Background: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links.Methods: Tissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics.Results: Our FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system.Conclusions: The lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.

Background: The centromere protein O (CENPO) is an important member of the centromere protein family. However, the role of CENPO in pan–cancer and immune infiltration has not been reported. Here, we investigated the role of CENPO in pan–cancer and further validated its role in lung adenocarcinoma (LUAD) by in vitro experiments. Method: The UCSC Xena database and The Cancer Genome Atlas (TCGA)–LUAD data were used to assess the expression levels of CENPO. The potential value of CENPO as a diagnostic and prognostic biomarker for pan–cancer was evaluated using TCGA data and the GEPIA database. The -expression profiles of LUAD patients and the corresponding clinical data were downloaded for correlation analysis. The role of CENPO in immune infiltration was investigated using the UCSC Xena database. Subsequently, qRT–PCR was performed to detect the expression of CENPO. Cell proliferation, migration, and invasion were determined using CCK–8, wound–healing assay, and transwell assay, respectively. Results: CENPO is highly expressed in most cancers, and the upregulation of CENPO is associated with poor prognosis in many cancers. CENPO expression correlates with age, TNM stage, N stage, T stage, and receipt of radiotherapy in LUAD patients, and LUAD patients with high CENPO expression have poorer overall survival (OS) and disease–free survival (DFS). In addition, CENPO expression is associated with immune cell infiltration and immune checkpoint inhibitors. Moreover, the expression of CENPO was closely related to the expression of tumor mutational load and microsatellite instability. In vitro experiments showed that CENPO expression was increased in LUAD cell lines and that knockdown of CENPO significantly inhibited the proliferation, cell invasion, and migration ability of LUAD cells. Conclusion: CENPO may be a potential pan–cancer biomarker and oncogene, especially in LUAD. In addition, CENPO is associated with immune cell infiltration and may serve as a new molecular therapeutic target and effective prognostic marker for LUAD.

Human umbilical cord mesenchymal stem cells (UC-MSCs) are one of the most extensively researched stem cell types due to their potential for multi-lineage differentiation, secretion of regenerative factors, modulations of immunological activities, and the release of regenerative substances and influence immunological processes. Since UC-MSCs must be cultivated on a large scale for clinical use, selecting the appropriate storing passage, such as the usage-based passage of UC-MSCs, is critical for long-term autologous or allogeneic usage. Long-term cultivation of stem cells, on the other hand, causes them to lose their pluripotent differentiation capacity. As a result, distinguishing between high and low passages of UC-MSCs and identifying the particular variations associated with stem cells and their modes of action is essential for regenerative medicine. Therefore, we investigated the biological features and transcriptional changes of UC-MSCs over passages. UC-MSCs were isolated from the tissues of the human umbilical cord, and UC-MSCs from five passages (P1, P3, P5, P10 and P15) with three repetitions were compared and identified based on morphology, cell markers, differentiation capacity, and aging-related characteristics. It was previously assumed that the phenotype of cells before the P10 passage was stable, defined as early passage, and that culture could be continued until the 15th passage, defined as late passage. Next, the five passages of UC-MSCs were sequenced using high-throughput complete transcriptome sequencing. Fuzzy C-Means Clustering (FCM) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to find hub genes, and gene silencing was performed to investigate the impact of missing genes on the stemness of UC-MSC cells. UC-MSCs of different passages displayed similar surface markers, including CD73, CD105, CD90, CD34, CD45 and HLA-DR. However, the proliferation time of late-phase UC-MSCs was longer than that of early-phase UC-MSCs, and the expression of the senescence-associated (SA)-β-gal staining marker was higher. At the same time, pluripotency markers (NANOG, OCT4, SOX2 and KIF4A) were down-regulated, and the multi-differentiation potential was reduced. Meanwhile, KIFC1 and UBE2C were down-regulated in late-phase UC-MSCs, which were involved in the maintenance of stemness. KIFC1 and UBE2C were highly expressed in early-UC-MSCs and showed a downward gradient trend with cell expansion in vitro. They regulated UC-MSC proliferation, colony sphere formation, multiple differentiation, stemness maintenance, and other biological manifestations. Therefore, they are anticipated to be new biomarkers for UC-MSCs quality identification in regenerative medicine applications.

Background The centromere protein O (CENPO) is an important member of the centromere protein family. However, the role of CENPO in pan–cancer and immune infiltration has not been reported. Here, we investigated the role of CENPO in pan–cancer and further validated its role in lung adenocarcinoma (LUAD) by in vitro experiments. Method The UCSC Xena database and The Cancer Genome Atlas (TCGA)–LUAD data were used to assess the mRNA expression levels of CENPO. The potential value of CENPO as a diagnostic and prognostic biomarker for pan–cancer was evaluated using TCGA data and the GEPIA database. The mRNA expression profiles of LUAD patients and the corresponding clinical data were downloaded for correlation analysis. The role of CENPO in immune infiltration was investigated using the UCSC Xena database. Subsequently, RT–QPCR was performed to detect the expression of CENPO. Cell proliferation, migration, and invasion were determined using CCK–8, wound–healing assay, and transwell assay, respectively. Results CENPO is highly expressed in most cancers, and the upregulation of CENPO is associated with poor prognosis in many cancers. CENPO expression correlates with age, TNM stage, N stage, T stage, and receipt of radiotherapy in LUAD patients, and LUAD patients with high CENPO expression have poorer overall survival (OS) and disease–free survival (DFS). In addition, CENPO expression is associated with immune cell infiltration and immune checkpoint inhibitors. Moreover, the expression of CENPO was closely related to the expression of tumor mutational load and microsatellite instability. In vitro experiments showed that CENPO expression was increased in LUAD cell lines and that knockdown of CENPO significantly inhibited the proliferation, cell invasion, and migration ability of LUAD cells. Conclusion CENPO may be a potential pan–cancer biomarker and oncogene, especially in LUAD. In addition, CENPO is associated with immune cell infiltration and may serve as a new molecular therapeutic target and effective prognostic marker for LUAD.