Microfibril Associated Protein 5 (MFAP5) Is Related to Survival of Ovarian Cancer Patients but Not Useful as a Prognostic Biomarker.

Ovarian cancer (OC) is usually diagnosed late due to its nonspecific symptoms and lack of reliable tools for early diagnostics and screening. OC studies concentrate on the search for new biomarkers and therapeutic targets. This study aimed to validate the MFAP5 gene, and its encoded protein, as a potential prognostic biomarker. In our previous study, we found that patients with high-grade serous OC who had higher MFAP5 mRNA levels had shorter survival, as compared with those with lower levels. Here, we used the Kaplan-Meier Plotter and CSIOVDB online tools to analyze possible associations of MFAP5 expression with survival and other clinico-pathological features. In these analyses, higher MFAP5 mRNA expression was observed in the more advanced FIGO stages and high-grade tumors, and was significantly associated with shorter overall and progression-free survival. Next, we analyzed the expression of the MFAP5 protein by immunohistochemistry (IHC) in 108 OC samples and tissue arrays. Stronger MFAP5 expression was associated with stronger desmoplastic reaction and serous vs. non-serous histology. We found no significant correlation between IHC results and survival, although there was a trend toward shorter survival in patients with the highest IHC scores. We searched for co-expressed genes/proteins using cBioPortal and analyzed potential MFAP5 interaction networks with the STRING tool. MFAP5 was shown to interact with many extracellular matrix proteins, and was connected to the Notch signaling pathway. Therefore, although not suitable as a prognostic biomarker for evaluation with a simple diagnostic tool like IHC, MFAP5 is worth further studies as a possible therapeutic target.

The prognostic value of the lysyl oxidase family in ovarian cancer.

BACKGROUND: Our study intended to evaluate the prognostic value of lysyl oxidase (LOX) and its four relevant members, the lysyl oxidase-like genes (LOXL1-4), in ovarian cancer (OC) patients. MATERIAL AND METHODS: The Kaplan-Meier plotter (KM plotter) database was used to investigate the prognostic power of the LOX family for OC patients. Overall survival (OS) and progression-free survival (PFS) were the clinical endpoints. The prognostic roles of the LOX family in OC patients were also analyzed according to various clinicopathological characteristics, including histological subtypes, clinical stages, pathological grades, and chemotherapeutic treatments. RESULTS: Overexpression of LOX, LOXL1, LOXL2, and LOXL3 mRNA indicated poor OS and PFS in OC patients, particularly in serous and grade II + III OC patients. Overexpression of LOXL4 mRNA resulted in worse PFS in OC patients. Overexpression of LOX and LOXL1 mRNA showed worse OS and PFS in stage III + IV OC patients, and overexpression of LOXL3 mRNA indicated worse OS and PFS in stage I + II OC patients. Overexpression of LOX, LOXL3, and LOXL4 mRNA indicated worse OS and PFS among OC patients who received platinum, taxol, and taxol + platinum chemotherapy. Overexpression of LOXL1 and LOXL2 mRNA was related to lower OS and PFS in OC patients who received platinum chemotherapy. CONCLUSION: LOX, LOXL1, LOXL2, and LOXL3 may become potential predictive markers for negative outcomes in OC patients. Moreover, the LOX family can serve as new molecular predictors for the efficiency of platinum-based chemotherapy in OC patients.

Identification of potential miRNA-mRNA regulatory network contributing to pathogenesis of HBV-related HCC.

BACKGROUND: Hepatitis B virus (HBV) is one of the major risk factors of hepatocellular carcinoma (HCC). Increasing evidence indicates that microRNA (miRNA)-mRNA axis is involved in HCC. However, a comprehensive miRNA-mRNA regulatory network in HBV-related HCC is still absent. This study aims to identify potential miRNA-mRNA regulatory pathways contributing to pathogenesis of HBV-related HCC. METHODS: Microarray GSE69580 was downloaded from Gene Expression Omnibus (GEO) database. GEO2R and 'R-limma' were used to conduct differential expression analysis. The common miRNAs appeared in the two analytic sets were screened as potential differentially expressed miRNAs (DE-miRNAs). The prognostic roles of screened DE-miRNAs in HCC were further evaluated using Kaplan-Meier plotter database. Target genes of DE-miRNAs were predicted by miRNet. Then, protein-protein interaction (PPI) networks were established for these targets via the STRING database, after which hub genes in the networks were identified by Cytoscape. Functional annotation and pathway enrichment analyses for the target genes were performed through DAVID database. Three enriched pathways related to HBV-related HCC were selected for further analysis and potential target genes commonly appeared in all three pathways were screened. Cytoscape was employed to construct miRNA-hub gene network. The expression and correlation of potential miRNAs and targets were further detected in clinical HBV-related HCC samples by qRT-PCR. RESULTS: 7 upregulated and 9 downregulated DE-miRNAs were accessed. 5 of 7 upregulated DE-miRNAs and 5 of 7 downregulated DE-miRNAs indicated significant prognostic roles in HCC. 2312 and 1175 target genes were predicted for the upregulated and downregulated DE-miRNAs, respectively. TP53 was identified as the hub gene in the PPI networks. Pathway enrichment analysis suggested that these predicted targets were linked to hepatitis B, pathways in cancer, microRNAs in cancer and viral carcinogenesis. Further analysis of these pathways screened 20 and 16 target genes for upregulated and downregulated DE-miRNAs, respectively. By detecting the expression of 36 target genes, six candidate target genes were identified. Finally, a potential miRNA-mRNA regulatory network was established based on the results of qRT-PCR and expression correlation analysis. CONCLUSIONS: In the study, potential miRNA-mRNA regulatory pathways were identified, exploring the underlying pathogenesis and effective therapy strategy of HBV-related HCC.

Comprehensive analysis of non-small-cell lung cancer microarray datasets identifies several prognostic biomarkers.

Aim: To find accurate and effective biomarkers for diagnosis of non-small-cell lung cancer (NSCLC) patients. Materials & methods: We downloaded microarray datasets GSE19188, GSE33532, GSE101929 and GSE102286 from the database of Gene Expression Omnibus. We screened out differentially expressed genes (DEGs) and miRNAs (DEMs) with GEO2R. We also performed analyses for the enrichment of DEGs' and DEMs' function and pathway by several tools including database for annotation, visualization and integrated discovery, protein-protein interaction and Kaplan-Meier-plotter. Results: Total 913 DEGs were screened out, among which ten hub genes were discovered. All the hub genes were linked to the worsening overall survival of the NSCLC patients. Besides, 98 DEMs were screened out. MiR-9 and miR-520e were the most significantly regulated miRNAs. Conclusion: Our results could provide potential targets for the diagnosis and treatment of NSCLC.

Prognostic values of S100 family members in ovarian cancer patients.

OBJECTIVE: Exhibiting high consistence in sequence and structure, S100 family members are interchangeable in function and they show a wide spectrum of biological processes, including proliferation, apoptosis, migration, inflammation and differentiation and the like. While the prognostic value of each individual S100 in ovarian cancer is still elusive. In current study, we investigated the prognostic value of S100 family members in the ovarian cancer. METHODS: We used the Kaplan Meier plotter (KM plotter) database, in which updated gene expression data and survival information are from 1657 ovarian cancer patients, to assess the relevance of individual S100 family mRNA expression to overall survival in various ovarian cancer subtypes and different clinicopathological features. RESULTS: It was found that high expression of S100A2 (HR = 1.18, 95%CI: 1.04-1.34, P = 0.012), S100A7A (HR = 1.3, 95%CI: 1.04-1.63, P = 0.02),S100A10 (HR = 1.2, 95%CI: 1.05-1.38, P = 0.0087),and S100A16 (HR = 1.23, 95%CI: 1-1.51, P = 0.052) were significantly correlated with worse OS in all ovarian cancer patients, while the expression of S100A1 (HR = 0.87, 95%CI: 0.77-0.99, P = 0.039), S100A3 (HR = 0.83, 95%CI: 0.71-0.96, P = 0.0011), S100A5 (HR = 0.84, 95%CI: 0.73-0.97, P = 0.017), S100A6 (HR = 0.84, 95%CI: 0.72-0.98, P = 0.024), S100A13 (HR = 0.85, 95%CI:0.75-0.97, P = 0.014) and S100G (HR = 0.86, 95%CI: 0.74-0.99, P = 0.041) were associated with better prognosis. Furthermore, we assessed the prognostic value of S100 expression in different subtypes and the clinicopathological features, including pathological grades, clinical stages and TP53 mutation status, of ovarian cancer patients. CONCLUSION: Comprehensive understanding of the S100 family members may have guiding significance for the diagnosis and outcome of ovarian cancer patients.

Distinct prognostic values of YAP1 in gastric cancer.

The Hippo pathway regulates intrinsic organ sizes by regulating apoptosis and cell proliferation. YAP1 (yes-associated protein 1) is a transcriptional effector of the Hippo pathway. YAP1 expression is reported to be associated with gastric cancer carcinogenesis and malignancy. In this study, we compared the expression of YAP1 in gastric cancer and normal stomach tissues. Tissue microarray analysis was performed in 156 gastric cancer samples, 8 adjacent normal stomach tissues, and 4 normal stomach tissues. We also analyzed the association between YAP1 protein expression and clinicopathological features, such as age, gender, histological differentiation, and clinical stages. We used the ONCOMINE database and the Kaplan-Meier plotter to analyze YAP1 expression status in different clinicopathological parameters of gastric cancer. We also used the Kaplan-Meier plotter to summarize the survival information of YAP1 from a total of 631 gastric cancer patients. YAP1 expression was found to be elevated in gastric cancer tissues compared to normal stomach tissues. YAP1 messenger RNA was found to be upregulated in gastric intestinal-type adenocarcinoma and gastric mixed adenocarcinoma compared to gastric mucosa. YAP1 high expression was found to be correlated to worse overall survival for all gastric cancer patients followed for 20 years. These results indicate that YAP1 can be used to predict the prognosis of gastric cancer. And YAP1 maybe a potential drug target for gastric cancer patients.

Integrated bioinformatics analysis of microarray data from the GEO database to identify the candidate genes linked to poor prognosis in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common cancers with high morbidity and mortality and remains a crucial factor endangering human health. OBJECTIVE: This study aimed to elucidate the potential treatment target and prognostic biomarker in patients with LUAD through a comprehensive bioinformatics analysis. METHODS: The three public microarray datasets of GSE118370, GSE116959, and GSE43767 were obtained from the GEO data resource. The DEGs were explored between LUAD and non-malignant samples using GEO2R online tool in GEO data resource. GO along with KEGG analysis of DEGs were examined using WebGestalt tool. The STRING web resource was employed to develop the PPI network of DEGs, whereas Cytoscape software was employed to perform module analysis. Finally, the mRNA, protein expression along with survival analysis of hub genes were explored via GEPIA, HPA along with Kaplan-Meier plotter web resource, respectively. RESULTS: Only 82 upregulated and 105 downregulated DEGs were found among the three datasets. Further, GO analysis illustrated that 187 DEGs were primary enriched in extracellular structure organization, tube development along with cell adhesion. The KEGG enrichments showed that these DEGs were primary linked to leukocyte transendothelial migration, vascular smooth muscle contraction along with ECM-receptor interaction. Among the 187 DEGs, the 10 hub genes (P4HB, SPP1, CP, GOLM1, COL1A1, MMP9, COL10A1, APOA1, COL4A6, and TIMP1) were identified. The mRNA along with protein levels of hub genes in LUAD tissues were further verified by Oncomine, UCSC Xena, GEPIA and HPA databases. Additionally, overall survival curves illustrated that LUAD patients with the higher levels of P4HB, SPP1, COL1A1, and MMP9 were dramatically linked to shorter overall survival. CONCLUSIONS: The current study identified DEGs candidate genes (P4HB, SPP1, COL1A1, and MMP9) and pathways in LUAD using bioinformatics analysis, which could enhance our understanding of pathogenesis along with underlying molecular events in LUAD, and these hub genes and pathways may help provide candidate treatment targets for LUAD.

The role of complement in the clinical course of hepatocellular carcinoma.

BACKGROUND: The complement system, an innate immune system, may either play an antitumor role, or promote tumorigenesis and cancer progression in different kinds of cancer. The function of complement in hepatocellular carcinoma (HCC) is unclear. METHODS: The gene expressions of the complement system were based on data obtained from TCGA and GEO. We explored gene expressions, mutation, enrichment analysis, clinicopathology, patients' outcome, and immune infiltration via Gepia2, cBioPortal, Metascape, UALCAN, Kaplan-Meier Plotter, and TIMER 2. RESULTS: Five complement genes, including C1R, C6, C7, CFP, and CFHR3, were not only found to be significantly downregulated in HCC samples compared with normal liver samples, but also found to be significantly associated with overall survival, disease-free survival, and progress-free survival in HCC patients. In addition, lower mRNA expression of C1R, C6, C7, and CFHR3 were found correlated with advanced cancer stages and higher tumor grades in HCC patients. Also, the expression levels of CFP were correlated with many sets of immune markers of tumor immune cells, such as those of CD8+ T cells, CD4+ T cells, B cells, M2 macrophages, neutrophils, DCs, Th1 cells, Th2 cells, and T cell exhaustion in HCC. Based on that, we developed a prognostic model for HCC patients-Riskscore = (-0.0053)*C6+(-0.0498)*C7+(-0.1045)*CFHR3. CONCLUSION: C1R, C6, C7, CFP, and CFHR3 could be prognostic biomarkers for patients with HCC.

Identification of potential biomarkers for diagnosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate owing to its complexity. Identification of abnormally expressed genes in HCC tissues compared to those in normal liver tissues is a viable strategy for investigating the mechanisms of HCC tumorigenesis and progression as a means of developing novel treatments. A significant advantage of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) is that the data therein were collected from different independent researchers and may be integrated, allowing for a more robust data analysis. Accordingly, in the present study, the gene expression profiles for HCC and control samples were downloaded from the GEO and TCGA. Functional enrichment analysis was performed using a Metascape dataset, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/proteins (STRING) online database. The prognostic value of mRNA for HCC was assessed using the Kaplan-Meier Plotter, a public online tool. A gene mRNA heatmap and DNA amplification numbers were obtained from cBioPortal. A total of 2,553 upregulated genes were identified. Functional enrichment analysis revealed that these differentially expressed genes (DEGs) were mainly accumulated in metabolism of RNA and the cell cycle. Considering the complexity and heterogeneity of the molecular alterations in HCC, multiple genes for the prognostication of patients with HCC are more reliable than a single gene. Thus, the PPI network and univariate Cox regression analysis were applied to screen candidate genes (small nuclear ribonucleoprotein polypeptide B and B1, nucleoporin 37, Rac GTPase activating protein 1, kinesin family member 20A, minichromosome maintenance 10 replication initiation factor, ubiquitin conjugating enzyme E2 C and hyaluronan mediated motility receptor) that are associated with the overall survival and progression-free survival of patients with HCC. In conclusion, the present study identified a set of genes that are associated with overall survival and progression-free survival of patients with HCC, providing valuable information for the prognosis of HCC.

Prognostic value of small mother against decapentaplegic expression in human gastric cancer.

Gastric cancer is the fifth most common malignancy in the world with alow 5-year survival rate. To date, no study has investigated the prognostic role of the small mother against decapentaplegic (SMAD) in gastric cancer. The association of SMADs with overall survival (OS) of gastric cancer was analyzed on the online Kaplan-Meier (KM) plotter database. Clinical data such as stage, differentiation, gender, treatment, and Her2 mutation status of gastric cancer patients were analyzed. The (E)-SIS3 was used to inhibit SMAD3 expression in gastric cancer cells, and the effects of SMAD3 on gastric cancer cells were analyzed via real-time cellular analysis (RTCA), flow cytometry, colony formation, and immunofluorescence assay. The results showed that the high expression of three members of SMADs (SMAD1, SMAD2, SMAD4) was correlated with afavorable OS of gastric cancer patients. Meanwhile, SMAD3 expression level indicated highly differentiated cancer. We also observed that surgical treatment was associated with high expression level of SMAD1 and SMAD2. Besides, the effect of Her2 on gastric cancer was not noticeable. Moreover, (E)-SIS3 pharmacological assay revealed that inhibition of expression of SMAD3 suppressed the proliferation and migration ability of gastric cancer cells via inducing apoptosis. Collectively, these results demonstrate that the high expression level of three members of SMADs (SMAD1, SMAD2, and SMAD4) is significantly correlated with favorable OS of gastric cancer patients, which is opposite to SMAD3. Thus, SMADs regulate the differentiation of cancer and can be used to guide treatment decisions.

Overexpression of Galectin10 Predicts a Better Prognosis in Human Ovarian Cancer.

To explore the prognosis of Galectins (LGALS) expression on patients with ovarian cancer, the prognosis of LGALS members in ovarian cancer was retrieved and analyzed by using 'Kaplan-Meier plotter' database. The relation of LGALS to overall survival (OS) was evaluated according to histological subtypes, clinical stages and pathological grade. Quantitative real-time polymerase chain reaction and western blot were used to detect the mRNA and protein expression of LGALS in ovarian cancer and normal ovarian cells. Immunohistochemistry was applied to evaluate the different expression of LGALS between cancer and normal tissues. In total patients with ovarian cancer, LGALS4, LGALS8, LGALS10 and LGALS13 mRNA levels were related to a better OS, and LGALS1 to a worse OS. LGALS1 predicted a worse OS in women with serous, stages III+IV or grade II ovarian cancer. LGALS4 predicted a better OS in patients with endometrioid, stages I+II or grade III ovarian cancer. LGALS10 predicted a longer OS in females with serous, all stages, or grade III cancer. LGALS8 overexpression was related to a better OS in all stages. Notably, mRNA and protein expressions of LGALS4, LGALS10 and LGALS13 were decreased in cancer cells than those in normal cells (P<0.05). Additionally, the immunostaining score of LGALS8, LGALS10 and LGALS13 expression were lower but LGALS1 was higher in caner tissues than those in normal tissues (P<0.001). In conclusion, LGALS10 possibly is a valuable biomarker for predicting a favorable prognosis in patients with ovarian cancer, especially with serous, all stages and grade III cancer.

The Expression Patterns and Prognostic Value of the Proteasome Activator Subunit Gene Family in Gastric Cancer Based on Integrated Analysis.

Increasing evidence supports that proteasome activator subunit (PSME) genes play an indispensable role in multiple tumors. The diverse expression patterns, prognostic value, underlying mechanism, and the role in the immunotherapy of PSME genes in gastric cancer (GC) have yet to be fully elucidated. We systematically demonstrated the functions of these genes in GC using various large databases, unbiased in silico approaches, and experimental validation. We found that the median expression levels of all PSME genes were significantly higher in GC tissues than in normal tissues. Our findings showed that up-regulated PSME1 and PSME2 expression significantly correlated with favorable overall survival, post-progression survival, and first progression survival in GC patients. The expression of PSME1 and PSME2 was positively correlated with the infiltration of most immune cells and the activation of anti-cancer immunity cycle steps. Moreover, GC patients with high PSME1 and PSME2 expression have higher immunophenoscore and tumor mutational burden. In addition, a receiver operating characteristic analysis suggested that PSME3 and PSME4 had high diagnostic performance for distinguishing GC patients from healthy individuals. Moreover, our further analysis indicated that PSME genes exert an essential role in GC, and the present study indicated that PSME1 and PSME2 may be potential prognostic markers for enhancing survival and prognostic accuracy in GC patients and may even act as potential biomarkers for GC patients indicating a response to immunotherapy. PSME3 may serve as an oncogene in tumorigenesis and may be a promising therapeutic target for GC. PSME4 had excellent diagnostic performance and could serve as a good diagnostic indicator for GC.

Expression patterns and clinical significances of PBK in lung cancer: an analysis based on Oncomine database.

BACKGROUND: Based on both biological and clinical perspectives, lung cancer is a diverse disease with varied histological subtypes. At present, molecular-targeted drugs have broad application prospects in lung cancer clinical therapy. Here, we explored the expression profile of PDZ-binding kinase (PBK) in lung cancer along with its prognostic potential. METHODS: We employed the Oncomine web resource to explore the differential expression of PBK in LC tissues. Additionally, the prognostic capacity of PBK in lung cancer was explored via the Kaplan-Meier Plotter web resource. RESULTS: Overall, 80 studies documented remarkable differences in the expression of PBK in tumor tissue and healthy control tissue. In all studies, 63 studies showed that PBK was upregulated and 17 studies demonstrated that PBK was downregulated. Of the 80 studies, 63 studies showed an increase in PBK expression in diverse kinds of tumor tissues including the following: bladder cancer, gastric cancer, brain and CNS cancer, cervical cancer, esophageal cancer, head and neck cancer, liver cancer, breast cancer, lung cancer, colorectal cancer, lymphoma, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma and others. In addition, PBK expression was increased in 774 lung cancer tissues (P<0.05). Kaplan-Meier Plotter web resource analysis, revealed that PBK levels were negatively linked to the total survival period of individuals with lung cancer (P<0.05). Subgroup evaluations demonstrated that the prognostic significance of PBK was more obvious in individuals with lung adenocarcinoma. In lung cancer categorized by gender, level I-III differentiation, and stage 1 and stage 3 of clinical staging, the survival advantage of the PBK high-expression group was remarkably lower than that of the low-expression group lung cancer patients (P<0.05). CONCLUSIONS: PBK is an oncogene that is markedly upregulated in lung cancer tissues, and it is correlated with poor prognosis. PBK can be employed as a target in the design of new drugs for lung cancer treatment.

Elevated expression of Tweety homologue 3 predicts poor clinical outcomes in ovarian cancer.

Objective: To define the alteration of tweety homolog (TTYH) expression in patients with ovarian carcinoma (OC) and its correlation to prognosis. Methods: Kaplan-Meier (KM) plotter was used to evaluate the association between TTYHs expression and clinical outcomes of OC patients. The distribution of 20-year overall survival (OS) and progression-free survival (PFS) was estimated using KM survival plots. The mRNA expression of TTYHs in OC and normal ovarian tissues was confirmed by the Oncomine database. Then, using immunohistochemistry assay, the expression of TTYH1 and TTYH3 proteins in serous OC and normal ovarian tissues was detected. In addition, the protein and mRNA levels of TTYH1 and TTYH3 in human OC cell lines ES-2, A2780 and SKOV3 and normal ovarian epithelial cell lines IOSE80 were assessed by western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: TTYH1 possessed meaningful significance in predicting better prognosis in the serous, advanced stage, and well-differentiated OC patients, while TTYH3 expression predicted worse prognosis in serous, late-stage, and poorly differentiated OC patients. High expression of TTYH1 displayed an association with favorable PFS in OC patients with TP53 mutation. However, enhanced TTYH3 was related to an adverse clinical outcome in TP53-mutated OC patients. In addition, TTYH1 was related to a better clinical outcome in OC patients with platinums-based chemotherapy, but only indicated improved overall survival in OC patients who received taxol or platin + taxol chemotherapy. The up-regulated expression of TTYH3 predicted worse survival in OC patients receiving platin, taxol, or platin + taxol chemotherapy regimen. The levels of TTYH3 mRNA and protein were higher in OC cells and tissues when compared to normal ovarian cells and tissues. Conclusions: TTYH3 was a potential predictor for poor clinical outcome in OC patients, particularly in patients with serous, late-stage, poorly differentiated, TP53-mutation or the patients treated with chemotherapy regimens (platin, taxol, or platin + taxol).

The prognostic value of 4.1 mRNA expression in non-small cell lung cancer.

BACKGROUND: The mechanism of 4.1 family in human cancer has not been elucidated. In this study we investigate the value as a prognostic factor of mRNA expression of 4.1 family in non-small cell lung cancer (NSCLC). METHODS: A survival analysis was carried out through the Kaplan-Meier plotter (KM plotter) database. KM's method was used to estimate the prognostic value of 4.1 mRNA expression in NSCLC. RESULTS: Expression of four members are linked to overall survival (OS) in NSCLC patients, among which 4.1G, 4.1B, 4.1R are concerned with first progression (FP), and 4.1G, 4.1R are correlated with post progression survival (PPS) besides. Only 4.1B expression is associated with OS in squamous cell carcinoma, as four members with OS in adenocarcinoma. What's more, 4.1G, 4.1N high mRNA are linked to better FP in adenocarcinoma, and 4.1R overexpression is linked to better PPS. The expression of 4.1G is associated with the prognosis in female, whereas 4.1R in male. Furthermore, 4.1G and 4.1B play as protective roles in non-smoking populations, while 4.1N overexpression is related to poorer PPS. All the four family members are associated with early stage in NSCLC 4.1G, 4.1B and 4.1R are closely related to surgical resection, yet 4.1N has no prognostic significance in patients receiving treatments. However, the results need to be verified in clinical trials further. CONCLUSIONS: Our results offer new opinion about the prognostic value of 4.1 protein family in NSCLC, which may contribute to the development of new therapy for NSCLC.

Mining topoisomerase isoforms in gastric cancer.

DNA topoisomerases essentially remove topological strains generated during DNA replication, transcription, DNA repair, and other cytogenetic processes. However, distinct expression level and prognostic significance of individual topoisomerase isoforms in gastric cancer (GC) remain largely unexplored. In this study, we utilized Oncomine and Kaplan-Meier plotter database to detect the mRNA expression level of individual topoisomerase isoforms as well as assess their prognostic significance in GC patients. With the exception of TOP3B and TOP2B, levels of all topoisomerase isoforms were found to be elevated in GC patients when compared to the normal tissues. Elevated expression of TOP1 and TOP1MT was relevant to longer overall survival (OS) in GC and gastric intestinal type adenocarcinoma (GITA) patients, but not in diffuse gastric adenocarcinoma (DFA) patients. Increased expression of TOP2A and TOP2B was related to better OS in GC, as well as in GITA and DFA patients. In contrast, increased expression TOP3A and TOP3B was associated with shorter OS in GC, as well as in GITA and DFA patients. We also applied the Tumor IMmune Estimation Resource (TIMER) tool to assess the correlations between distinct topoisomerase isoforms and the infiltrating immune cell landscape. Furthermore, we found that down-regulating the expression of TOP3A by shRNA significantly inhibited the proliferation and colony formation in GC cells compared to control shRNA treated cells. Thus our study lays the framework for utilizing topoisomerases in better understanding the complexity and heterogeneity of GC and for developing strategies for novel customized therapy in GC patients.

Comprehensive Evaluation of Endocytosis-Associated Protein SCAMP3 in Hepatocellular Carcinoma.

BACKGROUND: Secretory carrier membrane proteins 3 (SCAMP3) is an endocytosis-associated protein involved in regulating endosomal pathways and the trafficking of vital signaling receptors. This study aimed to comprehensively assess the role of SCAMP3 in hepatocellular carcinoma (HCC) by integrated bioinformatics analysis. METHODS: In this study, bioinformatics databases were used to explore the differential expression status and prognostic value of SCAMP3 gene in HCC, and bioinformatics analyses of survival data and interactors of SCAMP3 were conducted to predict the prognostic value of SCAMP3 in HCC. RESULTS: Using the TCGA data, our data shows that SCAMP3 mRNA expression is most significantly different between liver and hepatocellular carcinoma tissues and higher expression of SCAMP3 has unfavorable prognostic significance in HCC. Tumor grade, stage, and gender also showed a significant relevance with SCAMP3 expression. High SCAMP3 expression of males revealed significantly poorer survival and progression compared with low SCAMP3 expression of males. BioGRID statistics explores 79 unique interactions with SCAMP3 and multiple post translational modifications. Further analysis finds that SOCS2 may negatively correlate with SCAMP3, while GBA, MX1, and DDOST positively correlate with SCAMP3. Moreover, ncRNA analysis shows that SCAMP3 gene expression is positively associated with lncRNA SBF2-AS1 and negatively related with Has-miR-145. The expressions of SBF2-AS1 and Has-miR-145 are also significantly related with survival in HCC. DISCUSSION: SCAMP3 expression can be affected by multiple genes or ncRNAs expression that are associated with survival, thus suggesting that SCAMP3 can be used as a clinical diagnosis and prognostic biomarker in HCC.

Analyses of expressions and prognostic values of Polo-like kinases in non-small cell lung cancer.

BACKGROUND: Despite great advances in its early diagnosis and treatment, lung cancer is still an intractable disease and the second leading cause of cancer-related deaths and morbidity in the world. The family of Polo-like kinases (PLKs) consists of five serine/threonine kinases, which have been reported to participate in various human diseases. However, the expression and prognostic value of each PLK in human lung cancer have not been fully understood. This study analyzed mRNA expression and prognostic value of different PLKs in human non-small cell lung cancer (NSCLC). METHODS: First, mRNA expression of PLKs in patients with NSCLC from the Oncomine and the Gene Expression Profiling Interactive Analysis (GEPIA) database was investigated. Then, a Kaplan-Meier plotter was employed for survival analysis. The sequence alteration for PLKs was analyzed using The Cancer Genome Atlas (TCGA) and the cBioPortal database. Additionally, we analyzed the association among different PLKs using the LinkedOmics database. Finally, the enrichment analysis of PLKs was achieved using the DAVID database. RESULTS: The mRNA expression levels of PLK1 and PLK4 were significantly overexpressed, while mRNA expression level of PLK3 was underexpressed in patients with NSCLC. mRNA expressions of PLK1 and PLK4 were significantly and positively related to the tumor stage of NSCLC. Increased expressions of PLK1, PLK4, and PLK5 and decreased expression of PLK2 were attributed to limited overall survival time in NSCLC. PLK1 was positively correlated with PLK4 via the LinkedOmics database. CONCLUSIONS: PLKs are relevant targets for NSCLC treatment, especially PLK1 and PLK4.

Comprehensive Analysis of the Expression and Prognosis for MCMs in Human Gastric Cancer.

PURPOSES: Minichromosome maintenance (MCM) proteins play an important role in replication and cell cycle progression. Even so, their expression and prognostic roles in cancer remain controversial. METHODS: To address this issue, the study investigated the roles of MCMs in the prognosis of GC by using ONCOMINE, GEPIA2, UALCAN, Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, and DAVID databases. RESULTS: Over expressions of mRNA and cell lines were found in all members of the MCM family, and MCMs were found to be significantly associated with pathological tumor grades in GC patients. Besides, higher mRNA expressions of MCM1/5/7 were found to be significantly associated with shorter overall survival (OS) and progression-free survival (FP) in GC patients, while higher mRNA expression of MCM4/6/9 were connected with favorable OS and FP. Moreover, a high mutation rate of MCMs (68%) was also observed in GC patients. CONCLUSIONS: The results indicated that MCM1/5/7 were potential targets of precision therapy for patients with GC. And MCM4/6/9 were new biomarkers for the prognosis of GC. The results of the study will contribute to supplement the existing knowledge, and help to explore therapeutic targets and enhance the accuracy of prognosis for patients with GC.