Clinical and Genetic Characteristics of Early and Advanced Gastric Cancer.

Gastric cancer (GC) persists as the fourth most prevalent cause of global cancer-related mortality, presenting a challenge due to the scarcity of available therapeutic strategies. Precision medicine is crucial not only in the treatment but also in the management of GC. We performed gene panel sequencing with Oncomine focus assay comprising 52 cancer-associated genes and MSI analysis in 100 case-matched gastric cancer cases. A comprehensive analysis of clinical and genetic characteristics was conducted on these genetic results and clinicopathological findings. Upon comparison of clinicopathological characteristics, significant differences between early gastric cancer (EGC) and advanced gastric cancer (AGC) were observed in tumor location (p = 0.003), Lauren classification (p = 0.015), T stage (p = 0.000), and N stage (p = 0.015). The six most frequently mutated genes were PIK3CA (29%, 10/35), ERBB2 (17%, 6/35), KRAS (14%, 5/35), ALK (6%, 2/35), ESR1 (6%, 2/35), and FGFR3 (6%, 2/35). Regarding genetic variation, there was a tendency for the N stage to be higher in GC patients with mutated genes (p = 0.014). The frequency of mutations in GC patients was statistically significantly higher in AGC (n = 24) compared to EGC (n = 11) (odds ratio, 2.792; 95% confidence interval, 1.113 to 7.007; p = 0.026). Six of the ten GC patients carrying mutated genes and exhibiting MSI were classified into intestinal-type and undifferentiated GC, with the location of the tumor being in the lower-third. Among these patients, five harbored mutated PIK3CA, while the remaining patient had a mutation in ALK. Conclusions: AGC patients more frequently exhibited alterations of PIK3CA, KRAS, and ERBB2 as somatic oncogenic drivers, and displayed a higher prevalence of cumulative genetic events, including increased rates of PIK3CA mutations, enhanced detection of immunotherapy biomarkers, and mutations of the ESR1 gene.

Circulating tumour DNA dynamics during alternating chemotherapy and hormonal therapy in metastatic breast cancer: the ALERT study.

PURPOSE: Although changes in circulating tumour DNA (ctDNA) in breast cancer are well described, the kinetics of their fluctuations has not been described over short timescales. We investigated ctDNA dynamics during alternating cycles of chemotherapy and hormonal treatment in pre-treated patients with oestrogen receptor-positive metastatic breast cancer. METHODS: Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression-free survival (PFS), was monitored at 3, 6 and 9 months; secondary endpoints, clinical benefit rate (CBR), safety and tolerability profiles, were also assessed. Importantly, ctDNA fluctuations were monitored using the Oncomine™ Breast cfDNA assay to test whether biomarkers may change rapidly between chemotherapy and aromatase inhibitor (AI) treatment in the setting of advanced breast cancer, potentially reflecting disease dynamics. RESULTS: The median PFS was 202 days (95% CI: 135-undefined) and 235 days (95% CI: 235-undefined) at 6 and 9 months, respectively, with a 50% CBR at both 6 and 9 months. Dynamic changes in ctDNA were observed in short timescales between chemotherapy and AI treatment and support the clinical benefit (CB) seen in individual patients and, critically, appear informative of acquired resistance in real time. CONCLUSION: Changes in ctDNA can occur rapidly and reflect changes in patients' clinical tumour responses (NCT02681523).

Feasibility and Impact of Embedding an Extended DNA and RNA Tissue-Based Sequencing Panel for the Routine Care of Patients with Advanced Melanoma in Spain.

Targeted NGS allows a fast and efficient multi-gene analysis and the detection of key gene aberrations in melanoma. In this study, we aim to describe the genetic alterations in a series of 87 melanoma cases using the oncomine focus assay (OFA), relate these results with the clinicopathological features of the patients, and compare them with our previous study results in which we used a smaller panel, the oncomine solid tumor (OST) DNA kit. Patients diagnosed with advanced melanoma at our center from 2020 to 2022 were included and DNA and RNA were extracted for sequencing. Common mutated genes were BRAF (29%), NRAS (28%), ALK, KIT, and MAP2K1 (5% each). Co-occurring mutations were detected in 29% of the samples, including BRAF with KIT, CTNNB1, EGFR, ALK, HRAS, or MAP2K1. Amplifications and rearrangements were detected in 5% of cases. Only BRAF mutation showed a significant statistical association with sun exposure. For patients with a given genetic profile, the melanoma survival and recurrence-free survival rates were equivalent, but not for stage and LDH values. This expanded knowledge of molecular alterations has helped to more comprehensively characterize our patients and has provided relevant information for deciding the best treatment strategy.

Real-world study of next-generation sequencing diagnostic biomarker testing for patients with lung cancer in Japan.

Our previous real-world studies raised concerns that sequential biomarker testing may lead to increased time to treatment when compared with simultaneous single biomarker testing. The Oncomine Dx target test (ODxTT), a next-generation sequencing-based multiplex biomarker panel test approved in Japan in 2019, is expected to improve time to treatment due to changes in testing methods. This retrospective observational study examined data claims for reimbursement submitted for patients with lung cancer in Japan between June 1, 2019, and March 31, 2020. To evaluate the change in testing prevalence over time and associated improvements in time to treatment, descriptive statistics were used to characterize biomarker testing patterns and rates and evaluate the time to treatment in the time following the approval of ODxTT considering transitions over time during the evaluation period. EGFR and programmed death ligand 1 (PD-L1) were the most tested biomarkers in overall single and simultaneous single testing in the 6177 patients in this study. Individual single biomarker testing gradually decreased over time, except testing for PD-L1, which remained constant. The use of ODxTT gradually increased in this period. Time to treatment decreased from 29 to 22 days with ODxTT, in contrast to single biomarker tests (median 21-23 days overall). These results indicate that biomarker testing frequency changed in Japanese clinical practice during the study and that the use of ODxTT has increased over time, which potentially contributed to the shortening of time to treatment.

A Rapid, Shallow Whole Genome Sequencing Workflow Applicable to Limiting Amounts of Cell-Free DNA.

BACKGROUND: Somatic copy number alterations (sCNAs) acquired during the evolution of breast cancer provide valuable prognostic and therapeutic information. Here we present a workflow for screening sCNAs using picogram amounts of cell-free DNA (cfDNA) and single circulating tumor cells (CTCs). METHODS: We repurposed the Ion ReproSeq PGS™ preimplantation genetic testing kit to perform shallow whole genome sequencing on 178 cfDNA samples (300 pg) and individual CTCs from 10 MBC patients with metastatic breast cancer (MBC) recovered by CellSearch®/DEPArray™. Results were analyzed using a tailored ichorCNA workflow. RESULTS: sCNAs were detected in cfDNA of 41/105 (39%) patients with MBC and 3/23 (13%) primary breast cancers on follow-up (PBC FU), all of whom subsequently relapsed. In 8 of 10 MBCs, individual CTCs had a higher copy number count than matched cfDNA. The median tumor fraction detected by ichorCNA was 0.34 (range 0.17-0.58) for MBC and 0.36 (range 0.31-0.37) for PBC FU. Patients with detectable tumor fraction (≥ 0.1) and TFx and OncomineTM variants had significantly lower overall survival rates (P values P = 0.002 and P < 0.0001 for the log-rank test, respectively). CONCLUSIONS: The ReproSeq PGS assay is rapid, at approximately $120 per sample, providing both a sCNA profile and estimation of the tumor DNA fraction from limiting cfDNA template (300pg) and individual CTCs. The approach could be used to examine the copy number landscape over time to guide treatment decisions, support future trial designs, and be applied to low volume blood spot samples enabling remote monitoring.

Unexpected finding of a rare pathogenic germline BRCA1 variant in an intrahepatic cholangiocarcinoma using the Oncomine Focus DNA assay: clinical and diagnostic implications.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor arising from the epithelial cells of the bile ducts and is the second most common liver cancer after hepatocellular carcinoma. Recently, our Institution launched a Comprehensive Genomic Profiling (CGP) program (named FPG500 program), set up to provide a complete molecular characterization through the TruSight Oncology 500 High Throughput (TSO500HT) solution and samples that do not reach pre-set sample quantity and/or quality thresholds required for TSO500HT, are addressed to Oncomine Focus DNA Assay (OFA) and the Archer's FusionPlex Lung Panel (AFL). METHODS AND RESULTS: Here we report the case of a patient with iCCA enrolled in the FPG500 program and screened by the orthogonal workflow (OFA/AFL). Although BRCA1 is not among the genes declared in the OFA panel, we unexpectedly detected a pathogenic variant in this gene (c.5278-2del, rs878853285). CONCLUSIONS: This case highlights the diagnostic capabilities of CGP, now widely used in both clinical practice and academic setting. The incidental involvement of BRCA1 focuses attention on the role of BRCA genes in biliary tract cancers. Finally, as an orthogonal test confirmed the germline origin of BRCA1 c.5278-2del variant, the germline implications of CGP need to be considered.

European Real-World Assessment of the Clinical Validity of a CE-IVD Panel for Ultra-Fast Next-Generation Sequencing in Solid Tumors.

Molecular profiling of solid tumors facilitates personalized, targeted therapeutic interventions. The ability to perform next-generation sequencing (NGS), especially from small tissue samples, in a short turnaround time (TAT) is essential to providing results that enable rapid clinical decisions. This multicenter study evaluated the performance of a CE in vitro diagnostic (IVD) assay, the Oncomine Dx Express Test, on the Ion Torrent Genexus System for detecting DNA and RNA variants in solid tumors. Eighty-two archived formalin-fixed paraffin embedded (FFPE) tissue samples from lung, colorectal, central nervous system, melanoma, breast, gastric, thyroid, and soft tissue cancers were used to assess the presence of single nucleotide variants (SNVs), insertions and deletions (indels), copy number variations (CNVs), gene fusions, and splice variants. These clinical samples were previously characterized at the various academic centers using orthogonal methods. The Oncomine Dx Express Test showed high performance with 100% concordance with previous characterization for SNVs, indels, CNVs, gene fusions, and splice variants. SNVs and indels with allele frequencies as low as 5% were correctly identified. The test detected all the expected ALK, RET, NTRK1, and ROS1 fusion isoforms and MET exon 14-skipping splice variants. The average TAT from extracted nucleic acids to the final variant report was 18.3 h. The Oncomine Dx Express Test in combination with the Ion Torrent Genexus System is a CE-IVD-compliant, performant, and multicenter reproducible method for NGS detection of actionable biomarkers from a range of tumor samples, providing results in a short TAT that could support timely decision- making for targeted therapeutic interventions.

Real-world data on NGS using the Oncomine DxTT for detecting genetic alterations in non-small-cell lung cancer: WJOG13019L.

Considering the increasing number of identified driver oncogene alterations, additional genetic tests are required to determine the treatment for advanced non-small-cell lung cancer (NSCLC). Next-generation sequencing can detect multiple driver oncogenes simultaneously, enabling the analysis of limited amounts of biopsied tissue samples. In this retrospective, multicenter study (UMIN ID000039523), we evaluated real-world clinical data using the Oncomine Dx Target Test Multi-CDx System (Oncomine DxTT) as a companion diagnostic system. Patients with NSCLC who were tested for a panel of 46 genes using the Oncomine DxTT between June 2019 and January 2020 were eligible for enrollment. Patients from 19 institutions affiliated to the West Japan Oncology Group were recruited. The primary endpoint of the study was the success rate of genetic alteration testing in four driver genes (EGFR, ALK, ROS1, and BRAF) using the Oncomine DxTT. In total, 533 patients were enrolled in the study. The success rate of genetic alteration testing for all four genes was 80.1% (95% CI 76.5%-83.4%). Surgical resection was associated with the highest success rate (88.0%), which was significantly higher than that for bronchoscopic biopsy (76.8%, P = .005). Multivariate analysis revealed a significant difference for surgical resection alone (P = .006, 95% CI 1.36-6.18, odds ratio 2.90). Although the success rate of genetic alteration testing immediately after Oncomine DxTT induction was not sufficient in this study, optimizing specimen quantity and quality may improve the use of driver gene testing in clinical settings.

Bioinformatics Analysis and Experimental Study of Exonuclease 1 Gene in Lung Adenocarcinoma.

The objective of this study is to examine the role of Human Exonuclease 1(EXO1) gene in the diagnosis and prognosis of lung adenocarcinoma (LUAD), and predict the signal pathways EXO1 involved in. The clinical parameters and EXO1 expression datasets of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), Oncomine and Gene Expression Omnibus (GEO) database. Wilcoxon rank-sum test was performed to determine whether EXO1 expression was upregulated in LUAD. The correlation between EXO1 expression and clinicopathological parameters was analyzed by Chi-square test, and Kaplan-Meier survival analysis and COX regression models were adopted to analyze and verify the correlation of EXO1 expression with OS of LUAD patients for the exploration of prognostic value of EXO1 in LUAD patients. The signaling pathway related to EXO1 was predicted by gene set enrichment analysis (GSEA). In addition, sera from LUAD patients and healthy subjects were collected, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was conducted to detect EXO1 expression. EXO1 expression was upregulated in LUAD patients with respect to normal individuals. EXO1 expression was negatively correlated with the prognosis and thus could independently predict the prognosis of LUAD patients. EXO1 gene was involved in 128 signal pathways, of which 9 pathways may be closely related. EXO1 was highly expressed in the blood of LUAD patients. High EXO1 expression can serve as an independent risk factor for poor prognosis, and the expression of serum EXO1 has certain diagnostic value for LUAD.

Bioinformatics screening of biomarkers related to liver cancer.

BACKGROUND: Liver cancer is a common malignant tumor in China, with high mortality. Its occurrence and development were thoroughly studied by high-throughput expression microarray, which produced abundant data on gene expression, mRNA quantification and the clinical data of liver cancer. However, the hub genes, which can be served as biomarkers for diagnosis and treatment of early liver cancer, are not well screened. RESULTS: Here we present a new method for getting 6 key genes, aiming to diagnose and treat the early liver cancer. We firstly analyzed the different expression microarrays based on TCGA database, and a total of 1564 differentially expressed genes were obtained, of which 1400 were up-regulated and 164 were down-regulated. Furthermore, these differentially expressed genes were studied by using GO and KEGG enrichment analysis, a PPI network was constructed based on the STRING database, and 15 hub genes were obtained. Finally, 15 hub genes were verified by applying the survival analysis method on Oncomine database, and 6 key genes were ultimately identified, including PLK1, CDC20, CCNB2, BUB1, MAD2L1 and CCNA2. The robustness analysis of four independent data sets verifies the accuracy of the key gene's classification of the data set. CONCLUSIONS: Although there are complicated differences between cancer and normal cells in gene functions, cancer cells could be differentiated in case that a group of special genes expresses abnormally. Here we presented a new method to identify the 6 key genes for diagnosis and treatment of early liver cancer, and these key genes can help us understand the pathogenesis of liver cancer more deeply.

NAT1 is a critical prognostic biomarker and inhibits proliferation of colorectal cancer through modulation of PI3K/Akt/mTOR.

The aim of this study was to analyze the correlations between NAT1 and clinicopathological features of and prognosis in colorectal cancer (CRC). RNA sequencing data and clinical information were retrieved from The Cancer Genome Atlas database. Wilcoxon test, logistic regression and Kaplan-Meier method were used to estimate the association between NAT1 and prognosis in CRC. In vitro experiments were conducted to confirm the role of NAT1. NAT1 is significantly less expressed in CRC and independently associated with poor prognosis in CRC patients. The authors further confirmed that expression of NAT1 was significantly lower in SW116 colon cancer cells than in NCM460 cells. Overexpressed NAT1 obviously inhibited the growth of CRC cells by downregulating phosphorylation of the PI3K/Akt/mTOR signaling pathway. NAT1 may be a potential therapeutic target for CRC.

Lay abstract Colorectal cancer (CRC) is a common malignancy worldwide. Because of the limited understanding of the pathogenesis and prognostic factors associated with CRC, the treatment effect in CRC remains poor. In the present study, the authors demonstrate that NAT1 is significantly less expressed in CRC and independently associated with poor prognosis in CRC patients. NAT1 may exert antitumor activity by inhibiting phosphorylation of the PI3K/Akt/mTOR signaling pathway. These results suggest that NAT1 may be a prognostic factor in and therapeutic target for CRC.

Feasibility of next-generation sequencing (Oncomine™ DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients.

BACKGROUND: The Oncomine™ Dx Target Test based on next-generation sequencing has been approved for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. METHODS: We assessed the tissue sample factors that affect the success rate of Oncomine™ Dx Target Test companion diagnostics and the feasibility of using biopsy specimens for Oncomine™ Dx Target Test companion diagnostics in advanced non-small-cell lung cancer patients. RESULTS: Ninety-nine biopsy samples were subjected to genetic testing using the Oncomine™ Dx Target Test companion diagnostics to detect v-raf murine sarcoma viral oncogene homologue B1 mutations (Cohort 1), and 136 biopsy samples were examined using Oncomine™ Dx Target Test companion diagnostics for the detection of multiple oncogenic mutations (Cohort 2) between July 2018 and April 2020. We retrospectively collected clinical and pathological data, including tissue size and tumour cell content. The success rate was 77% (76/99) in Cohort 1 and 93% (127/136) in Cohort 2. In Cohort 1, the success rate was significantly associated with the tumour cell content: the success rate was 63% for samples with a tumour cell content of <20%, whereas it was 83% for samples with a tumour cell content of 20% or higher (P = 0.0446). The tissue size also affected the success rate: a success rate of 57% was obtained for tissue sizes <4 mm2, whereas a success rate of 95% was obtained for tissue sizes of 4 mm2 or larger (P < 0.0001). In Cohort 2, the success rate was 100% when tumour specimens with a tissue size of 4 mm2 or larger were used. CONCLUSIONS: Tissue size and tumour cell content were significantly associated with the success rate of Oncomine™ Dx Target Test companion diagnostics.

Jab1/Cops5: a promising target for cancer diagnosis and therapy.

C-Jun activation domain-binding protein1 (Jab1), the fifth component of the constitutive photomorphogenic-9 signalosome (COPS5/Csn5) complex, functions in several cellular processes to affect different signaling pathways. Dysregulation of Jab1/Csn5 both restrains tumor suppressors and activates oncogenes to contribute oncogenesis. Jab1 overexpressed in various tumors and played an essential part in cancer initiation, progression and prognosis, which has spurred strong research interest in developing inhibitors for cancer therapy. Here, we summarize the multiple signaling pathways and functions of Jab1/Csn5 in tumorigenesis. By querying the Oncomine database, a cancer microarray database and web-based data-mining platform aimed at facilitating discovery from genome-wide expression analyses, we investigated statistically the differential expression of Jab1/Csn5 between different cancer samples and the corresponding normal tissue samples, cancer samples with different histological types, different cancer types, and different clinical outcomes. These statistical data confirmed the significant role of Jab1/Csn5 in carcinogenesis, indicating Jab1/Csn5 as a biomarker and a therapeutic target in different cancers.

Overexpression of DSCR1 prevents proliferation and predicts favorable prognosis in colorectal cancer patients.

OBJECTIVES: Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. However, little is known about the role of DSCR1 in CRC progression. The present study aimed to elucidate the clinicopathological significance, prognostic, and function roles of DSCR1 in CRC. METHODS: Firstly, we analyzed DSCR1 expression in 58 paired CRC samples and Oncomine database. Then, we analyzed DSCR1 expression in two independent CRC cohorts (test cohort: n = 70; validation cohort: n = 58) and tested its overall survival (OS) by Kaplan-Meier survival analyses. Finally, we overexpressed DSCR1 in two CRC cell lines DLD1 and LoVo and analyzed its effect on cell cycle and senescence. RESULTS: DSCR1 expression was significantly decreased in CRC samples and associated with clinicopathologic features of CRC patients, such as tumor size, lymph node metastasis, and TNM stage. CRC patients with low expression of DSCR1 had shorter overall survival (OS). Kaplan-Meier survival analyses showed that the expression of DSCR1 was significant factor for OS in both cohorts. Multiple Cox regression analysis showed that DSCR1 expression was an independent prognostic marker for OS in test cohort. Overexpression of DSCR1 isoform 4 (DSCR1-4) increased p21, p16, p-NFAT1, and p-NFAT2, while decreased CDK2, CDK4, and Cyclin D1 in CRC cells. In addition, overexpression of DSCR1-4 prevented proliferation and colony formation, and induced senescence in vitro. Moreover, overexpression of DSCR1-4 inhibited tumor growth and tumor angiogenesis in vivo. CONCLUSIONS: Our study found high expression of DSCR1 contributes to favorable prognosis of CRC patients and prevents cell cycle and proliferation of CRC cells, indicating a critical tumor suppressive role in CRC progression.

In silico analysis of differentially expressed genesets in metastatic breast cancer identifies potential prognostic biomarkers.

BACKGROUND: Identification of specific biological functions, pathways, and appropriate prognostic biomarkers is essential to accurately predict the clinical outcomes of and apply efficient treatment for breast cancer patients. METHODS: To search for metastatic breast cancer-specific biological functions, pathways, and novel biomarkers in breast cancer, gene expression datasets of metastatic breast cancer were obtained from Oncomine, an online data mining platform. Over- and under-expressed genesets were collected and the differentially expressed genes were screened from four datasets with large sample sizes (N > 200). They were analyzed for gene ontology (GO), KEGG pathway, protein-protein interaction, and hub gene analyses using online bioinformatic tools (Enrichr, STRING, and Cytoscape) to find enriched functions and pathways in metastatic breast cancer. To identify novel prognostic biomarkers in breast cancer, differentially expressed genes were screened from the entire twelve datasets with any sample sizes and tested for expression correlation and survival analyses using online tools such as KM plotter and bc-GenExMiner. RESULTS: Compared to non-metastatic breast cancer, 193 and 144 genes were differentially over- and under-expressed in metastatic breast cancer, respectively, and they were significantly enriched in regulating cell death, epidermal growth factor receptor signaling, and membrane and cytoskeletal structures according to the GO analyses. In addition, genes involved in progesterone- and estrogen-related signalings were enriched according to KEGG pathway analyses. Hub genes were identified via protein-protein interaction network analysis. Moreover, four differentially over-expressed (CCNA2, CENPN, DEPDC1, and TTK) and three differentially under-expressed genes (ABAT, LRIG1, and PGR) were further identified as novel biomarker candidate genes from the entire twelve datasets. Over- and under-expressed biomarker candidate genes were positively and negatively correlated with the aggressive and metastatic nature of breast cancer and were associated with poor and good prognosis of breast cancer patients, respectively. CONCLUSIONS: Transcriptome datasets of metastatic breast cancer obtained from Oncomine allow the identification of metastatic breast cancer-specific biological functions, pathways, and novel biomarkers to predict clinical outcomes of breast cancer patients. Further functional studies are needed to warrant validation of their roles as functional tumor-promoting or tumor-suppressing genes.

Expression, immune infiltration and clinical significance of SPAG5 in hepatocellular carcinoma: A gene expression-based study.

BACKGROUND: Overexpression of sperm-associated antigen 5 (SPAG5) is a marker of poor prognosis in numerous tumors and is recognized as an index of tumor proliferation; however, its expression in liver cancer remains unclear. METHODS: The Oncomine (https://www.oncomine.org) and Timer (https://cistrome.shinyapps.io/timer) databases were used to analyze the expression of SPAG5 in liver hepatocellular carcinoma (HCC) and normal liver tissues. The relationship between the expression of SPAG5 and immune infiltration of HCC was investigated using the Timer and GEPIA (http://gepia.cancer-pku.cn) databases, and the mechanism was analyzed using Gene Set Enrichment Analysis. A Kaplan-Meier Plotter (http://kmplot.com/analysis) was used to evaluate the effect of SPAG5 on the prognosis of patients with HCC. RESULTS: The results revealed that the SPAG5 expression level was positively correlated with the infiltration levels of CD8+ T cells, macrophages, neutrophils, and especially B cells and dendritic cells. In addition, SPAG5 expression was significantly associated with T cell exhaustion. The overall survival time, progression-free survival time, recurrence-free survival time and disease-specific survival time were significantly reduced for HCC patients with high SPAG5 expression (p < 0.01) and high expression of SPAG5 was significantly associated with a poor overall survival time and progression-free survival time of grade and stage II-III HCC (p < 0.05) but not with stage I HCC (p > 0.05). Additionally, the expression of SPAG5 is related to the p53 and cell cycle signal pathways. CONCLUSIONS: In conclusion, SPAG5 is not only a marker of immune infiltration and poor prognosis, but also a potential therapeutic target for liver cancer.

Systematic analysis of multigene predictors in gastric cancer exploiting gene expression signature.

Gastric cancer (GC) is the second most common cause of cancer death worldwide but could be more curable if diagnosed at an earlier stage. At present, the capability to predict the efficaciousness of molecular diagnosis for GC for each patient remains elusive. The purpose of this study was to identify tumor biomarkers through systems analysis of multigene predictors exploiting the available data resource. In this study, we investigated the top 10% overexpressed genes in GC from five data sets of the Oncomine platform, with 265 GC samples versus 174 normal gastric mucosa samples. Sixteen candidate genes were identified as predictors of GC, of which 14 genes were verified through the comparison of expression levels in specimens from normal (chronic gastritis, 21 samples) and GC groups (38 samples). In addition, unique molecular portraits of diffuse adenocarcinoma (DA), intestinal adenocarcinoma (IA), and mixed adenocarcinoma (MA) were studied through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, where DA showed higher extracellular matrix alteration while IA and MA showed higher cell-cycle alteration than other types. We also found that the elevated expressions of genes during GC progression were independent of gene mutations, and high core-binding factor subunit ß expression is correlated with a high overall survival rate in GC patients. Our research may provide an efficient clinical diagnosis of GC at an early stage with high accuracy and thus help improve the overall survival rate through early therapeutic interventions.

Low expression of NCOA5 predicts poor prognosis in human cervical cancer and promotes proliferation, migration, and invasion of cervical cancer cell lines by regulating notch3 signaling pathway.

Nuclear receptor coactivator 5 (NCOA5) specifically enhances estrogen receptor α-modulated transcriptional activity. As a novel tumor suppressor, depletion of NCOA5 is associated with the development of a variety of tumors, but its function in cervical cancer is currently unclear. In this study, we addressed how expression of NCOA5 changed in the development of human cervical cancer and its association with clinicopathological features, prognosis, and biology characteristics of cervical cancer. Analysis of the microarrays in the Oncomine database indicated that NCOA5 expression was lower in human cervical squamous cell carcinoma tissues than that in normal cervical tissues. That was corroborated by our experiments using fresh tissues: the expression levels of NCOA5 messenger RNA and protein were both significantly decreased in cervical cancer tissues compared with paired adjacent nontumor tissues (P < 0.01). Low expression of NCOA5 is associated with the International Federation of Gynecology and Obstetrics stage ( P = 0.043) and histological grade ( P = 0.018) of human cervical cancer. In addition, patients possessing low NCOA5 expression had poorer prognosis. Univariate and multivariate Cox regression analyses indicated that low NCOA5 expression may be an independent prognostic factor for poorer overall survival in cervical cancer. Further, downregulation of NCOA5 expression results in a significant increase in proliferation, migration, and invasion of HeLa cells. Data of xenograft tumor on BALB/c nude mice manifested that HeLa cells with low NCOA5 expression tend to form larger tumors than negative control ones. In contrast, overexpression of NCOA5 expression leads to the opposite results. Finally, we found that NCOA5 might affect the biological function of human cervical cancer cells by mediating the notch3 signaling pathway. These findings suggest that NCOA5 acts as a tumor suppressor to inhibit tumorigenicity, migration, and invasion, and thus represents a potential novel prognostic marker for overall survival in cervical cancer.

TIGD1, a gene of unknown function, involves cell-cycle progression and correlates with poor prognosis in human cancer.

BACKGROUND: Trigger transposable element-derived 1 (TIGD1), a human species-specific gene, was identified as a cell cycle-related differentially expressed gene during the formation of liver cancer. As far as we know, there are no reports about the function of TIGD1. This study aimed to explore the expression of TIGD1 in human cancers and establish whether elevated TIGD1 can be used as a prognostic cancer biomarker and its potential role in cancer. METHODS: Molecular profiling of TIGD1 in human cancers was assessed using a series of databases, including Oncomine, COSMIC, Kaplan-Meier, UCSC, and cBioPortal. RESULTS: We found that TIGD1 overexpressed in colorectal, gastric, liver, lung, and pancreatic cancers than their normal tissues and its expression might be negatively related with the prognosis. The TIGD1 coexpression genes were obtained from cBioPortal and analyzed using ClueGO plugin in Cytoscape to predict the function of TIGD1. CONCLUSIONS: In summary, the elevated TIGD1 expression is coupled with a malignant survival rate in several cancers. It may play its role by regulating cell-cycle progression. These findings provide fresh insight into our understanding of TEs in cancers. As a previously unreported gene, future research is required to validate our findings and illuminate the molecular mechanisms. In conclusion, we systemically analyze the expression, prognostic value, and likely role of TIGD1, the unknown function gene, in cancer. Our finding provides evidence that TIGD1 involve in the cell cycle. These findings provide fresh insight into our understanding of TEs in cancers. Next, the detailed mechanism of TIGD1 needs to be studied in the future.