Senescence-associated lncRNAs indicate distinct molecular subtypes associated with prognosis and androgen response in patients with prostate cancer

Cellular senescence has been considered as a hallmark of aging. In this study, we aimed to establish two novel prognostic subtypes for prostate cancer patients using senescence-related lncRNAs. Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Using SNHG1, MIAT and SNHG3, 430 patients in TCGA database were classified into two subtypes associated with biochemical recurrence (BCR)-free survival and subtype 2 was prone to BCR (HR: 19.62, p < 0.001). The similar results were observed in the GSE46602 and GSE116918. For hallmark gene set enrichment, we found that protein secretion and androgen response were highly enriched in subtype 1 and G2M checkpoint was highly enriched in subtype 2. For tumor heterogeneity and stemness, homologous recombination deficiency and tumor mutation burden were significantly higher in subtype 2 than subtype 1. The top ten genes between subtype 2 and subtype 1 were CUBN, DNAH9, PTCHD4, NOD1, ARFGEF1, HRAS, PYHIN1, ARHGEF2, MYOM1 and ITGB6 with statistical significance. In terms of immune checkpoints, only CD47 was significantly higher in subtype 1 than that in subtype 2. For the overall assessment, no significant difference was detected between two subtypes, while B cells score was significantly higher in subtype 1 than subtype 2. Overall, we found two distinct subtypes closely associated with BCR-free survival and androgen response for prostate cancer. These subtypes might facilitate future research in the field of prostate cancer

Interactions between oxidative stress and senescence in cancer: Mechanisms, therapeutic implications, and future perspectives

BACKGROUND: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved. AIM: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects. METHODS: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP. CONCLUSION: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area

Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy

Abstract Background Cellular senescence is growing in popularity in cancer. A dual function is played by the senescence-associated secretory phenotype (SASP) that senescent cells produce in the development of pro-inflammatory niches, tissue regeneration or destruction, senescence propagation, and malignant transformation. In this study, we conducted thorough bioinformatic analysis and meta-analysis to discover detrimental and beneficial subtypes and prognostic index for prostate cancer (PCa) patients using the experimentally confirmed SASP genes. Methods We identified differentially expressed and prognosis-related SASP genes and used them to construct two molecular subtypes and risk score. Another two external cohorts were used to confirm the prognostic effect of the above subtypes and risk score and meta-analysis was further conducted. Additionally, functional analysis, tumor stemness and heterogeneity and tumor microenvironment were also evaluated. We completed analyses using software R 3.6.3 and its suitable packages. Meta-analysis was performed by software Stata 14.0. Results Through multivariate Cox regression analysis and consensus clustering analysis, we used VGF, IGFBP3 and ANG to establish detrimental and beneficial subtypes in the TCGA cohort, which was validated through other two independent cohorts. Meta-analysis showed that detrimental SASP group had significantly higher risk of biochemical recurrence (BCR) than beneficial SASP group (HR: 2.48). Moreover, we also constructed and validated risk score based on these genes to better guide clinical practice. DNA repair, MYC target, oxidative phosphorylation, proteasome and ribosome were highly enriched in detrimental SASP group. Detrimental SASP group had significantly higher levels of B cells, CD8+ T cells, homologous recombination deficiency, loss of heterozygosity, microsatellite instability, purity, tumor mutation burden, mRNAsi, differentially methylated probes and epigenetically regulated RNA expression than beneficial SASP group. The top mutation genes between detrimental and beneficial SASP groups were SPOP, FOXA1, KMT2C, APC, BSN, DNAH17, MYH6, EPPK1, ZNF536 and ZC3H13 with statistical significance. Conclusions From perspective of SASP, we found detrimental and beneficial tumor subtypes which were closely associated with BCR-free survival for PCa patients, which might be important for the furture research in the field of PCa

Membrane tension-mediated stiff and soft tumor subtypes closely associated with prognosis for prostate cancer patients

Abstract Background Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension. Methods Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Results We constructed stiff and soft tumor subtypes using eight membrane tension-related genes through lasso regression and nonnegative matrix factorization analyses. We found that patients in stiff subtype were more prone to biochemical recurrence than those in soft subtype (HR 16.18; p < 0.001), which was externally validated in other three cohorts. The top ten mutation genes between stiff and soft subtypes were DNAH, NYNRIN, PTCHD4, WNK1, ARFGEF1, HRAS, ARHGEF2, MYOM1, ITGB6 and CPS1. E2F targets, base excision repair and notch signaling pathway were highly enriched in stiff subtype. Stiff subtype had significantly higher TMB and T cells follicular helper levels than soft subtype, as well as CTLA4, CD276, CD47 and TNFRSF25. Conclusions From the perspective of cell membrane tension, we found that stiff and soft tumor subtypes were closely associated with BCR-free survival for PCa patients, which might be important for the future research in the field of PCa

Intracellular presence of Helicobacter pylori antigen and genes within gastric and vaginal Candida.

BackgroundHelicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is reported that H. pylori can be internalized into Candida, but more evidence is needed for the internalization of H. pylori in human gastrointestinal Candida and vaginal Candida.MethodsCandida was isolated from vaginal discharge and gastric mucosa biopsies. We PCR-amplified and sequenced H. pylori-specific genes from Candida genomic DNA. Using optical and immunofluorescence microscopy, we identified and observed bacteria-like bodies (BLBs) in Candida isolates and subcultures. Intracellular H. pylori antigen were detected by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled anti-H. pylori IgG antibodies. Urease activity in H. pylori internalized by Candida was detected by inoculating with urea-based Sabouraud dextrose agar, which changed the agar color from yellow to pink, indicating urease activity.ResultsA total of 59 vaginal Candida and two gastric Candida strains were isolated from vaginal discharge and gastric mucosa. Twenty-three isolates were positive for H. pylori 16S rDNA, 12 were positive for cagA and 21 were positive for ureA. The BLBs could be observed in Candida cells, which were positive for H. pylori 16S rDNA, and were viable determined by the LIVE/DEAD BacLight Bacterial Viability kit. Fluorescein isothiocyanate (FITC)-conjugated antibodies could be reacted specifically with H. pylori antigen inside Candida cells by immunofluorescence. Finally, H. pylori-positive Candida remained positive for H. pylori 16S rDNA even after ten subcultures. Urease activity of H. pylori internalized by Candida was positive.ConclusionIn the form of BLBs, H. pylori can internalize into gastric Candida and even vaginal Candida, which might have great significance in its transmission and pathogenicity

Additional file 1 of A pan-cancer analysis of the oncogenic role of leucine zipper protein 2 in human cancer

Additional file 1: Figure S1. The pan-cancer analysis of clinical correlation with LUZP2 expression. Differential expression and prognosis analysis of LUZP2. Figure S2. The pan-cancer Spearman analysis of tumor stemness and LUZP2 expression. Figure S3. The pan-cancer Spearman analysis of tumor heterogeneity and LUZP2 expression. Figure S4. Mutation landscapes analysis of LUZP2 and RNA modification. Figure S5. Tumor immune environment and its correlation with LUZP2 methylatio

. An analysis of the <i>H</i>. <i>pylori</i> 16S rRNA gene sequences produced a neighbor-joining tree.

This phylogenetic tree was constructed using the GenBank reference sequence (H. pylori SS1) and H. pylori 16S rRNA sequences obtained from Candida. SS1 is a standard strain of Helicobacter pylori. V1-V9 and OR226730 represent sequences of H. pylori 16S rRNA genes from vaginal Candida. ON545841, ON545842 and OQ259931 represent sequences of H. pylori 16S rRNA genes from gastric Candida.</p

Immunolabeling of <i>H</i>. <i>pylori</i>.

Immunofluorescence micrographs showing: (a) absence of fluorescence in the C. albicans ATCC 10231 (negative control); (b) presence of fluorescence emitted by H. pylori 26695 strain (positive control); (c) presence of fluorescence emitted by H. pylori (white arrows) inside Candida (magnification × 1000).</p