TMC5 is Highly Expressed in Human Cancers and Corelates to Prognosis and Immune Cell Infiltration: A Comprehensive Bioinformatics Analysis

Background: The oncological role of TMC5 in human cancers has only been revealed partially. We performed integrated bioinformatics analysis to provide a thorough and detailed insight of associations between TMC5 and tumorigenesis, cancer progression, and prognosis.Methods: With reference to the accessible online databases, the TMC5 expressions in tumor tissues and corresponding normal tissues, different pathological stages, and various cancer cells were analyzed, while the protein levels of TMC5 in different cancers were also inspected. Meanwhile, the prognostic value of TMC5 expression in multiple cancers as well as in advanced-stage patients was investigated. Furthermore, the mutational data of TMC5 and its correlation with cancer prognosis were assessed. Moreover, the association between the TMC5 level and immune cell infiltration was evaluated. Next, TMC5-related pathway alterations and drug responses were summarized. Finally, the TMC5 based protein network was generated, and relevant enrichment was performed.Results: In our study, the expression level of TMC5 was significantly higher in the tumor tissue than that of the normal tissues in most cancer types. Fluctuations of TMC5 levels were also observed among different pathological stages. In the meantime, the protein level elevated in the tumor tissue in the cancers enrolled. Moreover, the expression of TMC5 was not only prognostic for overall survival (OS) or recurrence free survival (RFS) in various types of cancers but also correlated to OS in patients with more advanced cancers. Additionally, the mutational status of TMC5 is also associated with prognosis in cancer patients. It is worth noting that the TMC5 level was closely related to immune cell infiltrations, especially in ESCA, TGCT, and USC. The TMC5 expression was also identified as an activator for pathways including PI3K/AKT, RAS/MAPK, and TSC/mTOR, proved to be associated with multiple drug responses and assessed to be interactive with the TMEM family.Conclusion: TMC5 might function as a potential marker for cancer survival and immune responses.

NMR-Based Metabolomic Analysis of Sera in Mouse Models of CVB3-Induced Viral Myocarditis and Dilated Cardiomyopathy

Viral myocarditis (VMC) is an inflammatory heart condition which can induce dilated cardiomyopathy (DCM). However, molecular mechanisms underlying the progression of VMC into DCM remain exclusive. Here, we established mouse models of VMC and DCM by infecting male BALB/c mice with Coxsackievirus B3 (CVB3), and performed NMR-based metabonomic analyses of mouse sera. The mouse models covered three pathological stages including: acute VMC (aVMC), chronic VMC (cVMC) and DCM. We recorded 1D 1H-NMR spectra on serum samples and conducted multivariate statistical analysis on the NMR data. We found that metabolic profiles of these three pathological stages were distinct from their normal controls (CON), and identified significant metabolites primarily responsible for the metabolic distinctions. We identified significantly disturbed metabolic pathways in the aVMC, cVMC and DCM stages relative to CON, including: taurine and hypotaurine metabolism; pyruvate metabolism; glycine, serine and threonine metabolism; glycerolipid metabolism. Additionally, we identified potential biomarkers for discriminating a VMC, cVMC and DCM from CON including: taurine, valine and acetate for aVMC; glycerol, valine and leucine for cVMC; citrate, glycine and isoleucine for DCM. This work lays the basis for mechanistically understanding the progression from acute VMC to DCM, and is beneficial to exploitation of potential biomarkers for prognosis and diagnosis of heart diseases.

The Abnormal Metabolites in Tongue Coating of Chronic Gastritis Patients Reflect the Changes in Indexes of Gastroscopic Observation and Gastric Mucosal Pathology

ObjectiveIn this study, we analyzed the correlation between different metabolites in the tongue coating of patients with chronic gastritis, gastroscopy and pathological indexes, and discussed the metabolic mechanism at different pathological stages in the development of chronic gastritis.MethodsWe used GC-TOF-MS and UHPLC-QE-MS metabonomics to detect the distribution of metabolites in the tongue coating of patients with chronic gastritis, and analyzed the correlation between different metabolites in the tongue coating of patients with chronic gastritis and gastroscopy and pathological indexes.ResultsCompared with 50 healthy people, 54 metabolites were upregulated and 47 metabolites were downregulated in 350 patients with chronic gastritis. The main differential metabolites were Lipids and lipid-like molecules, which contain 47 metabolites. The best diagnostic model was composed of 5 metabolites, with an accuracy of 95.4%, a specificity of 87.4% and a sensitivity of 88.0%. These 5 metabolites were 1-methyladenosine, Sphinganine 1-phosphate, 3-Hydroxycapric acid, 4-Ipomeanol, and Nervonic acid. Compared with healthy people, Sphinganine 1-phosphate, 4-Ipomeanol, and Nervonic acid were significantly upregulated in chronic gastritis patients, and 1-methyladenosine and 3-Hydroxycapric acid were significantly downregulated in chronic gastritis patients. After correlation analysis between differential metabolites in tongue coatings and gastroscopic indexes, we found that Trimethylaminoacetone, Sphinganine1-phosphate, alpha-Carboxy-delta-decalactone, and 5,6-Dihydroxyindole were positively correlated with intestinal metaplasia. Conduritol-beta-expoxide, Tetracosanoic acid, Lactosylceramide(d18:1/26:0), Chondrillasterol 3-[glucosyl-(1->4)-glucoside], Azelaic acid, and 1-Methyladenosine were negatively correlated with intestinal metaplasia. Sphinganine1-phosphate, alpha-Carboxy-delta-decalactone, and 5,6-Dihydroxyindole were positively correlated with atrophic. Octadecanol, conduritol-beta-expoxide, Tetracosanoic acid, Smilanippin A, Lactosylceramide(d18:1/26:0), Chondrillasterol 3-[glucosyl-(1->4)-glucoside], and Azelaic acid were negatively correlated with atrophic. 6-deoxyglucitol was negatively correlated with bile reflux, methylmaleic acid, 4-methylcatechol, and 2,4-dichloro-1-(2-chloroethenyl)-benzene were negatively correlated with Hp, 3-benzoyloxy-11-oxo-12-ursen-28-oic acid was negatively correlated with gastric mucosal erosion. From the change trend of different metabolites in different pathological stages, we found that the content of conduritol-beta-expoxide decreased significantly in mild atrophic compared with moderate atrophic and the content of conduritol-beta-expoxide decreased significantly in mild intestinal metaplasia compared with moderate intestinal metaplasia.ConclusionsWe found that Lipids and lipid-like molecules were the main abnormal metabolites in patients with chronic gastritis. Among them, Sphinganine 1-phosphate, which was significantly positively correlated with the aggravation of atrophic and intestinal metaplasia, could be used as one of the diagnostic model markers for chronic gastritis. Additionally, the amount of conduritol-beta-expoxide significantly decreased with the aggravation of atrophic and intestinal metaplasia. We believe that these differential markers in tongue coating may help us to establish a noninvasive and convenient auxiliary detection method for gastritis and gastric precancerous lesion in the future.

Tumor cell invasion in blood vessels assessed by immunohistochemistry is related to decreased survival in patients with bladder cancer treated with radical cystectomy

Background Lymphovascular invasion (VI) is an established prognostic marker for many cancers including bladder cancer. There is a paucity of data regarding whether the prognostic significance of lymphatic invasion (LVI) differs from blood vessel invasion (BVI). The aim was to examine LVI and BVI separately using immunohistochemistry (IHC), and investigate their associations with clinicopathological characteristics and prognosis. A secondary aim was to compare the use of IHC with assessing VI on standard HAS (hematoxylin-azophloxine-saffron) sections without IHC. Methods A retrospective, population –based series of 292 invasive bladder cancers treated with radical cystectomy (RC) with curative intent at Vestfold Hospital Trust, Norway were reviewed. Traditional histopathological markers and VI based on HAS sections were recorded. Dual staining using D2–40/CD31 antibodies was performed on one selected tumor block for each case. Results The frequency of LVI and BVI was 32 and 28%, respectively. BVI was associated with features such as higher pathological stages, positive regional lymph nodes, bladder neck involvement and metastatic disease whereas LVI showed weaker or no associations. Both BVI and LVI independently predicted regional lymph node metastases, LVI being the slightly stronger factor. BVI, not LVI predicted higher pathological stages. BVI showed reduced recurrence free (RFS) and disease specific (DSS) survival in uni-and multivariable analyses, whereas LVI did not. On HAS sections, VI was found in 31% of the cases. By IHC, 51% were positive, corresponding to a 64% increased sensitivity in detecting VI. VI assessed without IHC was significantly associated with RFS and DSS in univariable but not multivariable analysis. Conclusions Our findings indicate that BVI is strongly associated with more aggressive tumor features. BVI was an independent prognostic factor in contrast to LVI. Furthermore, IHC increases VI sensitivity compared to HAS.

A new candidate oncogenic lncRNA derived from pseudogene WFDC21P promotes tumor progression in gastric cancer

As oncogenes and tumor suppressor genes, long non-coding RNAs (lncRNAs) regulate the biological behavior of gastric cancer (GC) cells such as proliferation, invasion, and metastasis through various signal pathways. At present, although numerous lncRNAs that significantly influence the development and progression of GC have been identified, a considerable number of them have not been found and studied yet. In this study, we identified a new lncRNA derived from pseudogenes WFDC21P, which have not been reported in any previous GC study. LncRNA WFDC21P was significantly upregulated in GC cells and tissues, and clinically associated with the pathological stages of advanced GC. WFDC21P promoted proliferation and metastasis of GC cells both in vitro and in vivo. LncRNA WFDC21P was directly bound to GTPase Ran and it promoted the activity of the Akt/GSK3β/β-catenin pathway. Forkhead Box P3 (FOXP3), as a transcription factor of WFDC21P, was directly bound to the promoter region and it positively regulated the transcription of WFDC21P. This finding may provide a novel biomarker and therapeutic target for GC.

Imaging findings of prostate tuberculosis by transrectal contrast-enhanced ultrasound and comparison with 2D ultrasound and pathology

Objectives: This study aimed to investigate the contrast-enhanced ultrasound (CEUS) appearances of prostate tuberculosis (PTB) and its correlation with histopathology. Methods: Clinical, transrectal ultrasonography (TRUS) and CEUS data of 12 PTB patients confirmed by pathology were retrospectively analyzed, and compared to the pathological findings to identify the pathological structures corresponding to different image enhancement areas. Results: No specific characteristics could be found for the clinical appearances. Enlarged gland, hypoechoic lesions and calcification due to PTB could be found by TRUS, which were also non-specific. CEUS showed hypo- or non-enhanced lesions with varying size, which were related to different pathological stages of PTB. The incidence rate of non-enhanced lesions was 83.3%. The detection rate of suspected lesion by CEUS was significantly higher than that by TRUS (χ2 = 8.000, p = 0.005). Histopathology showed that the hypoenhanced area consisted of tuberculous granulomas, caseous necrosis and incomplete destruction of the glands, while the non-enhanced area consisted of caseous or liquified necrosis. Conclusion: CEUS could improve the detection rate of PTB lesions, and the diversity of its manifestations was related to different pathological structures. An enlarged, soft gland with non-enhanced on CEUS may provide valuable information for the diagnosis of PTB, but it is not a substitute for biopsy due to the diversity of CEUS findings. Advances in knowledge: When the lesions of prostate gland are unclear in TRUS examination, CEUS is an ideal option for the detection of lesions, which is conducive to targeted guidance of biopsy areas.

Probability of Transition of Normal Esophageal Mucosa and Precancerous Lesion to the Esophageal Cancer

Background: To estimate the transition probabilities of esophageal cancer（EC） and its precancerous lesions by Markov model, which could provide important information for EC screening about choosing reasonable screening and follow-up intervals.Methods: The transition probabilities among pathological stages were estimated by establishing Markov models for the natural history of EC and repeatedly adjusting and calibrating Markov models by comparing the modeled incidence and distributions of pathological stages (alone or combined) with observed data in real-world condition. Results: In one year, the probabilities were 0.024, 0.05, 0.12 for people from health state progressing to mild dysplasia (mD), mild dysplasia (mD) to moderate dysplasia (MD), and moderate dysplasia (MD) to severe dysplasia/carcinoma in situ (SD/CIS), respectively. The age-specific transition probabilities were 0.08~0.18 for severe dysplasia/carcinoma in situ (SD/CIS) progressing to intramucosal carcinoma(IC), 0.4~0.87 for intramucosal carcinoma (IC) to submucosal carcinoma (T1N0M0) (SC), and 0.2~0.85 for submucosal carcinoma (T1N0M0) (SC) to invasive carcinoma (INC). The progression probabilities increased with age and the severity of the disease. Based on the estimated transition probabilities, we predicted the incidence of EC and distributions of its pathological stages. Comparisons between modeled results with observed data confirmed the validation of our transition probabilities.Conclusions: An esophageal cancer transition model in high-risk areas of China has been established with validity. It could be a point of reference for further economic evaluation and policy formulation of esophageal cancer screening.

Integrative Analysis of DNA Methylation and Gene Expression in Skin Cutaneous Melanoma by Bioinformatic Approaches

Skin cutaneous melanoma is the most life-threatening skin cancer. Finding key methylation genes of prognostic value is an under-explored but intriguing field in the research of skin cutaneous melanoma. This work is aimed to identify survival related methylated genes and their specific methylation sites in skin cutaneous melanoma via an integrative analysis with bioinformatic approaches. The original data, including gene methylation and expression files, were downloaded from the Cancer Genome Atlas database. Statistical analysis revealed that skin cutaneous melanoma patients with highly expressed and hypomethylated HHEX had a better outcome than patients with lowly-expressed and hypermethylated HHEX. In addition, fifteen methylation sites of HHEX were identified to be significantly correlated with HHEX expression changes. In various pathological stages, the expression levels of HHEX were different, and exhibited a downward trend from stage Ⅰ to stage Ⅳ. Therefore, we speculate that the driven gene HHEX may play an important role in the survival of skin cutaneous melanoma. This finding provides novel epigenetic molecular clues and potential detection targets for early prediction of the prognosis of skin cutaneous melanoma.

Inhibitor of DNA-binding family regulates the prognosis of ovarian cancer

Aim: The mechanistic role of inhibitor of DNA binding or differentiation (ID) family in ovarian cancer (OC) has remained unclear. Materials & methods: We used the Oncomine, GEPIA, Kaplan–Meier Plotter, cBioPortal, SurvExpress, PROGgene V2, TIMER, and FunRich to evaluate the prognostic value of IDs in patients with OC. Results: the mRNA transcripts of all IDs were markedly downregulated in OC compared with normal tissue. The prognostic value of IDs was also explored within the subtypes, pathological stages, clinical stages and TP53 mutational status. The group with low-risk IDs showed relatively good overall survival (OS) compared with the high-risk group. Conclusion: ID1/3/4 may be exploited as promising prognostic biomarkers and therapeutic targets in OC patients.