Biomarkers and Genomic Medicine最新文献

Adiponectin is considered a modulator of glucose metabolism. Hypoadiponectinemia was reported to be associated with glucose metabolism and metabolic syndrome, and had been found in patients with hepatitis B virus (HBV) and hepatitis C virus infections. However, little is known about the role of adiponectin in patients with HBV infection. Fifty-five patients with HBV infection and 52 healthy individuals were included in this study. We found that serum adiponectin was significantly lower in patients with HBV infection. We also found that HBV-infected patients with hemoglobin A1C ≥6.5% had a lower adiponectin level than those with hemoglobin A1C <6.5%. In conclusion, hypoadiponectinemia occurs in patients with HBV infection, and adiponectin may play a role in the pathogenesis of glucose metabolism in these patients.

The diversity of genomic variations exists among different ethnic populations. Information on population-specific genomic variants provides important insights to link between genotypes and phenotypes. To facilitate genomic medicine research, this study aims to detect and characterize sequence variations enriched in the coding regions of the genome in the Chinese population residing in Taiwan. DNAs from 11 unrelated Taiwanese individuals were enriched for coding regions (i.e., exome) and followed by deep sequencing. Approximately 30 Gb of high-quality data from massively parallel sequencing was obtained. On average, ∼60% of the total reads were uniquely mapped to the human reference genome and overall 97% of the target regions were covered by sequence reads, resulting in an average enrichment fold relative to target size of ∼50-fold. Comprehensive variant detection and analysis were performed with various in-house established bioinformatics pipelines, and information for different types of variations including single nucleotide variants, short insertions and deletions, and copy number variations was collected. The sequence variations were crossed with variants in the public databases to identify ethnic-specific variants. To study the impact of sequence variations that are enriched in the Taiwanese Han population, variants that are present in at least two exomes (i.e., minor allele frequency >9%) were further annotated. Overall, we detected 308 loss-of-function variants that belong to 291 genes in the Taiwanese Han Exome Sequencing dataset. Functional annotation revealed a significant pathological influence of these loss-of-function-associated genes in the risk of various human diseases including lung cancer. This is the first NGS (next-generation sequencing)-generating dataset to comprehensively report coding sequence variants in the Taiwanese Han population. Given that the Taiwanese Han population is the Han Chinese residing in Taiwan, it is normally underrepresented in population-genetics studies. We believe the study will contribute valuable information that will have an impact on medical as well as population genetics.

Aloin, the major anthraquinone in aloe exudates and gels, has been shown to be an effective antioxidant and anti-inflammatory agent. We studied the antitumor effects of aloin in human non-small cell lung cancer cells. The treatment of lung cancer cells with aloin suppressed cell growth in a time- and concentration-dependent manner. Aloin-induced apoptosis also showed a concentration-dependent behavior when studied by flow cytometry. In addition, autophagy occurred after treatment with aloin. Taken together, our data demonstrate that aloin induces apoptosis and autophagy in human lung cancer cells. Aloin is therefore a potential therapeutic agent for human lung cancer and is worthy of further investigation.

Radiotherapy (RT) plays a much more important role in the treatment of colorectal cancer when it can be used to reduce the size of a tumor prior to the local excision of the cancer. In order to find other factors possibly related to radiosensitivity, we evaluated the relationships between circulating blood cell counts and RT effects. In 81 cases of rectal cancer, we examined white blood cell and platelet counts, as well as hemoglobin (Hb) levels, prior to RT, and also investigated their associations with the treatment response rate and with other clinicopathological factors. The patients with anemia had significantly worse RT responses, whereas patients with high white blood cell counts (≥7400/μL) showed better responses (p < 0.001). Cancer patients with low Hb levels do not respond as well to RT as nonanemic patients (p = 0.018). In colorectal cancer patients, white blood cell counts and Hb levels have a significant impact on the responsiveness to RT.

Colorectal cancer is a common gastrointestinal malignancy. Radiation combined with chemotherapy (also known as concurrent chemoradiotherapy or CCRT) is often used prior to surgery for treating severe cases of colorectal cancer. However, responses of individual tumors to CCRT differ. Therefore, in light of the variability in radiation sensitivity among different tumors, identifying the factors that can be applied to predict CCRT efficacy prior to treatment will aid in making decisions regarding an appropriate treatment strategy. In the present study, we used a gene chip to analyze the expression of candidate genes in the tumor cells of colorectal cancer patients prior to and after treatment with CCRT, in order to identify molecular markers that can predict the efficacy of CCRT. First, we selected a total of 15 CCRT candidate genes based on the results of previous studies, which used the microarray method to select CCRT response-related genes that were also related to tumor malignancy. We collected preoperative CCRT tumor tissues from 17 colorectal cancer patients for whom the efficacy of CCRT had already been determined and used gene chips to analyze the expression of CCRT-related genes in the tissues of these patients. We then compared the results for the expression of CCRT-related genes with those for the clinical efficacy of CCRT. Of the 15 candidate genes, five genes (CK-20, ELAVL4, EV12B, TM4SF3, and ATPA2) were upregulated in >29.4% and one gene (MET) was downregulated in 23.5% of the total patients after treatment with CCRT, indicating that these genes may be potential predictive markers for CCRT efficacy.

MicroRNAs (miRNAs) are short noncoding RNA molecules involved in the regulation of carcinogenesis. Tumor-derived miRNAs will be released into the circulation, and these miRNAs, also known as circulating miRNAs, have stable properties in plasma and serum. Thus miRNAs have been suggested as a potential biomarker for cancer diagnosis. The aim of this study was to develop a miRNA biochip platform. First, we used three types of reverse transcription (RT) primers; we constructed the miRNA-containing poly(A) tail and used RT primer oligo(dT) to make the complementary DNA (cDNA), and we also designed a linear-form RT primer and a stem-loop RT primer to synthesize cDNA. Second, we selected 11 candidate miRNAs related to colorectal cancer (CRC) from our previous studies and then designed the probes based on the sequence of the candidate miRNAs and constructed a miRNA biochip. miRNAs were extracted from CRC cell line SW620 and were detected by enzymatic biochip assay. According to the results, we found that this miRNA biochip can effectively detect the miRNAs by using a specific stem-loop RT primer to synthesize cDNA. In the future, we will design more oligonucleotides for miRNA detection and also evaluate the consistency between the results of the miRNA biochip and quantitative real-time polymerase chain reaction (PCR).