A new multivariate test formulation: theory, implementation, and applications to genome-scale sequencing and expression

Xu, Lei

doi:10.1186/s40535-015-0016-4

Cited by 13 publications

(16 citation statements)

References 35 publications

(11 reference statements)

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“…Moreover, though it is known that the 5-year OS is a gold standard as an endpoint in clinical trials (19), 3-year PFS, as a potential surrogate of 5-year OS, has also received much attention recently (20). Hence we adopted the IHT (21) that incorporates both 5-year OS and 3-year PFS to evaluate each gene based on both P-value and classification accuracy. We used the FDA-based PT-test to select candidate mRNAs into a twin-set with one comprising of top-50 mRNAs with smallest Student’s P-values and the other comprising of top-50 mRNAs with highest classification accuracies.…”

Section: Methodsmentioning

confidence: 99%

Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

Huang

Hou

et al. 2019

Chinese Journal of Cancer Research

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ObjectiveTumor heterogeneity renders identification of suitable biomarkers of gastric cancer (GC) challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.MethodsWe first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase (GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state (E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition (EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets. ResultsWe found that higher expression of GPI in GC correlated with prolonged survival of patients. Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage II/III. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells. ConclusionsOur findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis, allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.

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Section: Methodsmentioning

confidence: 99%

Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

Huang

Hou

et al. 2019

Chinese Journal of Cancer Research

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“…The above tests reject the H0 as long as at least one of dimensions is rejected, and they ignore the roles of dimensions and their combination just as described in the Fig 3(a) of [5]. The S-space BBT is one of the directional test and is described in the Fig 6(a) of [5]. The way to achieving the combination is also given in Eq.…”

Section: Statistic-space Boundary Based Testmentioning

confidence: 99%

“…The Fisher's method combined the Pvalue of each hypothesis into the Chi-square statistic in linear form, but much information is lost. And the third road is that we perform the multivariate test in the high dimensional space directly, so that it can break through the two limitations that the existing methods suffered from [5]. First, these existing methods regardless of the relationship between the dimensions; Second, the direction for each component is not taken into consideration.…”

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confidence: 99%

A Comparative Study of Joint-SNVs Analysis Methods and Detection of Susceptibility Genes for Gastric Cancer in Korean Population

2017

Lecture Notes in Computer Science

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Abstract. Many joint-SNVs (single-nucleotide variants) analysis methods were proposed to tackle the 'missing heritability' problem, which emphasizes that the joint genetic variants can explain more heritability of traits and diseases. However, there is still lack of a systematic comparison and investigation on the relative strengths and weaknesses of these methods. In this paper, we evaluated their performance on extensive simulated data generated by varying sample size, linkage disequilibrium (LD), odds ratios (OR), and minor allele frequency (MAF), which aims to cover almost all scenarios encountered in practical applications. Results indicated that a method called Statistics-space Boundary Based Test (S-space BBT) showed stronger detection power than other methods. Results on a real dataset of gastric cancer for Korean population also validate the effectiveness of the S-space BBT method.

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“…Previously, we conducted a gene expression profiling on 198 GC and paired adjacent nontumor tissues from Chinese patients by lncRNA array with 40,914 transcripts. Then, a recently proposed analytical method namely FDA-based PT-test was performed according to the Table 3 & 4 from the previous work by Xu27, which was designed to screen prognostic marker of lncRNAs based on gene expression profiling data of tumor and paired nontumor tissues. As a result, a set of lncRNAs, including a novel lncRNA p4516 (ID: ENST00000563647.1, refer to Ensembl genome browser 94), closely associating with prognosis were revealed (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

<p>The novel lncRNA p4516 acts as a prognostic biomarker promoting gastric cancer cell proliferation and metastasis</p>

Nie

Han

Huang

et al. 2019

CMAR

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Purpose: Emerging evidence has shown that long noncoding RNAs (lncRNAs) participate in oncogenesis and tumor progression. We previously found a novel lncRNA p4516 which was closely associated with prognosis by preliminary study of lncRNA expression profile from paired tumors and nontumor tissues in 198 gastric cancer (GC) patients. However, the exact biological functions and the underlying molecular mechanisms of p4516 in gastric tumorigenesis still remain unclear. Materials and methods: The RNA fluorescence in situ hybridization (RNA-FISH) analysis, cytoplasmic and nuclear RNA isolation and qRT-PCR were applied to determine the subcellular localization of p4516. Expression levels of p4516 were assessed using qRT-PCR in both GC cell lines and in 142 primary GC tissues. Correlations between p4516 expression and GC patients’ clinicopathological parameters were analyzed. Gain- and loss-of-function experiments were employed to investigate the role of p4516 in proliferation, migration and invasion both in vitro and in vivo. In addition, Western blotting and immunohistochemical staining were used to examine the protein expression levels. Results: LncRNA p4516 was mainly localized in the nucleus of GC cells and p4516 tended to have higher expression levels in GC cells compared to the normal gastric mucosa-derived cells GES-1. Furthermore, higher expression levels of p4516 correlated with worse clinical outcomes in GC patients and acted as an independent prognostic biomarker. Functional analysis revealed that p4516 participated in the regulation of GC cell proliferation, invasion and migration both in vivo and in vitro. Moreover, p4516 was involved in epithelial–mesenchymal transition (EMT) in GC cells. Conclusion: Our study demonstrated the oncogenic role of novel lncRNA p4516 in the gastric carcinogenesis for the first time. High expression of p4516 may act as prognostic marker in patient with gastric cancer.

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A new multivariate test formulation: theory, implementation, and applications to genome-scale sequencing and expression

Cited by 13 publications

References 35 publications

Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

A Comparative Study of Joint-SNVs Analysis Methods and Detection of Susceptibility Genes for Gastric Cancer in Korean Population

<p>The novel lncRNA p4516 acts as a prognostic biomarker promoting gastric cancer cell proliferation and metastasis</p>

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