Characterizing the genetic alterations leading to the more aggressive forms of estrogen receptor positive (ER+) breast cancers are of critical significance in breast cancer management. Here we identify recurrent rearrangements between estrogen receptor gene ESR1 and its neighbor CCDC170, which are enriched in the more aggressive and endocrine-resistant luminal-B tumors, through large-scale analyses of breast cancer transcriptome and copy number alterations. Further screening of 200 ER+ breast cancers identifies eight ESR1-CCDC170 positive tumors. These fusions encode N-terminally truncated CCDC170 proteins (ΔCCDC170). When introduced into ER+ breast cancer cells, ΔCCDC170 leads to markedly increased cell motility and anchorage-independent growth, reduced endocrine sensitivity, and enhanced xenograft tumor formation. Mechanistic studies suggest that ΔCCDC170 engages Gab1 signalosome to potentiate growth factor signaling and enhance cell motility. Together, this study identifies neoplastic ESR1-CCDC170 fusions in a more aggressive subset of ER+ breast cancer, which suggests a new concept of ER pathobiology in breast cancer.
Surgery as a therapeutic modality for non-small cell lung cancer is widely accepted in clinical practice. However, the role of surgery for small cell lung cancer (SCLC) remains controversial. Therefore, in the present study a period propensity score matching analysis using the Surveillance, Epidemiology and End Results (SEER) Registry database was performed to investigate the role of surgery on survival in patients with SCLC. Patients with SCLC between January 2010 and December 2015 were identified from the SEER database, and individual data for each case regarding general clinical characteristics, surgery of primary site (SPS), cause-specific death classification and survival time were retrieved. Differences of cause-specific survival (CSS) between subgroups were estimated by the log-rank test. Cox regression analysis was used to evaluate the effects of multiple variables on CSS, and differences between the incidences of cause-specific death were examined using a χ2 test. A total of 1,707 records met the inclusion criteria and were retrieved for analysis. There were significant differences of CSS in the clinicopathological features of N (P=0.01), Stage (P<0.01) and Surgery (P<0.01) when comparing non-surgery with surgery, and in N (P<0.001), Stage (P=0.006) and Surgery (P=0.049) when comparing sublobectomy with lobectomy or bilobectomy (lobe/s). Patients who did not receive surgery (P<0.001) or who received sublobectomy (P=0.03) had an increased risk of mortality when compared with patients who received surgery and lobe/s. The findings of the present study indicate that surgery should be taken into consideration when an initial treatment strategy is made in patients for patients with SCLC at clinical stage I–IIA (T1-2,N0,M0), regardless of whether they are >50 years of age, their sex, histology and grade. The results suggest that certain patients with SCLC with stage IIB (N1) can also benefit from lobe/s, although further investigation is required. In addition, lobe/s is preferable to sublobectomy when surgery is performed. However, the present study was unable to comprehensively analyze the efficacy of pneumonectomy for SCLC.
Our findings revealed that the activity of Family_XIII_AD3011_group and Corynebacterium is strongly correlated with the beneficial regulation of physiological hormones and metabolic changes during pregnancy and lactation. These findings are key for guiding targeted microbial therapeutic approaches to modulate microbiomes in gestating and lactating mammals.
The gut microbiota play a vital role in regulating endocrine-mediated metabolism, immunity, and energy metabolism. However, little is known about the gut microbiota and metabolite composition and development throughout pregnancy and lactation. Here, we used amplicon sequencing to analyze the gut microbiota composition of 35 female mice in five stages of pregnancy and lactation, namely, non-receptive (NR) stages, sexually-receptive (SR) stages, at day 15 of pregnancy (Pre_D15), at the day of birth (Del), and at day 10 of lactation (Lac_D10). The results revealed that the α diversity of gut microbiota was significantly increased during pregnancy and lactation. In addition, the principal coordinate analysis (PCoA) conducted on the amplicon sequence variants’ (ASVs’) distribution of the 16S rRNA amplicons indicated that the microbiota composition was significantly different among the five groups. Based on a random forest analysis, Oscillospira, Dehalobacterium, and Alistipes were the most important microbiota. The abundance of Allobaculum, Oscillospira, and Ruminococcus were negatively correlated with the serum progesterone concentration, while the abundance of Oscillospira was positively correlated with the propionate and valerate concentration in the caecal contents. Moreover, the concentration of acetate and propionate in the Del and Lac_D10 stages was significantly lower than in the SR and Pre_D15 stages. Our findings indicate that some gut microbes and metabolites vary considerably at the different stages of pregnancy and during lactation stages, which can potentially be used as microbial biomarkers. These results provide information on the potential use of the identified microbes as probiotics to maintain a healthy pregnancy and lactation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.