Clinical significance of LIN28A gene polymorphisms and expression in pan-cancer: a meta-analysis and bioinformatic analysis.

Several studies have reported the relationship between LIN28A gene polymorphisms (rs3811463 T > C and rs34787247 G > A) and cancer susceptibility, but the results are inconsistent and need further clarification. The current study aimed to evaluate their relationship and also to explore the relationship between LIN28A gene expression and immune infiltration, tumor stage, survival prognosis, and drug sensitivity in pan-cancer. The meta-analysis and data mining were completed by STATA software and the GSCA platform, respectively. The meta-analysis showed that the rs3811463 polymorphism was not associated with cancer susceptibility, while the rs34787247 polymorphism was associated with cancer susceptibility in the Chinese population [AA vs. GG: Odd Ratio (OR)=1.98, 95% Confidence Interval (CI)=1.35-2.89, PZ<0.001; GA vs. GG: OR = 1.17, 95%CI= 1.01-1.36, PZ=0.04; (AA + GA) vs. GG: OR = 1.24, 95%CI = 1.07-1.43, PZ=0.004; AA vs. (GA + GG): OR = 1.90, 95%CI = 1.30- 2.78, PZ=0.001; A vs. G: OR = 1.27, 95%CI = 1.12-1.44, PZ<0.001]. LIN28A gene expression was associated not only with immune infiltration, pathological stage, and survival prognosis of certain cancers, but also with sensitivity to multiple anticancer drugs, such as cisplatin, pazopanib, olaparib, and selumetinib. In conclusion, the current study suggested that the rs34787247 G > A polymorphism might be used as a cancer risk marker in the Chinese population, and LIN28A might serve as a prognostic marker and therapeutic target for certain cancers.

Causal association between urine albumin-to-creatinine ratio and risk of colorectal cancer: A two-sample Mendelian randomization study.

Previous observational studies have investigated the association between urinary albumin excretion and the risk of colorectal cancer (CRC), but the results have been inconsistent. This study aimed to explore the causal association between urine albumin-to-creatinine ratio (ACR) and CRC risk through a two-sample Mendelian randomization (MR) analysis. The genome-wide association study (GWAS) data of ACR (n = 382,500) and CRC (CRC: 6,509 cases and 287,137 controls) were obtained from the IEU OpenGWAS project website and the FinnGen database, respectively. The TwoSampleMR and MR-PRESSO R packages were used to search for and analyze genetic variations that served as instrumental variables for ACR. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the inverse-variance weighted method, MR-Egger, and weighted median. Genetically predicted ACR was not associated with CRC risk (all P > 0.05). Further analysis based on the site of onset (colon or rectum) also did not show a significant association (all P > 0.05). MR-PRESSO, MR-Egger regression and leave-one-out sensitivity analysis all indicated that the current results were robust and reliable. These findings suggest that ACR does not affect CRC risk and may not be used as a marker of CRC risk in clinical practice. However, relevant studies especially in ethnically diverse populations are still needed to confirm the current findings.

Bioinformatics and meta-analysis of the clinical significance of RECK expression and its genetic polymorphisms in cancer.

RECK plays an important role in the development of cancer. The current study focuses on exploring the clinical significance of RECK expression in cancer by mining public data and also evaluating the relationship between genetic polymorphisms of the RECK gene and cancer risk through meta-analysis. The results showed that RECK expression was not only associated with survival prognosis and immune infiltration in many types of cancers, but also with multiple drug sensitivity in pan-cancer. In addition, the RECK rs10814325 polymorphism was also associated with cancer risk under the homozygote comparison model (CC vs. TT: OR = 1.64, 95%CI = 1.03-2.61, p = 0.04) and the recessive genetic model [CC vs. (CT + TT): OR = 1.55, 95%CI = 1.27-1.89, p < 0.01]. In conclusion, these findings suggest that RECK expression levels may serve as a valuable indicator for assessing cancer prognosis in some cancers as well as drug sensitivity in pan-cancer, and its rs10814325 polymorphism may be used to assess cancer risk.

Clinical significance of BTLA gene expression and rs1982809 polymorphism in pan-cancer.

The association between the B and T lymphocyte attenuator (BTLA) gene rs1982809 polymorphism and cancer susceptibility has been reported, but these findings are inconsistent. In addition to clarifying the relationship between the rs1982809 polymorphism and cancer susceptibility, the current study also explored the clinical significance of BTLA gene expression. The GSCA tool and Stata software were used to explore the association between BTLA gene expression and tumor stage, immune infiltration, survival prognosis, and drug sensitivity for pan-cancer, and the association of BTLA gene rs1982809 polymorphism with cancer susceptibility, respectively. BTLA gene expression was associated not only with the pathologic stages of thyroid carcinoma, skin cutaneous melanoma, and kidney renal clear cell carcinoma, but also with immune infiltration in 33 types of cancers. In addition, BTLA gene expression was linked to survival prognosis in 8 types of cancers and the sensitivity of 255 drugs such as 5-Fluorouracil, docetaxel, and methotrexate. A meta-analysis of 7 relevant studies with 4002 cancer patients and 5278 healthy controls showed that the BTLA gene rs1982809 polymorphism was unrelated to cancer susceptibility under all genetic models. However, a country-based stratification analysis suggested that the rs1982809 polymorphism could reduce cancer susceptibility in Polish and Tunisian populations. In conclusion, BTLA is expected to serve as a prognostic marker and therapeutic target for certain cancers, and the rs1982809 polymorphism is expected to serve as a cancer susceptibility marker in Polish and Tunisian populations.

Associations between KCNQ1OT1 genetic variation rs10766212 and susceptibility to colorectal cancer and clinical stage in a Chinese Han population.

KCNQ1OT1 has been linked to the development and progression of colorectal cancer (CRC). As a result, functional polymorphisms in the KCNQ1OT1 gene may have a role in CRC formation and progression. The goal of this study was to see if the rs10766212 polymorphism on the KCNQ1OT1 gene was linked to CRC susceptibility and clinical stage in a Chinese Han population. The case-control research comprised a total of 576 CRC patients and 606 healthy controls. The genotype of the rs10766212 polymorphic locus was determined using the Sanger sequencing technique. We found that the KCNQ1OT1 rs10766212 polymorphism was not related to CRC susceptibility; however, it was connected with the clinical stage of CRC. Patients with CRC who had the rs10766212 T allele had a lower risk of stage III/IV tumors than those who had the rs10766212 C allele. Furthermore, CRC tissues with the rs10766212 CC genotype showed a significant negative connection between KCNQ1OT1 and hsa-miR-622 expression. The luciferase assay showed that the rs10766212 C allele might contribute to the adsorption of KCNQ1OT1 on hsa-miR-622. In conclusion, the rs10766212 polymorphism altering hsa-miR-622 binding is linked to the clinical stage of CRC and may serve as a biomarker for predicting CRC progression in the Chinese Han population. However, better-designed studies are still needed to confirm the current findings.

Association of RTN4 indel polymorphisms with the risk of tumorigenesis in the Chinese Han population.

Although studies have reported the association of two insertion/deletion (indel) polymorphisms in the 3'-untranslated region (UTR) of the RTN4 gene with the risk of tumorigenesis, the findings are inconsistent and require further explanation. Comprehensive literature searches were undertaken in Pubmed, Embase, Web of Science, China National Knowledge Infrastructure, and WangFang database. The risk of tumorigenesis was determined using odds ratios (ORs) and 95% confidence intervals (CIs) based on STATA 12.0 software. A total of four case-control studies with 1214 patients and 1850 controls focused on the RTN4 gene TATC/- polymorphism and five case-control studies with 1625 patients and 2321 controls on the RTN4 gene CAA/- polymorphism. Pooled analysis showed that the TATC/- polymorphism was not associated with the risk of tumorigenesis under all genetic models and the CAA/- polymorphism was significantly associated with the risk of tumorigenesis under the homozygote genetic model (Del/Del vs. Ins/Ins: OR=1.32, 95%CI=1.04-1.68, P=0.02). In conclusion, the current findings suggested that the CAA/- polymorphism in the 3'-UTR of the RTN4 gene was significantly associated with the risk of tumorigenesis in the Chinese population and may serve as a valuable marker for predicting tumor risk.

TP73-AS1 rs3737589 Polymorphism is Associated With the Clinical Stage of Colorectal Cancer.

Objective: TP73-AS1 can promote the occurrence and development of a variety of tumors, including colorectal cancer (CRC). The current study aimed to investigate the association between a potentially functional genetic polymorphism (rs3737589 T > C) on the TP73-AS1 gene and the susceptibility and clinical stage of CRC in a Chinese Han population. Methods: The polymorphic genotyping was performed by the SNaPshot method. The real-time quantitative PCR method and the luciferase assay were used separately to explore genotype-tissue expression and the function of the genetic polymorphism. Results: A total of 576 CRC patients and 896 healthy controls were included in the current study. The rs3737589 polymorphism was not associated with CRC susceptibility but was associated with the CRC stage (CC vs. TT: OR = 0.25, 95% CI = 0.12 - 0.54, P=0.0003; C vs. T: OR = 0.69, 95% CI = 0.53-0.89, P=0.006; and CC vs. (TC + TT): OR = 0.26, 95% CI = 0.12-0.56, P=0.0004). CRC patients carrying the rs3737589 CC genotype or C allele were less likely to have stage III/IV tumors than those carrying the rs3737589 TT genotype or T allele. The expression of TP73-AS1 was lower in CRC tissues with the rs3737589 CC genotype compared to those with the TT genotype. Bioinformatics analysis and the luciferase assay revealed that the C allele could promote the binding of miR-3166 and miR-4771 to TP73-AS1. Conclusion: The TP73-AS1 gene rs3737589 polymorphism affecting miRNAs binding is associated with the CRC stage and may serve as a biomarker for predicting CRC progression.

HAND2-AS1 rs2276941 Polymorphism Affecting the Binding of hsa-miR-1275 Is Associated with the Risk of Colorectal Cancer.

Genetic variants in several long noncoding RNA genes have been implicated in the occurrence and development of colorectal cancer (CRC). In this study, we explored the association between HAND2-AS1 gene rs2276941 polymorphism and the risk and clinical stage of CRC. A direct sequencing method was used to detect the rs2276941 polymorphism in 576 CRC patients and 864 healthy individuals. Real-time quantitative PCR technology was used to explore the expression of HAND2-AS1 and hsa-miR-1275 in colorectal tissues with different rs2276941 genotypes. Dual-luciferase reporter assay was used to assess the function of the rs2276941 polymorphism. We found that the rs2276941 polymorphism was associated with a decreased risk of CRC (TT vs. CC, OR = 0.38, 95% CI = 0.16-0.89, p = 0.03; TT vs. [CC+CT], OR = 0.40, 95% CI = 0.17-0.94, p = 0.03). Furthermore, a significant negative correlation was observed between the expression of HAND2-AS1 and hsa-miR-1275 in colorectal tissues with rs2276941 TT genotype. Functional experimental results showed that the rs2276941 T allele might promote the binding of HAND2-AS1 to hsa-miR-1275. The current study results suggested that HAND2-AS1 gene rs2276941 polymorphism affecting the binding of hsa-miR-1275 was associated with CRC risk and might serve as a CRC susceptibility biomarker.

The association of IGF1 rs35767 polymorphism with colorectal cancer risk in the Chinese Han population.

Insulin-like growth factor 1 (IGF1) plays an important role in the development and growth of colorectal cancer (CRC). Hence, potential functional polymorphisms of the IGF1 gene may be involved in CRC risk. This study mainly aimed to assess the association of IGF1 rs35767 polymorphism with CRC risk in the Chinese Han population by a case-control study and a pooled analysis. In a case-control study with 208 CRC patients and 312 healthy individuals, the rs35767 polymorphism was genotyped by DNA sequencing. Furthermore, a pooled analysis of two case-control studies was performed using Stata software. IGF1 rs35767 polymorphism was significantly associated with CRC risk in both a case-control study (AA vs. GG: OR = 2.26, 95% CI = 1.35-3.80, P = 0.003; AA vs. (GG + GA): OR = 2.32, 95% CI = 1.44-3.74, P = 0.001; A vs. G: OR = 1.43, 95% CI = 1.11-1.85, P = 0.007) and a pooled analysis [(GA + AA) versus GG: OR = 1.30, 95% CI = 1.03-1.63, P = 0.03; A versus G: OR = 1.28, 95% CI = 1.08-1.53, P = 0.01]. In addition, the IGF1 rs35767 polymorphism was also significantly associated with the stage of CRC. CRC patients with the rs35767 A allele were more likely to have a high tumor stage. These findings indicated that IGF1 rs35767 polymorphism was linked to CRC risk and tumor stage in the Chinese Han population, and might serve as a valuable biomarker.

Association of TNFAIP8 gene polymorphisms with cancer risk in Chinese population.

As TNFAIP8 plays an important role in the development of cancer, several studies have analyzed the relationship between potential functional polymorphic loci of the TNFAIP8 gene and cancer risk. However, some results were inconsistent. Therefore, the current study aims to systematically assess the relationship between these genetic polymorphisms and cancer risk using a meta-analysis approach. Relevant studies were obtained from CNKI, Embase, Web of Science, and PubMed databases. RevMan software was used to conduct data analysis. The combined analysis containing four studies with 2786 cancer patients and 2550 control individuals indicated that rs11064 polymorphism was not associated with cancer risk. The pooled analysis containing three studies with 950 cancer patients and 1036 control individuals showed that rs1045241 polymorphism was associated with cancer risk in the heterozygous model (CT vs. CC: OR = 1.34, 95%CI = 1.10-1.62, Pz=0.003) and dominant model [(TT + CT) vs. CC: OR = 1.38, 95% CI = 1.15-1.66, Pz=0.0006], but not in other models. The pooled analysis containing two studies 436 cancer patients and 479 control individuals showed that rs1045242 polymorphism was associated with cancer risk in the heterozygous model (AG vs. AA: OR = 1.52, 95%CI = 1.14-2.03, Pz=0.005), dominant model [(GG + AG) vs. AA: OR = 1.56, 95% CI = 1.18-2.07, Pz=0.002] and allelic model (G vs. A: OR = 1.48, 95%CI = 1.16-1.90, Pz=0.002).In conclusion, the current findings suggest that the rs1045241 and rs1045242 polymorphisms located on the TNFAIP8 gene were associated with cancer risk in Chinese population, and may serve as valuable genetic susceptibility markers.

VPS9D1-AS1 gene rs7206570 polymorphism associated with the clinical stage of colorectal cancer and binding with hsa-miR-361-3p.

VPS9D1-AS1 is a long non-coding RNA that can operate as a competitive endogenous RNA and plays an essential role in the occurrence and development of malignancies, including colorectal cancer (CRC). In this study, we investigated whether a putative functional polymorphism (rs7206570) in the VPS9D1-AS1 gene is linked to the risk and clinical stage of CRC. Sanger sequencing method was used to detect the rs7206570 polymorphism in 500 CRC patients and 500 healthy individuals. Quantitative real-time PCR technology was used to detect the expression of VPS9D1-AS1 and hsa-miR-361-3p in colorectal tissues with different rs7206570 genotypes. The dual-luciferase reporter assay was used to examine whether the rs7206570 polymorphism affects hsa-miR-361-3p binding. The rs7206570 polymorphism was not associated with CRC risk, but was associated with the clinical stage of CRC. CRC patients with rs7206570 A allele were less likely to have high-stage CRC. Furthermore, there was a significant negative correlation between the expression of VPS9D1-AS1 and hsa-miR-361-3p in CRC tissues with rs7206570 GG genotype. Dual-luciferase reporter assay showed that the rs7206570 A allele presumably hinders the binding of VPS9D1-AS1 to hsa-miR-361-3p. In conclusion, VPS9D1-AS1 gene rs7206570 polymorphism affecting hsa-miR-361-3p binding was associated with the clinical stage of CRC, which might be able to assist in the preoperative staging of CRC.

Association between HULC rs7763881 and cancer risk: an updated Meta-analysis.

In recent years, several case-control studies have explored the association between the rs7763881 locus polymorphism of the HULC gene and cancer risk, however, the findings have been inconsistent. Therefore, a meta-analysis was conducted to clarify the association. Relevant case-control studies were obtained from CNKI, Embase, Web of Science and PubMed databases. RevMan software was used to perform data analysis. A total of 8 case-control studies containing 4036 cases and 5286 controls were included in the current meta-analysis. The overall analysis results showed no significant association between the rs7763881 locus polymorphism and cancer risk. However, stratified analysis based on cancer type showed that the rs7763881 locus polymorphism was associated with the decreased risk of hepatocellular cancer, colorectal cancer and esophageal cancer. In conclusion, the current findings suggest that the rs7763881 polymorphic loci located on the HULC gene may serve as a biomarker for determining an individual's risk of hepatocellular cancer, colorectal cancer and esophageal cancer.

The Association of MEG3 Gene rs7158663 Polymorphism With Cancer Susceptibility.

Although the association of MEG3 gene rs7158663 polymorphism with cancer susceptibility has been investigated, the findings are inconsistent. The aim of this study was to analyze the association between the rs7158663 polymorphism and cancer susceptibility through a case-control study and meta-analysis. In a case-control study with 430 colorectal cancer (CRC) cases and 445 healthy controls, the rs7158663 polymorphism was genotyped by direct sequencing. STATA software was used to calculate the pooled odds ratio and 95% confidence interval in a meta-analysis including 4,649 cancer cases and 5,590 controls. Both the case-control study and meta-analysis showed that the rs7158663 polymorphism was associated with increased susceptibility to CRC. Individuals carrying the AA or GA genotype were more likely to develop CRC than those carrying the rs7158663 GG genotype. Interestingly, MEG3 expression was significantly lower in colorectal tissues of the AA or GA genotype compared to those of the rs7158663 GG genotype. In addition, the meta-analysis suggested that the rs7158663 polymorphism was also associated with increased susceptibility to breast cancer and gastric cancer. Bioinformatics analysis showed that the rs7158663 A allele contributed to the binding of hsa-miR-4307 and hsa-miR-1265 to MEG3. In conclusion, the current findings suggest that the MEG3 gene rs7158663 polymorphism may serve as a genetic marker for predicting the risk of cancers, such as breast cancer, gastric cancer and CRC. However, the sample size of the current study is still insufficient, especially in the subgroup analysis. Therefore large and well-designed studies are needed to validate our findings.

HMGA2 rs968697 T > C polymorphism is associated with the risk of colorectal cancer.

A genetic polymorphism (rs968697 T > C) in the HMGA2 gene has recently been linked to an increased risk of hepatoblastoma. However, no studies have been conducted to investigate the effect of the polymorphism on the risk of colorectal cancer (CRC). The study aimed to explore whether the rs968697 polymorphism had a significant impact on CRC risk. A total of 500 CRC patients and 500 age and gender matched healthy individuals were genotyped by using the SNaPshot method. Quantitative real-time PCR technology was used to detect the relative expression of the HMGA2 gene in 30 pairs of primary CRC and adjacent non-cancerous tissues. Results: HMGA2 rs968697 polymorphism was significantly associated with CRC risk [CC vs. TT: OR = 0.20, 95%CI = 0.06-0.70, P = 0.01; (CC + CT) vs. TT: OR = 0.71, 95%CI = 0.53-0.96, P = 0.02; CC vs. (CT + TT): OR = 0.21, 95%CI = 0.06-0.73, P = 0.01; C vs. T: OR = 0.67, 95%CI = 0.51-0.89, P < 0.01]. The analysis based on tumor stage indicated that the CRC patients with HMGA2 rs968697 C allele were less likely to have high-stage tumors. Furthermore, the genotype-tissue expression analysis revealed that the rs968697 CC genotype was linked to the low expression of HMGA2 gene. The in silico analysis revealed that the rs968697 polymorphism in the promoter region of the HMGA2 gene could influence transcription factor binding, including ATF6, DBP, CDPCR3, DR3, NRSF, PAX8, PPARA, SZF11, TAXCREB and POLR2A. In conclusion, our findings suggested that the HMGA2 rs968697 polymorphism was linked to CRC risk and could be used as a biomarker to detect CRC risk.

Identification of key genes associated with lung adenocarcinoma by bioinformatics analysis.

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, comprising around 40% of all lung cancer. Until now, the pathogenesis of LUAD has not been fully elucidated. In the current study, we comprehensively analyzed the dysregulated genes in lung adenocarcinoma by mining public datasets. Two sets of gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. The dysregulated genes were identified by using the GEO2R online tool, and analyzed by R packages, Cytoscape software, STRING, and GPEIA online tools. A total of 275 common dysregulated genes were identified in two independent datasets, including 54 common up-regulated and 221 common down-regulated genes in LUAD. Gene Ontology (GO) enrichment analysis showed that these dysregulated genes were significantly enriched in 258 biological processes (BPs), 27 cellular components (CCs), and 21 molecular functions (MFs). Furthermore, protein-protein interaction (PPI) network analysis showed that PECAM1, ENG, KLF4, CDH5, and VWF were key genes. Survival analysis indicated that the low expression of ENG was associated with poor overall survival (OS) of LUAD patients. The low expression of PECAM1 was associated with poor OS and recurrence-free survival of LUAD patients. The cox regression model developed based on age, tumor stage, ENG, PECAM1 could effectively predict 5-year survival of LUAD patients. This study revealed some key genes, BPs, CCs, and MFs involved in LUAD, which would provide new insights into understanding the pathogenesis of LUAD. In addition, ENG and PECAM1 might serve as promising prognostic markers in LUAD.

Identification of lnc RNAs Related to Prognosis of Patients With Colorectal Cancer.

The purpose of this study was to identify long noncoding RNAs (lncRNAs) related to prognosis of patients with colorectal cancer (CRC) and develop a prognostic prediction model for CRC. Transcriptome data and survival information of CRC patients were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) between CRC and normal colorectal tissues were identified by the edgeR package. The association of DElncRNAs expression with prognosis of CRC patients was analyzed by the survival package. A nomogram predicting 3- and 5- year overall survival of CRC patients was drawn by the rms package. A total of 1046 DElncRNAs were identified, including 271 down-regulated and 775 up-regulated lncRNAs in CRC. Multivariate Cox regression analysis showed 10 lncRNAs related to the prognosis of CRC patients. Thereinto high expression of AC004009.1, LHX1-DT, ELFN1-AS1, AL136307.1, AC087379.2, RBAKDN and AC078820.1 was associated with poorer prognosis of CRC patients. High expression of LINC01055, AL590483.1 and AC008514.1 was associated with better prognosis of CRC patients. Furthermore, the risk score model developed based on the 10 lncRNAs could effectively predict overall survival of CRC patients. In conclusion, 10 prognostic biomarkers for CRC were identified, which would be helpful to understand the role of lncRNAs in CRC progression.

Meta-analysis of the association between MALAT1 rs619586 A>G polymorphism and cancer risk.

OBJECTIVE: This study aimed to systematically assess the effect of the metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long noncoding RNA rs619586 polymorphism on cancer risk. METHODS: We conducted a literature search of the PubMed, Embase, and China National Knowledge Internet databases to identify relevant studies, and calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the retrieved studies using RevMan software. RESULTS: Nine eligible studies including 5968 cases and 7439 controls were included in the meta-analysis. The pooled results showed that MALAT1 rs619586 polymorphism was significantly associated with cancer risk [(AG + GG) vs. AA: OR = 0.88; GG vs. (AG + AA): OR = 0.64; GG vs. AA: OR = 0.63; AG vs. AA: OR = 0.91; G vs. A: OR = 0.87]. However, subgroup analyses based on ethnicity and cancer type showed significant associations between MALAT1 rs619586 polymorphism and cancer risk in Asians and for cancers other than hepatocellular carcinoma, but not for Caucasians and hepatocellular carcinoma. CONCLUSIONS: MALAT1 rs619586 polymorphism may play a role in cancer risk. However, further studies are needed to confirm these findings.

Novel PYGL mutations in Chinese children leading to glycogen storage disease type VI: two case reports.

BACKGROUND: PYGL mutations can cause liver phosphorylase deficiency, resulting in a glycogenolysis disorder, namely, glycogen storage disease (GSD) VI. The disease is rarely reported in the Chinese population. GSD VI is mainly characterized in untreated children by hepatomegaly, growth retardation and elevated liver transaminases. CASE PRESENTATION: In this study, we report two GSD VI patients with growth retardation and abnormal liver function. There was no obvious hepatomegaly for one of them. Whole exome sequencing (WES) combined with copy number variation analysis was performed. We found a novel homozygous gross deletion, c.1621-258_2178-23del, including exons 14-17 of PYGL in patient 1. The exons 14-17 deletion of PYGL resulted in an in-frame deletion of 186 amino acids. Compound heterozygous mutations of PYGL were identified in patient 2, including a novel missense mutation c.1832C > T/p.A611V and a recurrent nonsense mutation c.280C > T/p.R94X. After treatment with uncooked cornstarch (UCS) 8 months for patient 1 and 13 months for patient 2, the liver transaminases of both patients decreased to a normal range and their stature was improved. However, patient 1 still showed mild hypertriglyceridemia. CONCLUSIONS: We describe two GSD VI patients and expand the spectrum of PYGL mutations. Patient 1 in this study is the first GSD VI case that showed increased transaminases without obvious hepatomegaly due to a novel homozygous gross deletion of PYGL identified through WES.

High Detection Rate of Copy Number Variations Using Capture Sequencing Data: A Retrospective Study.

BACKGROUND: Capture sequencing (CS) is widely applied to detect small genetic variations such as single nucleotide variants or indels. Algorithms based on depth comparison are becoming available for detecting copy number variation (CNV) from CS data. However, a systematic evaluation with a large sample size has not been conducted to evaluate the efficacy of CS-based CNV detection in clinical diagnosis. METHODS: We retrospectively studied 3010 samples referred to our diagnostic laboratory for CS testing. We used 68 chromosomal microarray analysis-positive samples (true set [TS]) and 1520 reference samples to build a robust CS-CNV pipeline. The pipeline was used to detect candidate clinically relevant CNVs in 1422 undiagnosed samples (undiagnosed set [UDS]). The candidate CNVs were confirmed by an alternative method. RESULTS: The CS-CNV pipeline detected 78 of 79 clinically relevant CNVs in TS samples, with analytical sensitivity of 98.7% and positive predictive value of 49.4%. Candidate clinically relevant CNVs were identified in 106 UDS samples. CNVs were confirmed in 96 patients (90.6%). The diagnostic yield was 6.8%. The molecular etiology includes aneuploid (n = 7), microdeletion/microduplication syndrome (n = 40), and Mendelian disorders (n = 49). CONCLUSIONS: These findings demonstrate the high yield of CS-based CNV. With further improvement of our CS-CNV pipeline, the method may have clinical utility for simultaneous evaluation of CNVs and small variations in samples referred for pre- or postnatal analysis.

Identification of Genes Related to Clinicopathological Characteristics and Prognosis of Patients with Colorectal Cancer.

The aim of this study was to identify genes with clinical significance in colorectal cancer (CRC). Gene expression profiles of 585 CRC tissues and 61 normal colorectal tissues from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to identify differentially expressed genes (DEGs) between CRC and normal colorectal tissues. DAVID and KOBAS tools were used to explore Gene Ontology (GO) and KEGG pathways enriched by DEGs, respectively. In addition, TCGA data sets were also used to identify prognostic factors and develop a prognostic prediction model for CRC. A total of 353 DEGs including 117 upregulated and 236 downregulated genes in CRC were identified based on GSE32323 data set. These DEGs were significantly enriched in the biological process related to the regulation of cell proliferation and 50 signaling pathways, such as "TGF-beta signaling pathway," "Wnt signaling pathway," and "Jak-STAT signaling pathway." GCG, ADH1B, SLC4A4, ZG16, and CLCA4 were the top five downregulated in CRC. FOXQ1, LGR5, CLDN1, KRT23, and DPEP1 were the top five upregulated in CRC. KRT23 expression could affect tumor stage and regional lymph node metastasis in CRC patients. FOXQ1 expression could affect tumor distant metastasis in CRC patients. Survival analysis indicated that SLC4A4 expression was associated with the prognosis of CRC patients. Prognostic prediction model developed based on age, tumor stage, and SLC4A4 expression exhibited an efficient performance in predicting 1-, 3-, and 5-year overall survival of CRC patients. In conclusion, the current study identified several genes and pathways related to CRC, which provided new insight in understanding molecular mechanism of tumorigenesis and development of CRC.