Introduction
Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol’s iodine and Pap test are being used as the standard screening/ diagnostic methods.
Methods
This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies.
Results
A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher’s exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman’s rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059–1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008–1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively).
Conclusion
Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.
Tobacco (
Nicotiana tabacum
L.), one of the major crop plants in Tanzania, cropping affects the level of soil fertility, but the reason has not been known. Plant rhizosphere plays an important role in affecting soil fertility through changing microbial composition. We planned a pilot study to understand the changes in microbial composition and soil nutrients in the rhizosphere soils of tobacco in three agro-ecological zone, namely Sikonge, Tabora and Urambo in Tanzania. This study assessed bacteriota composition using 16S rRNA sequencing and soil fertility in the rhizosphere of tobacco plants. The results showed that bacterial diversity in tobacco rhizosphere soils belonged to
Proteobacteria
phyla, associated significantly (
p
< 0.05) with solubilization of insoluble P, K and S. The solubilization of P, K and S in soils facilitates the availability of these nutrients to the tobacco plants (a heavy feeder crop) allows low levels of these nutrients in the soils for the subsequent crop. The
Proteobacteria
phyla also associated with an increase in soil N content through fixation. Therefore, bacteria diversity in tobacco rhizosphere influence solubilities of macronutrients (P, K, S) and quickly up taken by the tobacco plant and reduces their levels in soils, some bacteria involved in fixing N and increases total N in the soil.
Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide, and effective biomarkers are still lacking for early detection and prognosis prediction. Here, based on gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA), 806 long non-coding RNAs (lncRNAs), 122 microRNAs (miRNAs) and 1269 mRNAs associated with CDK1 were identified. The regulatory axis of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT was determined according to the correlation between gene expression and patient prognosis. The abnormal up-regulation of FAM111B/ZWINT in LUAD was related to hypomethylation. Furthermore, immune infiltration analysis suggested FAM111B/ZWINT could affect the development and prognosis of cancer by regulating the LUAD immune microenvironment. EMT feature analysis suggested that FAM111B/ZWINT promoted tumor spread through the EMT process. Functional analysis showed FAM111B/ZWINT was involved in cell cycle events such as DNA replication and chromosome separation. We analyzed the HERB and GSCALite databases to identify potential target medicines that may play a role in the treatment of LUAD. Finally, the expression of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT axis was verified in LUAD cells by RT-qPCR, and these results were consistent with bioinformatics analysis. Overall, we constructed a CDK1-related ceRNA network and revealed the LINC00460/LINC00525-hsa-mir-338-FAM111/ZWINT pathways as potential diagnostic biomarkers or therapeutic targets of LUAD.
Titanium dioxide nanoparticles (TiO2-NPs) are widely used for biomedical and food applications, the toxicity of TiO2-NPs in vivo and in vitro has been elucidated, but the underlying cytotoxicity of TiO2-NPs against microRNA remains largely unknown. The purpose of this study was to analyze microRNA profiling induced by TiO2-NPs against NCM460 and HCT116 cell lines. Comparative analysis identified 34 and 24 microRNAs were significantly altered in the TiO2-NPs treated cells at concentrations of 3 μg/mL and 30 μg/mL, respectively. Functional classification demonstrated that a large proportion of genes involved in metabolism, human disease, and environmental information process were significantly upregulated by TiO2-NPs. Bioinformatics analysis suggested that microRNA 378 might be an early indicator of cellular response to exogenous stimuli with apoptotic signals. Furthermore, TiO2-NPs significantly altered the expression of microRNA 378b and 378g in HCT116 and NCM460 cell lines at different concentrations from 3 to 6 μg/mL. These concentrations elicit high-sensitivity of stimuli response in colon cancer cells when exposed to the slight doses of TiO2-NPs. Our study indicated that microRNAs 378b and 378g may play an important role in TiO2-NPs-mediated colonic cytotoxicity, which may provide a valuable insight into the molecular mechanisms of potential risks in colitis and colon cancer.
Lung adenocarcinoma (LUAD) is one of the most common malignancies, and there is still a lack of effective biomarkers for early detection and prognostic prediction. Here, we comprehensively analyze the characteristics of. an RNA sequencing data set of LUAD samples. In total, 395 long non-coding RNAs (lncRNAs), 89 microRNAs (miRNAs), and 872 mRNAs associated with c-Myc were identified, which were differentially expressed between tumor and normal tissues. The most relevant pathway was found to be WT1-AS–miR-200a-3p–IGF2BP2 according to the rules of competitive endogenous RNA (ceRNA) regulation. WT1-AS and IGF2BP2 expression were positively correlated and increased in LUAD samples, while miR-200a-3p had relatively low expression. The high expression of WT1-AS and IGF2BP2 was associated with poor prognosis in LUAD patients, while low expression of miR-200a-3p predicted reduced survival (p < 0.05). The analysis of the multi-gene regulation model indicated that the WT1-AS (downregulation)–miR-200a-3p (upregulation)–IGF2BP2 (downregulation) pattern significantly improved the survival of LUAD patients. Finally, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were detected in LUAD cells, and the results are consistent with the bioinformatics analysis. In summary, the WT1-AS/IGF2BP2 axis is a potential prognostic biomarker in LUAD and is expected to become an effective target for diagnosis and treatment.
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