a critical drug for the treatment of oestrogen receptor (ER)-positive breast cancer (BC), which represents the majority of BC subtypes. However, many BC tumours that initially respond eventually develop acquired Tamoxifen resistance. Bioinformatics analysis was conducted on genes affected by Tamoxifen and upregulated in Tamoxifen-resistant cells to identify the biological processes associated with Tamoxifen resistance. Metabolomics analysis was conducted to identify the metabolites that were altered in BC with tamoxifen resistance. Resistance to Tamoxifen was evaluated by cell viability, proliferation, invasion, and colony formation in vitro, and by tumour growth in vivo. Metabolomic profiling and the detection of relevant enzymes and metabolites corroborated the metabolic reprogramming towards glycolysis in tamoxifen - resistant BC. The produced lactic acid induced the lactylation of ZMIZ1. This post-translational modification at K843 (but not K537) increased protein stability by suppressing SUMOylation and ubiquitination. The elevated total level of ZMIZ1 increased the enrichment of ZMIZ1 binding to Nanog, resulting in increased transcriptional activity of Nanog, including in OCT4 and NPC2 genes. Therefore, it leads to increased stemness and cholesterol accumulation in Tamoxifen-resistant BC. Knockdown of ZMIZ1 impaired Tamoxifen resistance, but this effect was reversed by Nanog overexpression. In summary, this study identified an important mechanism underlying Tamoxifen resistance and revealed a potential association of glucose glycolysis with cholesterol metabolism through the ZMIZ1/Nanog/NPC2 axis.

Metaplastic breast cancer (MBC) is a rare and highly aggressive histological subtype of breast cancer. There remains a significant lack of precise predictive models available for use in clinical practice. This study utilized patient data from the SEER database (2010-2018) for data analysis. We utilized prognostic factors to develop a novel machine learning model (CatBoost) for predicting patient survival rates. Simultaneously, our hospital's cohort of MBC patients was utilized to validate our model. We compared the benefits of radiotherapy among the three groups of patients. The CatBoost model we developed exhibits high accuracy and correctness, making it the best-performing model for predicting survival outcomes in patients with MBC (1-year AUC = 0.833, 3-year AUC = 0.806; 5-year AUC = 0.810). Furthermore, the CatBoost model maintains strong performance in an external independent dataset, with AUC values of 0.937 for 1-year survival, 0.907 for 3-year survival, and 0.890 for 5-year survival, respectively. Radiotherapy is more suitable for patients undergoing breast-conserving surgery with M0 stage [group1: (OS:HR = 0.499, 95%CI 0.320-0.777 p < 0.001; BCSS: HR = 0.519, 95%CI 0.290-0.929 p = 0.008)] and those with T3-4/N2-3M0 stage undergoing mastectomy [group2: (OS:HR = 0.595, 95%CI 0.437-0.810 p < 0.001; BCSS: HR = 0.607, 95%CI 0.427-0.862 p = 0.003)], compared to patients with stage T1-2/N0-1M0 undergoing mastectomy [group3: (OS:HR = 1.090, 95%CI 0.673-1.750 p = 0.730; BCSS: HR = 1.909, 95%CI 1.036-3.515 p = 0.038)]. We developed three machine learning prognostic models to predict survival rates in patients with MBC. Radiotherapy is considered more appropriate for patients who have undergone breast-conserving surgery with M0 stage as well as those in stage T3-4/N2-3M0 undergoing mastectomy.

Peripheral T‐cell lymphoma (PTCL) is a highly aggressive type of non‐Hodgkin's lymphoma with a poor prognosis. Pyroptosis is a newly discovered procedural cell death mode, which has been implicated to occur in both tumor cells and immune cells. However, the occurrence and effect of pyroptosis on PTCL remain unclear. Here, we found that pyroptosis occurred in interstitial macrophages of PTCL rather than in tumor cells. In clinical specimens, macrophage pyroptosis was associated with a poor prognosis of PTCL. In vitro experiments and gene sequencing results showed that pyroptotic macrophages could upregulate the expression of TLR4 through secreting inflammatory cytokines IL‐18. Upregulated TLR4 activated its downstream NF‐κB anti‐apoptotic signaling pathway, thus leading to malignant proliferation and chemotherapy resistance of tumor cells. Moreover, the expression of factors such as XIAP in the NF‐κB anti‐apoptotic pathway was downregulated after the knockdown of TLR4, and the malignant promotion effect of pyroptotic macrophages on PTCL cells was also reversed. Our findings revealed the mechanism of pyroptotic macrophages promoting the malignant biological behavior of PTCL and elucidated the key role of TLR4 in this process. In‐depth analysis of this mechanism will contribute to understanding the regulatory effect of PTCL by the tumor microenvironment and providing new ideas for the clinical treatment of PTCL.

Background: Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play vital roles in human cancers. Nevertheless, the effects of lncRNAs and miRNAs on breast cancer (BC) remain to be further investigated. This study was designed to testify the roles of lncRNA antisense transcript of SATB2 protein (SATB2-AS1) and microRNA-155-3p (miR-155-3p) in BC progression. Methods: Levels of SATB2-AS1, miR-155-3p and breast cancer metastasis suppressor 1-like (BRMS1L) in BC were determined. The prognostic role of SATB2-AS1 in BC patients was assessed. The screened cells were respectively introduced with altered SATB2-AS1 or miR-155-3p to figure out their roles in malignant phenotypes of BC cells. The effect of varied SATB2-AS1 and miR-155-3p on BC cells in vivo was observed. Dual luciferase reporter gene assay and RNA-pull down assay were implemented to detect the targeting relationship of SATB2-AS1, miR-155-3p, and BRMS1L. Results: SATB2-AS1 and BRMS1L were decreased while miR-155-3p was increased in BC cells and tissues. Patients with lower SATB2-AS1 expression had poor prognosis. Elevated SATB2-AS1 and inhibited miR-155-3p were able to restrain malignant behaviors of BC cells in vitro, as well as decelerate tumor growth in vivo. Oppositely, inhibited SATB2-AS1 and amplified miR-155-3p had converse effects on BC cell growth. MiR-155-3p mimic abrogated the impact of overexpressed SATB2-AS1. SATB2-AS1 could sponge miR-155-3p, and BRMS1L was the target gene of miR-155-3p. Conclusion: Elevated SATB2-AS1 and inhibited miR-155-3p could suppress the malignant phenotypes of BC cells, thereby restricting the development of BC.