Cancer Informatics最新文献

Nuclear paraspeckles are subnuclear bodies contracted by nuclear-enriched abundant transcript 1 (NEAT1) long non-coding RNA, localised in the interchromatin space of mammalian cell nuclei. Paraspeckles have been critically involved in tumour progression, metastasis and chemoresistance. To this date, there are limited findings to suggest that paraspeckles, NEAT1 and heterogeneous nuclear ribonucleoproteins (hnRNPs) directly or indirectly play roles in osteosarcoma progression. Herein, we analysed NEAT1, paraspeckle proteins (SFPQ, PSPC1 and NONO) and hnRNP members (HNRNPK, HNRNPM, HNRNPR and HNRNPD) gene expression in 6 osteosarcoma tumour tissues using the single-cell RNA-sequencing method. The normalised data highlighted that the paraspeckles transcripts were highly abundant in osteoblastic OS cells, except NEAT1, which was highly expressed in myeloid cell 1 and 2 subpopulations.

Head and neck squamous cell carcinoma (HNSC) is a widely known malignancy which is usually diagnosed late and has a poor prognosis. This study focuses on finding a new gene linked with CD8+ T cell infiltration as a prognostic marker for patients with HNSC. Differential analysis of transcriptomic data was performed between HNSC and control tissues from TCGA and GEO database. The CD8+ T cell infiltration score was quantified using single-sample gene set enrichment analysis (ssGSEA). Weighted gene co-expression network analysis (WGCNA) algorithms were used to identify key modules associated with CD8+ T cell infiltration. Kaplan-Meier (K-M) survival analysis was used to compare overall survival (OS) between the 2 groups. Univariate and multivariate Cox analyses were used to assess independent prognostic markers. The results showed CD8+ T cell infiltration score was an independent favorable prognostic marker in HNSC. Differential analysis and WGCNA identified 93 differential gene related to high CD8+ T infiltration. Amog the 93 genes, ALDH2 was an independent favorable prognostic marker in HNSC. ALDH2 expression was found to be much lower in HNSC, and patients with low ALDH2 expression had higher T stage and N stage. The correlation analysis showed that ALDH2 was linked with immune cell infiltration in the tumor microenvironment of HNSC. Patients having increased expression of ALDH2 tend to be sensitive to immune checkpoint inhibitors (ICIs). In addition, we showed the relationship between ALDH2 expression and chemotherapeutic drug sensitivity. In conclusion, this study identified ALDH2 as a prognostic marker, associated with CD8+ T cell infiltration in HNSC.

Proteasome a highly sophisticated systems that alter protein structure and function. Proteasome 26S Subunit, Non-ATPase (PSMD) genes have been implicated in several types of malignancies. This is the first study to look at how proteasomal subunits are expressed in patients with bladder urothelial carcinoma (BLCA). BLCA was used to evaluate the predictive value of PSMD genes (PSMD1 to PSMD12) in relation to clinicopathological characteristics. PSMD genes' expression patterns at the mRNA level were analyzed using a variety of bioinformatics methods, including gene expression profile integrative analysis (GEPIA), Oncomine, TCGA, and Gene expression Omnibus (GEO) databases. The GEPIA and TCGA dataset survival plot functions were used to assess the prognostic significance of PSMD genes. PSMD2, PSMD3, PSMD4, PSMD8, and PSMD11 genes were significantly overexpressed in BLCA compared with normal bladder tissues. PSMD2 and PSMD8 were significantly overexpressed in BLCA more than other types of cancer. High level of PSMD2 and PSMD8 predicted shorter overall (OS) and progression free survival (PFS) in BLCA patients. High level of PSMD2 was significantly associated with elder age (P < .001), female gender (P = .014), tumor grade (P < .001), and metastasis (P = .003). PSMD2 has been shown to be an independent predictor for OS in BLCA patients based on univariate and multivariate analysis (P < .001). Overall, according to this study, PSMD2 and PSMD8 could be served as a prognostic biomarker for BLCA patients.

Background: Despite the fact that cervical cancer is preventable disease, it is the fourth most frequently diagnosed cancer and leading cause of cancer death in women. An estimated 604 000 women were diagnosed with cervical cancer worldwide and 342 000 women died from the disease. Therefore, the purpose of this study was to determine the prevalence and factors associated with cervical cancer among women attended cervical cancer screening center in Gahandi memorial Hospital.

Methods: An institutional-based cross-sectional study was conducted at Gahandi Memorial Hospital in which simple random sampling technique was used to select 422 registration books of women who visited the hospital between May 2015 and May 2019. Texts, tables, and graph were used to present results. Binary logistic regression with a P-value of <.25 and multivariate logistic regression with a P-value of <.05 were used to determine the association between independent variables and outcome variable.

Results: In this study, from the total of 422 women screened with visual inspection with acetic acid (VIA) screening test, 23.5% of them were found to be positive for VIA test. From those who were diagnosed positive with VIA screening test, about 10.1 % were identified with high grade lesions. Having multiple sexual partners (AOR = 1.83, 95% CI: 1.21-3.29), being HIV-positive (AOR = 2.22, 95% CI:1.10-4.69), having a history of Sexual Transmitted Infection (STI) (AOR = 6.76, 95% CI: 1.14-3.90), and beginning sexual intercourse at early age (AOR = 1.38, 95% CI: 1.20-5.13) were factors associated with cervical cancer.

Conclusion: The study concluded that the high prevalence of cervical cancer. Having multiple sexual partners, being Human Immune Deficiency Virus (HIV) positive, having STI history and early initiation of sexual intercourse were factors associated with cervical cancer. Therefore, avoiding multiple sexual partners, delaying of early sexual contact, and self-protection from STI infections might help to prevent cervical cancer.

Background: Colorectal cancer is the third largest cause of cancer-related mortality worldwide. Although current treatments with chemotherapeutics have allowed for management of colorectal cancer, additional novel treatments are essential. Intervening with the metabolic reprogramming observed in cancers called "Warburg Effect," is one of the novel strategies considered to combat cancers. In the metabolic reprogramming pathway, pyruvate dehydrogenase kinase (PDK1) plays a pivotal role. Identification and characterization of a PDK1 inhibitor is of paramount importance. Further, for efficacious treatment of colorectal cancers, combinatorial regimens are essential. To this end, we opted to identify a PDK1 inhibitor using computational structure-based drug design FINDSITE^comb and perform combinatorial studies with 5-FU for efficacious treatment of colorectal cancers.

Methods: Using computational structure-based drug design FINDSITE^comb, stearic acid (SA) was identified as a possible PDK1 inhibitor. Elucidation of the mechanism of action of SA was performed using flow cytometry, clonogenic assays.

Results: When the growth inhibitory potential of SA was tested on colorectal adenocarcinoma (DLD-1) cells, a 50% inhibitory concentration (IC₅₀) of 60 µM was recorded. Moreover, SA inhibited the proliferation potential of DLD-1 cells as shown by the clonogenic assay and there was a sustained response even after withdrawal of the compound. Elucidation of the mechanism of action revealed, that the inhibitory effect of SA was through the programmed cell death pathway. There was increase in the number of apoptotic and multicaspase positive cells. SA also impacted the levels of the cell survival protein Bcl-2. With the aim of achieving improved treatment for colorectal cancer, we opted to combine 5-fluorouracil (5-FU), the currently used drug in the clinic, with SA. Combining SA with 5-FU, revealed a synergistic effect in which the IC₅₀ of 5-FU decreased from 25 to 6 µM upon combination with 60 µM SA. Further, SA did not inhibit non-tumorigenic NIH-3T3 proliferation.

Conclusions: We envision that this significant decrease in the IC₅₀ of 5-FU could translate into less side effects of 5-FU and increase the efficacy of the treatment due to the multifaceted action of SA. The data generated from the current studies on the inhibition of colorectal adenocarcinoma by SA discovered by the use of the computational program as well as synergistic action with 5-FU should open up novel therapeutic options for the management of colorectal adenocarcinomas.