Current Genomics - Online First

Lysosomal dysfunction is significantly associated with tumor progression. This study aimed to identify and develop a new predictive panel for breast cancer (BRCA) and examine its relationship with the immune environment and therapeutical status.

We developed a prognostic panel employing lysosomal genes from The Cancer Genome Atlas Program (TCGA) and then validated and assessed it externally in the Gene Expression Omnibus (GEO). Furthermore, the disparities were identified between high and low-risk subgroups by examining the infiltration of microenvironment cells, gene expression of immune checkpoints, and small molecular compounds. Ultimately, the cancerous function and potential pathway of core LRG were verified using a series of in vitro tests.

First, the predictive panel of lysosome-related genes (LRGs) was generated via the least absolute shrinkage and selection operator. High-risk populations showed the shortest survival times. Meanwhile, the area under the curves (AUC) for predicting 1-, 3-, and 5-year survival rates indicated good predictive performance across all cohorts. Subsequent extensive investigations revealed a strong correlation between the risk score and the pathological stage, drug sensitivity, and tumor mutation burden (TMB). Then, we discovered that the levels of GPLD1, PLA2G5, and STX7 were reduced in BRCA tissues, whereas the expressions of PLA2G10, LAMP3, EIF4EBP1, and LPCAT1 were elevated in BRCA tissues compared to paracancerous tissues. Patients exhibiting high EIF4EBP1 expression experienced a more unfavorable outcome compared to those with low expression. EIF4EBP1 disruption dramatically impeded BRCA cell growth and invasive capacity, as demonstrated by CCK8, wound healing, and transwell assays. Moreover, EIF4EBP1 silencing in BRCA cells significantly restricted the TGF-β pathway.

Our 9-LRG panel is a promising classifier for assessing the prognosis of BRCA. Notably, targeting EIF4EBP1 could potentially serve as a theoretical foundation for enhancing the prognosis of BRCA patients.

Phthalic acid esters (PAEs) are widely used chemical compounds in various industries. However, PAEs are also a major source of pollution in soil and aquatic ecosystems, posing a significant environmental threat. Microbial degradation is a very effective way to remove phthalic acid esters from a polluted environment.

The aims of this study were to investigate the ability of the strain Arthrobacter sp. SF27 (=VKM Ac-2063) to degrade PAEs (specifically, dibutyl phthalate (DBF)); to annotate the complete genome of the strain SF27 (GenBank accession number GCA_012952295); to identify genes (gene clusters) potentially involved in the degradation of DBF and its major degradation product, phthalic acid (PA).

The ability of the strain SF27 to use DBP as the only source of carbon and energy was determined by cultivating it on a mineral medium containing 0.5–4 g/L DBP. The evaluation of the bacterial decomposition of DBP was carried out by GC-MS. The genome was annotated using the JGI Microbial Genome Annotation Pipeline (MGAP) (https://jgi.doe.gov/). Functional annotation was performed using various databases: KEGG, COG, NCBI, and GO. The Mauve program was used to compare the strain SF27 genome and the genomes of the closest DBP-degrading strains.

The strain Arthrobacter sp. SF27 is capable of growing on DBP as the sole source of carbon and energy at high concentrations (up to 4 g/L). The strain was able to degrade 60% of DBP (initial concentration of 1 g/L) and 20% of DBP (initial concentration of 3 g/L) within 72 hours. The genome analysis of the strain SF27 (GenBank accession number GCA_012952295) identified genes encoding hydrolases potentially involved in the initial stages of DBP degradation, leading to the formation of PA. Additionally, a cluster of pht genes encoding enzymes that are responsible for the transformation of PA into protocatechuic acid (PCA) has been identified and described in the genome. Based on genome analysis and cultural experiments, a complete pathway for the degradation of PA by the strain Arthrobacter sp. SF27 into basal metabolic compounds of the cell has been proposed.

Based on the conducted research, it can be stated that the strain Arthrobacter sp. SF27 is an efficient degrader of DBP, promising for the development of biotechnologies aimed at the restoration of ecosystems contaminated with DBP.