C and G are frequently mutated into T and A in coding regions of human genes.

Nucleotide mutations in human genes have long been a hot subject for study because some of them may lead to severe human diseases. Understanding the general mutational process and evolutionary trend of human genes could help answer such questions as why certain diseases occur and what challenges we face in protecting human health. In this study, we conducted statistics on 89,895 single-nucleotide variations identified in coding regions of 18,339 human genes. The results show that C and G are frequently mutated into T and A in human genes. C/G (C or G)-to-T/A mutations lead to reduction of hydrogen bonds in double-stranded DNA because C-G and T-A base pairs are maintained by three and two hydrogen bonds respectively. C-to-T and G-to-A mutations occur predominantly in human genes because they not only reduce hydrogen bonds but also belong to transition mutation. Reduction of hydrogen bonds could reduce energy consumption not only in separating double strands of mutated DNA for transcription and replication but also in disrupting stem-loop structure of mutated mRNA for translation. It is thus considered that to reduce hydrogen bonds (and thus to reduce energy consumption in gene expression) is one of the driving forces for nucleotide mutation. Moreover, codon mutation is positively correlated to its content, suggesting that most mutations are not targeted on changing any specific codons (amino acids) but are merely for reducing hydrogen bonds. Our study provides an example of utilizing single-nucleotide variation data to infer evolutionary trend of human genes, which can be referenced to conduct similar studies in other organisms.

Growth, development, and host preference of Histiostoma feroniarum (Acaridida: Histiostomatidae): effects of temperature and types of mushroom cultivar.

One of the most common harmful mites in edible fungi is Histiostoma feroniarum Dufour (Acaridida: Histiostomatidae), a fungivorous astigmatid mite that feeds on hyphae and fruiting bodies, thereby transmitting pathogens. This study examined the effects of seven constant temperatures and 10 types of mushrooms on the growth and development of H. feroniarum, as well as its host preference. Developmental time for the total immature stages was significantly affected by the type of mushroom species, ranging from 4.3 ± 0.4 days (reared on Pleurotus eryngii var. tuoliensis Mou at 28°C) to 17.1 ± 2.3 days (reared on Auricularia polytricha Sacc. at 19°C). The temperature was a major factor in the formation of facultative heteromorphic deutonymphs (hypopi). The mite entered the hypopus stage when the temperature dropped to 16°C or rose above 31°C. The growth and development of this mite were significantly influenced by the type of species and variety of mushrooms. Moreover, the fungivorous astigmatid mite preferred to feed on the 'Wuxiang No. 1' strain of Lentinula edodes (Berk.) Pegler and the 'Gaowenxiu' strain of P. pulmonarius (Fr.) Quél., with a shorter development period compared with that of feeding on other strains. These results therefore quantify the effect of host type and temperature on fungivorous astigmatid mite growth and development rates, and provide a reference for applying mushroom cultivar resistance to biological pest control.

Phylogenetic analysis of achaete-scute complex genes in metazoans.

Achaete-scute complex (ASC) genes play essential roles in regulating neurogenesis of metazoans. Various metazoan species have greatly different numbers of genes in ASCa, ASCb and ASCc families. To explore evolutionary mechanisms of metazoan ASC genes, Blast (basic local alignment search tool) searches and phylogenetic analyses were conducted to identify ASC genes in metazoan species and to infer phylogenetic relationship between various ASC genes. As a result, 2784 ASC genes were identified in 804 metazoan species. The phylogenetic tree constructed using 1237 unique bHLH motifs shows that metazoan ASCa, ASCb and ASCc families contain six (a1-a6), five (b1-b5) and three (c1-c3) bHLH genes, respectively. Further phylogenetic analyses suggest that ASC genes in metazoans are derived from a primitive c gene, those in insects are derived from c2 gene, and those in chordates are derived from a2 and a3 genes. Data of gene linkage demonstrate that insect a6 is derived from a4 but not from a5, and chordate a2 is ancestral to b5 only, whilst a3 is ancestral to both b3 and b5. It is concluded that current ASC gene families in metazoans were established through a series of sub- and/or neo-functionalization to duplicated ancestral ASC gene(s). These results provide good references for exploring evolutionary mechanisms of other bHLH genes in metazoans. Besides, gene subtyping is considered as an efficient method for evolutionary studies on closely related homologous genes.

TA, GT and AC are significantly under-represented in open reading frames of prokaryotic and eukaryotic protein-coding genes.

Genomes can be considered a combination of 16 dinucleotides. Analysing the relative abundance of different dinucleotides may reveal important features of genome evolution. In present study, we conducted extensive surveys on the relative abundances of dinucleotides in various genomic components of 28 bacterial, 20 archaean, 19 fungal, 24 plant and 29 animal species. We found that TA, GT and AC are significantly under-represented in open reading frames of all organisms and in intergenic regions and introns of most organisms. Specific dinucleotides are of greatly varied usage at different codon positions. The significantly low representations of TA, GT and AC are considered the evolutionary consequences of preventing formation of pre-mature stop codons and of reducing intron-splicing options in candidate primary mRNA sequences. These data suggest that a reduction of TA and GT occurred on both strands of the DNA sequence at an early stage of de novo gene birth. Interestingly, GT and AC are also significantly under-represented in current prokaryotic genomes, suggesting that ancient prokaryotic protein-coding genes might have contained introns. The greatly varied usages of specific dinucleotides at different codon positions are considered evolutionary accommodations to compensate the unavailability of specific codons and to avoid formation of pre-mature stop codons. This is the first report presenting data of dinucleotide relative abundance to indicate the possible existence of spliceosomal introns in ancient prokaryotic genes and to hypothesize early steps of de novo gene birth.

Identification and Phylogenetic Analysis of Basic Helix-Loop-Helix Genes in the Diamondback Moth.

Basic helix-loop-helix (bHLH) transcription factors play essential roles in regulating eukaryotic developmental and physiological processes such as neuron generation, myocyte formation, intestinal tissue development, and response to environmental stress. In this study, the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), genome was found to encode 52 bHLH genes. All 52 P. xylostella bHLH (PxbHLH) genes were classified into correspondent bHLH families according to their orthology with bHLHs from fruit fly and other insect species. Among these 52 PxbHLH genes, 19 have been annotated consistently with our classification in GenBank database. The remaining 33 PxbHLH genes are either annotated as general bHLH genes or as hypothetical genes. Therefore, our data provide useful information for updating annotations to PxbHLH genes. P. xylostella has four stem cell leukemia (SCL) genes (one of them has three copies), two Dys genes, two copies of MyoR, Mitf, and Sima genes, and three copies of Sage genes. Further studies may be conducted to elucidate functions of these specific bHLH genes in regulating P. xylostella growth and development.

Genome-wide identification and analysis of basic helix-loop-helix domains in dog, Canis lupus familiaris.

The basic helix-loop-helix (bHLH) domain is a highly conserved amino acid motif that defines a group of DNA-binding transcription factors. bHLH proteins play essential regulatory roles in a variety of biological processes in animal, plant, and fungus. The domestic dog, Canis lupus familiaris, is a good model organism for genetic, physiological, and behavioral studies. In this study, we identified 115 putative bHLH genes in the dog genome. Based on a phylogenetic analysis, 51, 26, 14, 4, 12, and 4 dog bHLH genes were assigned to six separate groups (A-F); four bHLH genes were categorized as ''orphans''. Within-group evolutionary relationships inferred from the phylogenetic analysis were consistent with positional conservation, other conserved domains flanking the bHLH motif, and highly conserved intron/exon patterns in other vertebrates. Our analytical results confirmed the GenBank annotations of 89 dog bHLH proteins and provided information that could be used to update the annotations of the remaining 26 dog bHLH proteins. These data will provide good references for further studies on the structures and regulatory functions of bHLH proteins in the growth and development of dogs, which may help in understanding the mechanisms that underlie the physical and behavioral differences between dogs and wolves.

Regression of fragmented QRS complex: a marker of electrical reverse remodeling in cardiac resynchronization therapy.

BACKGROUND: Fragmented QRS (fQRS) marks inhomogeneous activation and asynchronous cardiac contraction. It has been proved that cardiac resynchronization therapy (CRT) could reverse geometrical remodeling as well as correct electrical dyssynchrony. We aimed to investigate whether fQRS changed corresponding to the therapeutic response to CRT. METHODS: Patients who underwent de novo CRT implantation previously and had ≥1 follow-up between August 2012 and September 2013 in our hospital were investigated. Intrinsic electrocardiogram was recorded and fQRS in any lead was calculated. Response to CRT was defined as absolute improvement in left ventricular ejection fraction by ≥10% or by improvement >1 New York Heart Association class and without heart failure hospitalization. RESULTS: A total of 75 patients (48 male, mean ages, 61 ± 9 years) were included in this study. At a median follow-up of 13 months, 57 patients had response to CRT. Responders had narrowed QRS (from 167 ± 23 ms to 158 ± 19 ms, P = 0.003) and reduced fQRS post-CRT. Nonresponders had QRS prolonging (from 151 ± 26 ms to 168 ± 16 ms, P = 0.033) and increase in fQRS. Eleven of 12 patients with reduced fQRS were responders and 8 of 12 with increased fQRS were nonresponders. Both changes in QRS and fQRS correlated strongly with CRT response (r = 0.389, P = 0.001 and r = 0.403, P = 0.000, respectively). Reduction of fQRS in ≥1 leads had high specificity (95%) in association to responders, though in low sensitivity (19%). CONCLUSIONS: The changes in fQRS associated with therapeutic response to CRT. Regression of fQRS could be a maker of electrical reverse remodeling following CRT.

Organic anion-transporting polypeptides contribute to the hepatic uptake of berberine.

1. The purpose of this study was to investigate the mechanism of hepatic uptake of berberine. Berberine accumulation in hepatocytes was found to be highly dependent on active uptake, which could not be explained by liver organic cation transporter (OCT) alone. 2. Our studies indicated that berberine uptake was significantly suppressed by rifampicin, cyclosporine A and glycyrrhizic acid, which act as specific inhibitors of different Oatp isoforms (Oatp1a1, Oatp1a4 and Oatp1b2) in rat hepatocytes. The combination of OCT and OATP inhibitors further reduced berberine accumulation in both rat and human hepatocytes. The uptake of berberine could be increased in human HEK293-OATP1B3 but not in OATP1B1-transfected HEK 293 cells. 3. Rifampicin could reduce the berberine liver extraction ratio (ER) and double its concentration in the effluent in isolated rat livers. Further in vivo study indicated that berberine plasma exposure could be significantly increased by co-administration of the OATP inhibitor rifampicin or the substrate rosuvastatin. 4. In conclusion, this study demonstrated that both OCT and OATP contribute to the accumulation of berberine in the liver. OATPs may have important roles in berberine liver disposition and potential clinically relevant drug--drug interactions.

A genome-wide identification and classification of basic helix-loop-helix genes in the jewel wasp, Nasonia vitripennis (Hymenoptera: Pteromalidae).

Basic helix-loop-helix (bHLH) proteins are highly conserved DNA-binding transcription factors of a large superfamily. Animal bHLH proteins play important regulatory roles in various developmental processes such as neurogenesis, myogenesis, heart development, and hematopoiesis. The jewel wasp (Nasonia vitripennis) is a good model organism of hymenoptera insects for studies of developmental and evolutionary genetics. In this study, we identified 48 bHLH genes in the genome of N. vitripennis. According to phylogenetic analysis, based on N. vitripennis bHLH (NvbHLH) motif sequences and structural domain distribution in their full-length protein sequences, the identified NvbHLH genes were classified into 36 bHLH families with 19, 12, 9, 1, 6, and 1 member(s) in groups A, B, C, D, E, and F, respectively. Our classification to the identified NvbHLH family members confirms GenBank annotations for 21 of the 48 NvbHLH proteins and provides useful information for further characterization and annotation of the remaining 27 NvbHLH proteins. Compared to other insect species, N. vitripennis has the lowest number of bHLH family members. No NvbHLH members have been found in the families Net, MyoRa, and PTFa, while all other insect species have at least one member in each of the families. These data constitute a solid basis for further investigations into the functions of bHLH proteins in developmental regulation of N. vitripennis.

Association of body mass index with cardiac reverse remodeling and long-term outcome in advanced heart failure patients with cardiac resynchronization therapy.

BACKGROUND: The effect of adiposity on response to cardiac resynchronization therapy (CRT) and long-term outcome in patients undergoing CRT has not been previously reported. This study assessed the impact of baseline body mass index (BMI) on cardiac reverse remodeling and prognosis following CRT. METHODS AND RESULTS: A total of 247 CRT patients were included and divided into 4 groups according to baseline BMI. During 6-month follow-up, overweight and obese patients (BMI, 24-28 kg/m(2), ≥28 kg/m(2), respectively) were inclined to have better clinical and echocardiographic improvements (P<0.05) as well as higher response rate (P<0.001) than underweight and normal weight patients (BMI, <18.5 kg/m(2), 18.5-24 kg/m(2), respectively). During long-term follow-up, overweight and obese patients had lower all-cause mortality (P=0.015) and combined endpoint of death or HF hospitalizations (P=0.001) than underweight and normal weight patients. Compared with normal weight patients, underweight patients had a 2.29-fold increase in risk of combined endpoint events whereas overweight and obese patients had a reduction in the risk of death (66% and 58%, respectively) and combined endpoint events (52% and 38%, respectively). CONCLUSIONS: Patients with obesity and overweight derived more benefit from CRT. Higher BMI was independently associated with better clinical outcome in CRT patients.

A genome-wide identification of basic helix-loop-helix motifs in Pediculus humanus corporis (Phthiraptera: Pediculidae).

Basic helix-loop-helix (bHLH) proteins comprise a large superfamily of transcription factors, which are involved in the regulation of various developmental processes. bHLH family members are widely distributed in various eukaryotes including yeast, fruit fly, zebrafish, mouse, and human. In this study, we identified 55 bHLH motifs encoded in genome sequence of the human body louse, Pediculus humanus corporis (Phthiraptera: Pediculidae). Phylogenetic analyses of the identified P. humanus corporis bHLH (PhcbHLH) motifs revealed that there are 23, 11, 9, 1, 10, and 1 member(s) in groups A, B, C, D, E, and F, respectively. Examination to GenBank annotations of the 55 PhcbHLH members indicated that 29 PhcbHLH proteins were annotated in consistence with our analytical result, 8 were annotated different with our analytical result, 12 were merely annotated as hypothetical protein, and the rest 6 were not deposited in GenBank. A comparison on insect bHLH gene composition revealed that human body louse possibly has more hairy and E(spl) genes than other insect species. Because hairy and E(spl) genes have been found to negatively regulate the differentiation of insect preneural cells, it is suggested that the existence of additional hairy and E(spl) genes in human body louse is probably the consequence of its long period adaptation to the relatively dark and stable environment. These data provide good references for further studies on regulatory functions of bHLH proteins in the growth and development of human body louse.

Clinical evaluation of pacemaker automatic capture management and atrioventricular interval extension algorithm.

AIMS: The present study was to assess the accuracy of automatic atrial and ventricular capture management (ACM and VCM) in determining pacing threshold and the performance of a second-generation automatic atrioventricular (AV) interval extension algorithm for reducing unnecessary ventricular pacing. METHODS AND RESULTS: A total of 398 patients at 32 centres who received an EnPulse dual-chamber pacing/dual-chamber adaptive rate pacing pacemaker (Medtronic, Minneapolis, MN, USA) were enrolled. The last amplitude thresholds as measured by ACM and VCM prior to the 6-month follow-up were compared with manually measured thresholds. Device diagnostics were used to evaluate ACM and VCM and the percentage of ventricular pacing with and without the AV extension algorithm. Modelling was performed to assess longevity gains relating to the use of automaticity features. Atrial and ventricular capture management performed accurately and reliably provided complete capture management in 97% of studied patients. The AV interval extension algorithm reduced the median per cent of right ventricular pacing in patients with sinus node dysfunction from 99.7 to 1.5% at 6-month follow-up and in patients with intermittent AV block (excluding persistent 3° AV block) from 99.9 to 50.2%. On the basis of validated modelling, estimated device longevity could potentially be extended by 1.9 years through the use of the capture management and AV interval extension features. CONCLUSION: Both ACM and VCM features reliably measured thresholds in nearly all patients; the AV extension algorithm significantly reduced ventricular pacing; and the use of pacemaker automaticity features potentially extends device longevity.

Prevalence of atrial fibrillation in China and its risk factors.

OBJECTIVE: To study the prevalence of atrial fibrillation (AF) and the relation with its risk factors in China. METHODS: A total of 19 363 participants (8635 males and 10 728 females) aged ⋝35 years in geographically dispersed urban and rural regions of China were included in this cross-sectional survey. All participants received questionnaire, physical and blood examination. Echocardiography were performed for AF patients found in the survey. RESULTS: Of the 19 363 participants, 199 were diagnosed with AF. The estimated age-standardized prevalence of AF was 0.78% in men and 0.76% in women. The prevalence of AF in participants aged <60 years was 0.41% in men and 0.43% in women, and was 1.83% in both men and women aged ⋝60 years. About 19.0% of males and 30.9% of females with AF were diagnosed with valve disease. Age- and sex-adjusted multivariable logistic regression analysis revealed that myocardial infarction, left ventricular hypertrophy (LVH), obesity, and alcohol consumption were associated with a increased risk of AF(P<0.05). CONCLUSION: The age standardized prevalence of AF is 0.77% in the participants enrolled in the present study. The number of AF cases aged ⋝35 years is 5.26 million according to 2010 Chinese Census. Most risk factors for AF, identified mainly in Western countries, are also detected in China.

Expression and functional validation of Bombyx mori nucleopolyhedrovirus ORF29, a conserved Nudix motif protein.

Our previous study showed that Bombyx mori nucleopolyhedrovirus (BmNPV) orf29 encodes a 26 kDa protein expressed in the early stage of infection cycle. BmNPV ORF29, contains a conserved motif of Nudix (nucleotide diphosphate X) superfamily. It has the highest homology with ADP-ribose pyrophosphatase (ADPRase), a subfamily of Nudix pyrophosphatase. In this work, we purified the recombinant BmNPV ORF29 in Escherichia coli by metal chelating affinity chromatography. The amino acid sequence of recombinant protein was confirmed by mass spectroscopic analysis and found that the purified protein could be able to catalyze the breakdown of ADP-ribose to AMP and ribose 5-phosphate, with Km and Kcat values of 182 µmol/l and 5.3 s-1 respectively. The optimal activity was at alkaline pH (8.5) with Mg2+ (0.5-mmol/l) ions as the cofactor.

[Retrospective analysis on the clinical features and management of acute and subacute right ventricular perforation by pacemaker lead].

OBJECTIVE: To describe the clinical characteristics and management of the acute and subacute cardiac perforation by pacing leads. METHODS: We retrospectively analyzed clinical data of patients with acute and subacute right ventricular perforation by pacemaker lead occurred in our hospital between 2006 and 2011. RESULTS: Seven cases of confirmed acute and subacute right ventricular perforation by pacemaker lead were enrolled. The perforation rate was 0.15%, 2 cases of perforation occurred during the procedure. The main manifestation was low blood pressure and pericardial effusion. These two patients with cardiac tamponade underwent urgent percutaneous pericardiocentesis and patients recovered without complication. The remaining 5 cases of perforation occurred within 4-16 days after the pacemaker implantation. The main symptoms were diaphragm stimulation and chest pain. Signs of leads dysfunction were observed in all 5 patients. The diagnosis of cardiac perforation was confirmed by chest X-ray, echocardiography, or computed tomography. In all these 5 patients, the leads were removed by simple traction under fluoroscopic guidance with surgical backup support, no complication was observed. CONCLUSION: Acute and subacute right ventricular perforation is a rare but serious complication of pacemaker implantation. In most patients, the leads can be safely removed under fluoroscopic guidance with surgical backup support and close monitoring.

Comparative proteome analysis of silkworm in its susceptibility and resistance responses to Bombyx mori densonucleosis virus.

Bombyx mori densonucleosis virus (BmDNV) is one of the most disastrous viruses in cocoon production. Silkworm resistance to BmDNV has been examined previously using a number of traditional biochemical and molecular techniques. In this study, a near isogenic line, BC(6), was constructed to eliminate the difference in inherited background, which has 99.9% identity with the susceptible strain but carries a resistant gene. We utilized a proteomic approach involving two-dimensional differential gel electrophoresis and mass spectrometry to examine changes in the midgut proteins from the susceptible and resistant silkworm larvae infected with BmDNV. The protein profiles were compared and 9 differentially expressed proteins were identified by mass spectrometry. In the resistant strains, the heat-shock 70-kDa protein cognate, cytochrome P450, vacuolar ATP synthase subunit B, arginine kinase, vacuolar ATP synthase subunit D and glutathione S-transferase sigma were strongly upregulated and α-tubulin was downregulated. Our results imply that these upregulated genes and the downregulated genes might be involved in B. mori immune responses against BmDNV-Z infection.

Cloning and expression analysis of an anti-lipopolysaccharide factor from giant freshwater prawn, Macrobrachium rosenbergii.

Anti-lipopolysaccharide factors (ALFs) are a group of effector molecules that are classified as antimicrobial peptides (AMPs). They are found in limulids and crustaceans and show a broad range of antimicrobial activity. In the current study, an ALF gene from Macrobrachium rosenbergii (MrALF) was identified. Its full length was 690 bp and it encoded a 124 amino acid protein. A signal peptide and a conserved LPS-binding domain with two conserved cysteine residues that comprise a cluster of positive charged residues within a disulfide loop were predicted in MrALF. The M. rosenbergii ALF clusters with the Macrobrachium olfersii ALF and further clusters with most crustacean ALFs, suggesting that they should originate from one common ancestor. Positive selections should have sharpen the evolution of M. rosenbergii and M. olfersii ALF genes. Reverse transcriptase polymerase chain reaction analysis showed that MrALF was expressed in all detected tissues. In the epidermis, MrALF was obviously upregulated 24 h after the LPS challenge. In the stomach and gills, MrALF was upregulated upon LPS challenge. The results show that MrALF might have important roles in the immune defense against invading bacteria. The positive selections that occur in the ALFs of crustaceans might have resulted from a Red Queen's race with its pathogens. We found evidence of positive selection acting to drive functional divergence during the evolution crustacean ALF genes, especially in the M. rosenbergii ALF gene. The evolutionary changes might correspond to the challenges induced by pathogens that infect crustaceans.

Heterogeneity of immune control in chronic hepatitis B virus infection: Clinical implications on immunity with interferon-α treatment and retreatment.

Hepatitis B virus (HBV) infection is a global public health issue. Interferon-α (IFN-α) treatment has been used to treat hepatitis B for over 20 years, but fewer than 5% of Asians receiving IFN-α treatment achieve functional cure. Thus, IFN-α retreatment has been introduced to enhance antiviral function. In recent years, immune-related studies have found that the complex interactions between immune cells and cytokines could modulate immune response networks, in-cluding both innate and adaptive immunity, triggering immune responses that control HBV replication. However, heterogeneity of the immune system to control HBV infection, particularly HBV-specific CD8+ T cell heterogeneity, has consequ-ential effects on T cell-based immunotherapy for treating HBV infection. Altogether, the host's genetic variants, negative-feedback regulators and HBV components affecting the immune system's ability to control HBV. In this study, we reviewed the literature on potential immune mechanisms affecting the immune control of HBV and the clinical effects of IFN-α treatment and retreatment.

Identification and Validation of Common Reference Genes for Normalization of Esophageal Squamous Cell Carcinoma Gene Expression Profiles.

Esophageal squamous cell carcinoma (ESCC) is one of the subtypes of esophageal cancer with Chinese characteristics, and its five-year survival rate is less than 20%. Early diagnosis is beneficial to improving the survival rate of ESCC significantly. Quantitative Real-Time Polymerase Chain Reaction is a high-throughput technique that can quantify tumor-related genes for early diagnosis. Its accuracy largely depends on the stability of the reference gene. There is no systematic scientific basis to demonstrate which reference gene expression is stable in ESCC and no consensus on the selection of internal reference. Therefore, this research used four software programs (The comparative delta-Ct method, GeNorm, NormFinder, and BestKeeper) to evaluate the expression stability of eight candidate reference genes commonly used in other tumor tissues and generated a comprehensive analysis by RefFinder. Randomly selected transcriptome sequencing analysis confirmed the SPP1 gene is closely related to ESCC. It was found that the expression trend of SPP1 obtained by RPS18 and PPIA as internal reference genes were the same as that of sequencing. The results show that RPS18 and PPIA are stable reference genes, and PPIA + RPS18 are a suitable reference gene combination. This is a reference gene report that combines transcriptome sequencing analysis and only focuses on ESCC, which makes the quantification more precise, systematic, and standardized, and promotes gene regulation research and the early diagnosis of ESCC in the future.

Metabolomics of Esophageal Squamous Cell Carcinoma Tissues: Potential Biomarkers for Diagnosis and Promising Targets for Therapy.

Background: The incidence of esophageal squamous cell carcinoma in China ranks first in the world. The early diagnosis technology is underdeveloped, and the prognosis is poor, which seriously threatens the quality of life of the Chinese people. Epidemiological findings are related to factors such as diet, living habits, and age. The specific mechanism is not clear yet. Metabolomics is a kind of omics that simultaneously and quantitatively analyzes the comprehensive profile of metabolites in living systems. It has unique advantages in the study of the diagnosis and pathogenesis of tumor-related diseases, especially in the search for biomarkers. Therefore, it is desirable to perform metabolic profiling analysis of cancer tissues through metabolomics to find potential biomarkers for the diagnosis and treatment of esophageal squamous cell carcinoma. Methods: HPLC-TOF-MS/MS technology and Illumina Hiseq Xten Sequencing was used for the analysis of 210 pairs of matched esophageal squamous cell carcinoma tissues and normal tissues in Zhenjiang City, Jiangsu Province, a high-incidence area of esophageal cancer in China. Bioinformatics analysis was also performed. Results: Through metabolomic and transcriptomic analysis, this study found that a total of 269 differential metabolites were obtained in esophageal squamous cell carcinoma and normal tissues, and 48 differential metabolic pathways were obtained through KEGG enrichment analysis. After further screening and identification, 12 metabolites with potential biomarkers to differentiate esophageal squamous cell carcinoma from normal tissues were obtained. Conclusions: From the metabolomic data, 4 unknown compounds were found to be abnormally expressed in esophageal squamous cell carcinoma for the first time, such as 9,10-epoxy-12,15-octadecadienoate; 3 metabolites were found in multiple abnormal expression in another tumor, but upregulation or downregulation was found for the first time in esophageal cancer, such as oleoyl glycine; at the same time, it was further confirmed that five metabolites were abnormally expressed in esophageal squamous cell carcinoma, which was similar to the results of other studies, such as PE.