Assessment of multiple pathways involved in the inhibitory effect of HCG22 on oral squamous cell carcinoma progression.

LncRNAs have been proposed to be associated with the tumorigenesis and progression of oral squamous cell carcinoma (OSCC). LncRNA HLA complex group 22 (HCG22) was reported to be lowly expressed and associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). However, the biological role and related mechanism of HCG22 in OSCC have not been characterized. HCG22 expression in OSCC cells was detected by qRT-PCR. Cell proliferation, invasion, and apoptosis were evaluated by Bromodeoxyuridine (BrdU) proliferation assay, Transwell invasion assay, and flow cytometry analysis, respectively. The protein levels of proliferating cell nuclear antigen (PCNA), E-cadherin, Vimentin, Bcl-2, Bax, protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), and ß-catenin were detected by western blot. Cell growth evaluation was performed using in vitro colony formation assay and in vivo tumor xenograft assay. We found that HCG22 was weakly expressed in OSCC cells. HCG22 overexpression inhibited cell proliferation and invasion and induced apoptosis in OSCC cells. The levels of PCNA, Vimentin, and Bcl-2 were decreased and E-cadherin and Bax expression was elevated in OSCC cells after HCG22 overexpression. Additionally, HCG22 overexpression inhibited the Akt, mTOR and Wnt/ß-catenin pathways. Activation of Akt, mTOR, and Wnt/ß-catenin pathways attenuated the anti-tumor property of HCG22 in OSCC cells. Furthermore, HCG22 overexpression inhibited the growth of OSCC cells in vitro and in vivo. In conclusion, HCG22 exerted anti-tumor property in OSCC by inhibiting the Akt, mTOR, and Wnt/ß-catenin pathways.

Pan-cancer multi-omics analysis and orthogonal experimental assessment of epigenetic driver genes.

The recent identification of recurrently mutated epigenetic regulator genes (ERGs) supports their critical role in tumorigenesis. We conducted a pan-cancer analysis integrating (epi)genome, transcriptome, and DNA methylome alterations in a curated list of 426 ERGs across 33 cancer types, comprising 10,845 tumor and 730 normal tissues. We found that, in addition to mutations, copy number alterations in ERGs were more frequent than previously anticipated and tightly linked to expression aberrations. Novel bioinformatics approaches, integrating the strengths of various driver prediction and multi-omics algorithms, and an orthogonal in vitro screen (CRISPR-Cas9) targeting all ERGs revealed genes with driver roles within and across malignancies and shared driver mechanisms operating across multiple cancer types and hallmarks. This is the largest and most comprehensive analysis thus far; it is also the first experimental effort to specifically identify ERG drivers (epidrivers) and characterize their deregulation and functional impact in oncogenic processes.

Risk factors for aggressive recurrent respiratory papillomatosis in Chinese juvenile patients.

Background: Aggressive juvenile-onset recurrent respiratory papillomatosis (JORRP) threatens patient lives if not receives immediate surgical intervene. Even with surgical intervene, complete remission of this disease is not approachable. Therefore, understanding the factors relevant to disease severity and prognosis will do help to the treatment strategy and health management of this disease.Objective: This study aimed to explore the clinic, laboratory and socioeconomic characteristics of patients and evaluate the risk factors for aggressive JORRP.Methods: The information of clinical and socioeconomic status of the patients was reviewed and its association with disease severity was analyzed. Papilloma from JORRP patients undergone surgeries was used to determine HPV subtypes by real-time PCR. The profiles of mRNA expression in the papilloma were assessed using microarray.Results: Age at diagnosis and socioeconomic status were shown to associate with the severity of JORRP. There was no differential severity considering different HPV subtype. The mRNA expression of nucleotide binding oligomerization domain receptor protein 3 (NLRP3) and Gasdermin B (GSDMB) was reduced in papillomas.Conclusions: A younger age at diagnosis and low socioeconomic status were associated with the severity of JORRP. mRNA expression of NLRP3 and GSDMB in the papillomas of JORRP patients was significantly reduced.Abbreviation: JORRP: Juvenile-onset recurrent respiratory papillomatosis; RRP: Recurrent respiratory papillomatosis; OSAS: Obstructive sleep apnea syndrome; NLRP3: Nucleotide binding oligomerization domain receptor protein 3; GSDMB: Gasdermin B.

A cloud-based workflow to quantify transcript-expression levels in public cancer compendia.

Public compendia of sequencing data are now measured in petabytes. Accordingly, it is infeasible for researchers to transfer these data to local computers. Recently, the National Cancer Institute began exploring opportunities to work with molecular data in cloud-computing environments. With this approach, it becomes possible for scientists to take their tools to the data and thereby avoid large data transfers. It also becomes feasible to scale computing resources to the needs of a given analysis. We quantified transcript-expression levels for 12,307 RNA-Sequencing samples from the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas. We used two cloud-based configurations and examined the performance and cost profiles of each configuration. Using preemptible virtual machines, we processed the samples for as little as $0.09 (USD) per sample. As the samples were processed, we collected performance metrics, which helped us track the duration of each processing step and quantified computational resources used at different stages of sample processing. Although the computational demands of reference alignment and expression quantification have decreased considerably, there remains a critical need for researchers to optimize preprocessing steps. We have stored the software, scripts, and processed data in a publicly accessible repository (https://osf.io/gqrz9).

Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors.

BACKGROUND: Invasive lobular carcinoma (ILC) comprises approximately ~10-20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC. METHODS: We characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue. RNA and DNA were extracted from 3x1.5 mm cores from all foci. Gene expression (730 genes) and copy number (80 genes) were measured using Nanostring PanCancer and Cancer CNV panels. Linear mixed models were employed to compare expression in tumor versus normal samples from the same patient, and to assess heterogeneity (variability) in expression among multiple ILC within an individual. RESULTS: 35 and 34 genes were upregulated (FC>2) and down-regulated (FC<0.5) respectively in ILC tumor relative to adjacent normal tissue, q<0.05. 9/34 down-regulated genes (FIGF, RELN, PROM1, SFRP1, MMP7, NTRK2, LAMB3, SPRY2, KIT) had changes larger than CDH1, a hallmark of ILC. Copy number changes in these patients were relatively few but consistent across foci within each patient. Amplification of three genes (CCND1, FADD, ORAOV1) at 11q13.3 was present in 2/11 patients in both foci. We observed significant evidence of within-patient between-foci variability (heterogeneity) in gene expression for 466 genes (p<0.05 with FDR 8%), including CDH1, FIGF, RELN, SFRP1, MMP7, NTRK2, LAMB3, SPRY2 and KIT. CONCLUSIONS: There was substantial variation in gene expression between ILC foci within patients, including known markers of ILC, suggesting an additional level of complexity that should be addressed.

Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma.

As almost all patients with high-risk neuroblastomas have autograft, we aimed to determine if minimal residual disease (MRD) quantified by RT-PCR for tyrosine hydroxylase in PBSC is prognostic in neuroblastomas. PBSC harvests from 38 children were analyzed. Seven had harvests positive for TH-mRNA. Patients with a positive MRD had a lower 2-year-overall-survival compared to those with negative MRD (P = 0.04) regardless of whether or not PBSC were re-infused. Patients in CR/VGPR group with positive MRD have hazard ratio of death at 7.3 [1.3-40.5]. In conclusion, molecular MRD status in PBSC of good response group may be of interest as a survival prognostic factor in high-risk neuroblastomas.

Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer.

Measurement of telomerase activity is a promising diagnostic tool for pancreatic cancer. Detection of mRNA for human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is also a diagnostic candidate. In the present study, we developed a telomeric repeat amplification protocol assay with real-time PCR and a protocol for quantification of hTERT mRNA with real-time PCR. To evaluate the feasibility of these methods for diagnosis of pancreatic cancer, we measured telomerase activity and hTERT expression in pancreatic cancer cell lines, pancreatic tissues, and pancreatic juice samples from patients with different pancreatic diseases. There were significant correlations between telomerase activity and hTERT expression in cell lines, tissues, and juice samples. The levels of telomerase activity and hTERT expression were significantly higher in tumoral tissues than in nontumoral tissues. In pancreatic juice specimens, some carcinoma samples showed remarkably high expression of hTERT. However, there were no significant differences in hTERT expression between patients with carcinoma and those with benign diseases, although significant differences in telomerase activity were observed. Our present results suggest that the combined assessment of hTERT and telomerase activities in pancreatic juice provides a potent diagnostic method for pancreatic cancer.

[Quantitative assessment of the degree of stomach cancer cell morphologic dedifferentiation]. / Kolichestvennaia otsenka stepeni morfologicheskoi dedifferentsirovki kletok raka zheludka.

Quantitative estimation of the nucleic acids content in the preparations stained with gallocianine-chromic alum was made in 20 cases of stomach cancer. Coefficients of the ratio of the nucleus section surface and the cytoplasm, the ratio of DNA + RNA of the nucleus to RNA of the cytoplasm, and of DNA of the nucleus to the sum total quantity of RNA in the nucleus and the cytoplasm, the index of DNA accumulation were compared in adenocarcinomas (210 cells) and undifferentiated cancers (390 cells) of the stomach. The ratio of the nucleus surface and the cytoplasm, DNA + RNA of the nucleus to RNA of the cytoplasm was higher (statistically significant value) in adenocarcinomas as compared with undifferentiated cancers of the stomach. This allows to suggest a lower differentiation of adenocarcinoma cells in comparison with tumour cells of undifferentiated forms of stomach cancer.