Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk.

The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.

Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention and intervention.

Identifying risk protein targets and their therapeutic drugs is crucial for effective cancer prevention. Here, we conduct integrative and fine-mapping analyses of large genome-wide association studies data for breast, colorectal, lung, ovarian, pancreatic, and prostate cancers, and characterize 710 lead variants independently associated with cancer risk. Through mapping protein quantitative trait loci (pQTL) for these variants using plasma proteomics data from over 75,000 participants, we identify 365 proteins associated with cancer risk.

Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants That Confer Risk for Breast Cancer.

Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium.

A large-scale microRNA transcriptome-wide association study identifies two susceptibility microRNAs, miR-1307-5p and miR-192-3p, for colorectal cancer risk.

Transcriptome-wide association studies (TWAS) have identified many putative susceptibility genes for colorectal cancer (CRC) risk. However, susceptibility miRNAs, critical dysregulators of gene expression, remain unexplored. We genotyped DNA samples from 313 CRC East Asian patients and performed small RNA sequencing in their normal colon tissues distant from tumors to build genetic models for predicting miRNA expression.

Development of a Facile Lysosome-Targeting Nitric Oxide Fluorescent Probe Based on a Novel Reaction Mechanism.

As a ubiquitous signal molecule in biosystems, nitric oxide (NO) plays an important role in many physiological and pathological processes. Therefore, it is of great significance to detect NO in organisms for the study of related diseases. Currently, a variety of NO fluorescent probes have been developed based on several types of reaction mechanisms.

The putative oncogenic role of WDTC1 in colorectal cancer.

Microsatellite instability (MSI) is detected in approximately 15% of colorectal cancers (CRCs). WD40 and tetratricopeptide repeats 1 (WDTC1) is frequently mutated in MSI CRC, indicating that it may contribute to CRC development. However, the functional evidence of the role of WDTC1 in CRC development remains unknown.

TBX1 functions as a putative oncogene of breast cancer through promoting cell cycle progression.

We have previously identified a genetic variant, rs34331122 in the 22q11.21 locus, as being associated with breast cancer risk in a genome-wide association study. This novel variant is located in the intronic region of the T-box transcription factor 1 (TBX1) gene.

Genome-wide association study identifies new loci associated with noise-induced tinnitus in Chinese populations.

Background: Tinnitus is an auditory phantom sensation in the absence of an acoustic stimulus, which affects nearly 15% of the population. Excessive noise exposure is one of the main causes of tinnitus. To now, the knowledge of the genetic determinants of susceptibility to tinnitus remains limited.

Clinicopathological Features and Survival of Signet-Ring Cell Carcinoma and Mucinous Adenocarcinoma of Right Colon, Left Colon, and Rectum.

Histological subtype plays an important role in the different clinical characteristics and survival outcomes of patients with colorectal carcinoma (CRC). However, in previous studies, the influences of tumor locations and tumor stages have not been strictly controlled. This study focused on the assessment of the prognostic value of each histological subtype in different tumor locations and tumor stages of CRC.

Metastasis Prevalence and Survival of Patients with T1-2 Gastric Neuroendocrine Tumor Treated with Endoscopic Therapy and Surgery.

Background And Aim: The selection criteria and long-term outcomes of endoscopic therapy (ET) for gastric neuroendocrine tumors (G-NETs) remain controversial.

Methods: Using Surveillance, Epidemiology, and End Results (SEER) Program database, we assessed the prevalence of metastasis of early G-NETs and long-term outcomes of ET in G-NET patients with good/moderate differentiation and no muscularis propria (MP) involvement.

Results: A total of 2207 patients with stage T1 and T2 G-NETs were included.

Characterization of structural variation in Tibetans reveals new evidence of high-altitude adaptation and introgression.

Background: Structural variation (SV) acts as an essential mutational force shaping the evolution and function of the human genome. However, few studies have examined the role of SVs in high-altitude adaptation and little is known of adaptive introgressed SVs in Tibetans so far.

Results: Here, we generate a comprehensive catalog of SVs in a Chinese Tibetan (n = 15) and Han (n = 10) population using nanopore sequencing technology.

Functional Genomic Analyses of the 21q22.3 Locus Identifying Functional Variants and Candidate Gene for Breast Cancer Risk.

We previously identified a locus at 21q22.3, tagged by the single nucleotide polymorphism (SNP) rs35418111, being associated with breast cancer risk at a genome-wide significance level; however, the underlying causal functional variants and gene(s) responsible for this association are unknown. We performed functional genomic analyses to identify potential functional variants and target genes that may mediate this association.

Computational fluid dynamics simulation of time-resolved blood flow in Budd-Chiari syndrome with inferior vena cava stenosis and its implication for postoperative efficacy assessment.

Background: This study aimed to adopt computational fluid dynamics to simulate the blood flow dynamics in inferior vena cava stenosis based on time-dependent patient-specific models of Budd-Chiari syndrome as well as a normal model. It could offer valuable references for a retrospective insight into the underlying mechanisms of Budd-Chiari syndrome pathogenesis as well as more accurate evaluation of postoperative efficacy.

Methods: Three-dimensional inferior vena cava models of Budd-Chiari syndrome patient-specific (preoperative and postoperative) and normal morphology model were reconstructed as per magnetic resonance images using Simpleware.

Genome-wide association study identifies 7q11.22 and 7q36.3 associated with noise-induced hearing loss among Chinese population.

Noise-induced hearing loss (NIHL) seriously affects the life quality of humans and causes huge economic losses to society. To identify novel genetic loci involved in NIHL, we conducted a genome-wide association study (GWAS) for this symptom in Chinese populations. GWAS scan was performed in 89 NIHL subjects (cases) and 209 subjects with normal hearing who have been exposed to a similar noise environment (controls), followed by a replication study consisting of 53 cases and 360 controls.

miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer.

Our previous study demonstrated that miR-124 was downregulated in colorectal cancer (CRC) compared with normal mucosa, and the downregulated expression of miR-124 was an independent prognostic factor in CRC patients. However, the function of miR-124 in CRC patients treated with chemotherapy is currently unclear. The aim of this study was to determine the miR-124 expression and its regulative role in oxaliplatin (L-OHP)-based chemotherapy of CRC patients.

Prognostic impact of lymph node status in patients after total pancreatectomy for pancreatic ductal adenocarcinoma: A strobe-compliant study.

The optimal number of examined lymph nodes (ELN) for staging and impact of nodal status on survival following total pancreatectomy (TP) for pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of this study was to evaluate the prognostic impact of different lymph node status after TP for PDAC.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients who underwent TP for PDAC from 2004 to 2015.

Disparities in survival by stage after surgery between pancreatic head and body/tail in patients with nonmetastatic pancreatic cancer.

Background: The survival of pancreatic cancer patients with lesions in different locations is unclear. In addition, the different surgery types for nonmetastatic pancreatic head cancer (PHC) or body/tail cancer (PBTC) have different prognostic influences. We analyzed the association by stage between tumor location (head vs.

Impact of different surgical procedures on survival outcomes of patients with adenocarcinoma of pancreatic neck.

Background: The only curative treatment for pancreatic adenocarcinoma is radical surgical resection. Because of the special anatomic features of pancreatic neck, the selection of optimal surgical procedure for treatment of adenocarcinoma of pancreatic neck has always been a dilemma for surgeons. In this paper, we aim to investigate whether different surgical procedures can affect prognosis in the patient with adenocarcinoma of pancreatic neck.

The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer.

Purpose: To explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.

Methods And Materials: Rho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established using the CRISPR/Cas9 system.

Association of MCP-1 promoter polymorphism with susceptibility to nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is prevalent among populations from southern China and is influenced by both genetic and environmental risk factors. The monocyte chemoattractant protein-1 (MCP-1), a member of cysteine-cysteine chemokine family, plays critical roles in cancers. A polymorphism within the MCP-1 promoter, rs1024611, has been shown to be significantly associated with the risk of several cancers.

Genome-Wide Association Study Identifies a New Locus at 7q21.13 Associated with Hepatitis B Virus-Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In China, chronic hepatitis B virus (HBV) infection remains the major risk factor for HCC. In this study, we performed a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci contributing to susceptibility to HBV-related HCC.

CRISPR/Cas9-mediated targeted chromosome elimination.

Background: The CRISPR/Cas9 system has become an efficient gene editing method for generating cells carrying precise gene mutations, including the rearrangement and deletion of chromosomal segments. However, whether an entire chromosome could be eliminated by this technology is still unknown.

Results: Here we demonstrate the use of the CRISPR/Cas9 system to eliminate targeted chromosomes.