Multi-omics approaches identify

Autophagy is a critical cellular homeostatic mechanism, and its dysfunction is linked to invasive breast carcinoma (BRCA). Recently, several omics methods have been applied to explore autophagic regulators in BRCA; however, more reliable and robust approaches for identifying crucial regulators and druggable targets remain to be discovered. Thus, we report here the results of multi-omics approaches to identify potential autophagic regulators in BRCA, including gene expression (EXP), DNA methylation (MET) and copy number alterations (CNAs) from The Cancer Genome Atlas (TCGA). Newly identified candidate genes, such as

Copy number alterations and target genes in chromosome 6 short arm were related to postoperative recurrence of patients with hepatocellular carcinoma / 中华肝胆外科杂志

Objective To investigate the relationship between chromosome 6p copy number alterations (CNAs) and postoperative intrahepatic recurrence of hepatocellular carcinoma (HCC);and to screen for the target genes in CNA(s).Methods Array comparative genomic hybridization (CGH) and expression arrays were used to detect CNAs and differences in gene expression, respectively.The associations between CNAs in 6p and HCC recurrence were analyzed using the log-rank test, the Kaplan-Meier curves and the Cox proportional hazards models on 66 patients who had been follow-up for 2.6 ～ 73.3 months.The differentially expression of genes in the potentially recurrence-related CNAs were further evaluated by the MannWhitney U test on 117 HCCs, which included 109 cases with paired array CGH and expression data.Results 6p CNAs were detected in 46 (69.7％) of the 66 HCCs.Of the 8 CNAs with the most frequent recurrence of over 20％ , a gain at 6p21.1 was independently associated with a 2.3-fold (95％ CI =1.1 ～ 5.1, P ＜ 0.05) increased risk for intrahepatic recurrence and with a more pronounced 3.3-fold (95％ CI =1.4 ～ 8.2, P ＜0.05) risk for early recurrence (≤ 1 year).A panel of 9 genes, including BYSL and RPL7L1 within the documented 6p21.1, were observed to be upregulated in HCCs with 6p21.1 gain when compared with HCCs without (all P ＜ 0.05).A high BYSL expression significantly correlated with a larger tumor size (＞ 6 cm), vascular invasion and advanced tumor stage (all P ＜ 0.05), and high RPL7L1 expression significantly correlated with vascular invasion and advanced tumor stage (all P ＜ 0.05).Conclusion A gain at 6p21.1 was an independently prognostic marker for intrahepatic recurrence of postoperative HCC, particular for early recurrence, and BYSL and RPL7L1 might be the target genes in the recurrence-related 6p21.1 gain.

Association of chromosome 8p copy number alteration with postoperative survival of patients with hepatocellular carcinoma and screening of potential target genes / 中华肝胆外科杂志

Objective To investigate the association of chromosome 8p copy number alteration (CNA) with postoperative survival of patients with hepatocellular carcinoma (HCC),and to screen for possible target genes in the survival-related CNA (s) in 8p.Methods 187 HCC patients were enrolled into the study,which included 66 patients whose follow-up data were available and the follow-up was 2.6 ～ 73.3 months.High-resolution Agilent 244K comparative genomic hybridization (CGH) and Affymetrix U133 Plus2.0 expression arrays were used to screen for CNAs and gene expression differences in 8p.The associations between CNAs in 8p and survival were analyzed using the log-rank test,Kaplan-Meier survival analysis and Cox proportional hazards models.The gene expression levels between the groups were compared by the Mann-Whitney U test.Results Copy number loss on 8p12 (31/66,47％) was significantly associated with reduced survival rate,and HCC patients with 8p12 loss had a 4.1-fold (95％ CI =1.8 ～ 9.4,P ＜ 0.05) increased hazard ratio (HR) for death from HCC,as compared to those without the loss.The mRNA expression levels of the 3 genes in 8p12,including TMEM66,DCTN6,and MAK16,were significantly decreased in HCCs with gene loss than in HCCs without the loss (all P ＜ 0.05),and in non-tumorous liver tissues (all P ＜ 0.05).Conclusion Loss of 8p12 is an independent prognostic marker of unfavorable survival for patients with HCC,and underexpression of genes TMEM66,DCTN6,and MAK16,owing to 8p12 loss,contributed to unfavorable prognosis.

Sex-dependent differences in DNA copy number alterations in hepatocellular carcinoma / 第二军医大学学报

Objective To identify the sex-related DNA copy number alterations (CNA) in hepatocellular carcinoma (HCC). Methods High-resolution array comparative genomic hybridization Carray- CGH) was used to examine 17 female and 46 male HCCs. Two-tailed Fisher's exact test or χ2 test was used to compare the differences in CNA between females and males. Results The overall frequencies and patterns of CNA in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to male on lq21. 3-q22(76. 5% vs 37. 0%, P = 0. 009), llqll(35. 3% vs 0. 0%, P = 0. 000 2) and 19ql3. 31-ql3. 32(23. 5% vs 0. 0%, P = 0. 004), and more loss on 16pll. 2(35. 3% vs 6. 5%, P = 0. 009). Relative to females, male cases had more copy number loss on llqll(63. 0% vs 17. 6%, P = 0. 002). Further analyses showed that llqll gain was correlated with 19ql3. 31-ql3. 32 gain(P = 0. 042) and 16pll. 2 loss(P = 0. 033), while lq21. 3-q22 gain was correlated with 19ql3. 31-ql3. 32 gain(P = 0. 046). Conclusion Our findings suggest that CNA may play an important role in sex-related difference in HCC development.

CGHscape: A Software Framework for the Detection and Visualization of Copy Number Alterations

The robust identification and comprehensive profiling of copy number alterations (CNAs) is highly challenging. The amount of data obtained from high-throughput technologies such as array-based comparative genomic hybridization is often too large and it is required to develop a comprehensive and versatile tool for the detection and visualization of CNAs in a genome-wide scale. With this respective, we introduce a software framework, CGHscape that was originally developed to explore the CNAs for the study of copy number variation (CNV) or tumor biology. As a standalone program, CGHscape can be easily installed and run in Microsoft Windows platform. With a user-friendly interface, CGHscape provides a method for data smoothing to cope with the intrinsic noise of array data and CNA detection based on SW-ARRAY algorithm. The analysis results can be demonstrated as log2 plots for individual chromosomes or genomic distribution of identified CNAs. With extended applicability, CGHscape can be used for the initial screening and visualization of CNAs facilitating the cataloguing and characterizing chromosomal alterations of a cohort of samples.