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Isolated anti-HBc (IAHBc) is defined by the presence of anti-HBc in the absence of HBsAg and hepatitis B surface antibody (anti-HBs). IAHBc is of great clinical significance as a specific pattern of HBV infection, but IAHBc has not been fully clarified. This study aimed to explore the prevalence and influential factors of IAHBc from routine examination results of inpatients.A total of 61,247 individuals were included in the study, with a median age of 55 years (range: 43-68), and a male-to-female ratio of 0.90:1. The prevalence of current HBV infection (HBsAg positive) was 6.82%, while the prevalence of previous HBV infection (HBsAg negative but anti-HBc positive) was 48.63%. The prevalence of IAHBc was 12.31%. Among them, the rates for males were 7.10%, 52.16%, and 13.70%, respectively, which were significantly higher than the rates for females at 6.56%, 45.45%, and 11.06% (P < 0.05). The prevalence rates mentioned above were significantly reduced after vaccination (P < 0.05). The prevalence of IAHBc increases with age, rising from 0.23% in the age group of 15-29 years to 13.57% in individuals aged 80 and above. After the age of 50, the prevalence of IAHBc closely parallels the previous infection rate but shows no significant association with the current infection rate (P > 0.05). Among IAHBc individuals, approximately 33.83% tested positive for anti-HBe, and their anti-HBc absorbance values were significantly higher compared to anti-HBe negative individuals (7.08 and 5.31, P < 0.01). The prevalence of anti-HBe positivity among IAHBc individuals does not vary with changes in the previous infection rate and age (P > 0.05).
Subject(s)
Hepatitis B Antibodies , Hepatitis B , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , China/epidemiology , Hepatitis B/epidemiology , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens , PrevalenceABSTRACT
Background: Patients infected with SARS-CoV-2 Delta VOC have a longer course of disease. We detected the air, surfaces, and patient's personal items in the wards of the second hospital of Nanjing during the outbreak of the COVID-19 Delta Variant to identify the environmental contamination, which provides a theoretical basis for the prevention and control of COVID-19 variation beads in the future. Methods: In the cross-sectional study, we collected and analyzed clinical features, demographic and epidemiological data, laboratory and swab test results, and surface and air samples of 144 COVID-19 cases. Results: The time from symptom onset to surface sampling was 25 days (IQR, 21 to 33 days). Positive throat swabs were detected in 52(36.1%) patients, of which only 8(5.6%) patients had N or ORF1a/b genes Ct value <35 on the surface sampling day. Among the 692 environmental surface and air specimens collected from 144 COVID-19 cases, 3 specimens (3/692, 0.4%) related to 5 cases (3.5%, 5/144) were detected positive on RT-PCR. Overall, bedside tables (2/144, 1.4%) were most likely to be contaminated, followed by toilet seats (1/81, 1.2%). Conclusion: The environmental contamination by SARS-CoV-2 Delta VOC-infected cases with disease duration of more than two weeks is limited.
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What is already known about this topic?: Healthcare workers (HCWs) and previously infected patients (PIPs) may experience a wave of epidemic following the modification of the country's coronavirus disease (COVID)-zero policy in China. What is added by this report?: As of early January 2023, the initial wave of the COVID-19 pandemic among HCWs had effectively subsided, with no statistically significant differences observed in infection rates compared to those of their co-occupants. The proportion of reinfections among PIPs was relatively low, particularly in those with recent infections. What are the implications for public health practice?: Medical and health services have resumed normal operations. For patients who have recently experienced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, appropriate relaxation of policies may be considered.
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Objectives: C1s activation is associated with the pathogenesis of various diseases, indicating the potential value of C1s activation detection in clinic. Here we aimed to establish fluorescence resonance energy transfer (FRET)-based immunoassay for the quantitative detection of activated C1s in serum. Methods: FRET-based fluorogenic peptides, sensitive to the enzymatic activity of activated C1s, were prepared and labeled with the fluorophore ortho-aminobenzoic acid (Abz) and quencher 2,4-dinitrophenyl (Dnp), and then were further selected depending on its Kcat/Km value. C1s in the samples was captured and separated using anti-C1s-conjugated magnetic microbeads. Next, enzymatic activity of activated C1s in samples and standards was examined using fluorescent quenched substrate assays. Limit of detection (LOD), accuracy, precision, and specificity of FRET-based immunoassay were also investigated. Results: This method presented a linear quantification range for the enzymatic activity of activated C1s up to 10 µmol min-1 mL-1 and LOD of 0.096 µmol·min-1·mL-1 for serum samples. The recovery of the method was in the range of 90% ~ 110%. All CV values of the intra-analysis and inter-analysis of three levels in samples were less than 10%. The cross-reaction rates with C1r enzyme, MASP1, and MASP2 were less than 0.5%. No significant interferences were found with bilirubin (0.2 mg mL-1), Chyle (2000 FTU), and haemoglobin (5 mg mL-1), but anticoagulants (EDTA, citrate and heparin) inhibited the enzymatic ability of activated C1s. Thus, this established method can be used for the determination of active C1s in human serum samples in the concentration interval of 0.096-10.000 µmol min-1 mL-1. Conclusions: One anti-C1s-based FRET immunoassay for activated C1s detection in serum samples were established, and it will be useful to explore the role of C1s activation in the pathogenesis, diagnosis and treatment in complement-related diseases.
Subject(s)
Complement C1r , Complement C1s , Humans , Fluorescence Resonance Energy Transfer , Immunoassay , Peptides , Mannose-Binding Protein-Associated Serine ProteasesABSTRACT
Musashi 2 (MSI2) is an RNA-binding protein that regulates mRNA translation of numerous intracellular targets and plays an important role in the development of cancer. However, the prognostic value of MSI2 in various cancers remains controversial. Herein, we conducted this meta-analysis including 21 studies with 2640 patients searched from PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure databases, and WanFang databases to accurately assess the prognostic significance of MSI2 in various cancers. Our results indicated that high MSI2 expression was significantly related to poor overall survival (HR = 1.84, 95% CI: 1.66-2.05, P < 0.001) and disease-free survival (HR = 1.73, 95% CI: 1.35-2.22, P < 0.001). In addition, MSI2 positive expression was associated with certain phenotypes of tumor aggressiveness, such as clinical stage, depth of invasion, lymph node metastasis, liver metastasis and tumor size. In conclusion, elevated MSI2 expression is closely correlated with poor prognosis in various cancers, and may serve as a potential molecular target for cancer patients.
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BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Given its insidious onset, the condition often already progresses to advanced stage when symptoms occur. Thus, early diagnosis is of great significance for timely clinical intervention, efficacy enhancement, and prognostic improvement. Featuring high throughput, fastness, and rich information, next generation sequencing (NGS) can greatly shorten the detection time, which is a widely used detection technique at present. AIM: To screen specific genes or gene combinations in fecal DNA that are suitable for diagnosis and prognostic prediction of CRC, and to establish a technological platform for CRC screening, diagnosis, and efficacy monitoring through fecal DNA detection. METHODS: NGS was used to sequence the stool DNA of patients with CRC, which were then compared with the genetic testing results of the stool samples of normal controls and patients with benign intestinal disease, as well as the tumor tissues of CRC patients. Specific genes or gene combinations in fecal DNA suitable for diagnosis and prognostic prediction of CRC were screened, and their significances in diagnosing CRC and predicting patients' prognosis were comprehensively evaluated. RESULTS: High mutation frequencies of TP53, APC, and KRAS were detected in the stools and tumor tissues of CRC patients prior to surgery. Contrastively, no pathogenic mutations of the above three genes were noted in the postoperative stools, the normal controls, or the benign intestinal disease group. This indicates that tumor-specific DNA was detectable in the preoperative stools of CRC patients. The preoperative fecal expression of tumor-associated genes can reflect the gene mutations in tumor tissues to some extent. Compared to the postoperative stools and the stools in the two control groups, the pathogenic mutation frequencies of TP53 and KRAS were significantly higher for the preoperative stools (χ 2 = 7.328, P < 0.05; χ 2 = 4.219, P < 0.05), suggesting that fecal TP53 and KRAS genes can be used for CRC screening, diagnosis, and prognostic prediction. No significant difference in the pathogenic mutation frequency of the APC gene was found from the postoperative stools or the two control groups (χ 2 = 0.878, P > 0.05), so further analysis with larger sample size is required. Among CRC patients, the pathogenic mutation sites of TP53 occurred in 16 of 27 preoperative stools, with a true positive rate of 59.26%, while the pathogenic mutation sites of KRAS occurred in 10 stools, with a true positive rate of 37.04%. The sensitivity and negative predictive values of the combined genetic testing of TP53 and KRAS were 66.67% (18/27) and 68.97%, respectively, both of which were higher than those of TP53 or KRAS mutation detection alone, suggesting that the combined genetic testing can improve the CRC detection rate. The mutation sites TP53 exon 4 A84G and EGFR exon 20 I821T (mutation start and stop positions were both 7579436 for the former, while 55249164 for the latter) were found in the preoperative stools and tumor tissues. These "undetected" mutation sites may be new types of mutations occurring during the CRC carcinogenesis and progression, which needs to be confirmed through further research. Some mutations of "unknown clinical significance" were found in such genes as TP53, PTEN, KRAS, BRAF, AKT1, and PIK3CA, whose clinical values is worthy of further exploration. CONCLUSION: NGS-based fecal genetic testing can be used as a complementary technique for the CRC diagnosis. Fecal TP53 and KRAS can be used as specific genes for the screening, diagnosis, prognostic prediction, and recurrence monitoring of CRC. Moreover, the combined testing of TP53 and KRAS genes can improve the CRC detection rate.
Subject(s)
Colorectal Neoplasms , High-Throughput Nucleotide Sequencing , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA , High-Throughput Nucleotide Sequencing/methods , Humans , Mutation , Proto-Oncogene Proteins p21(ras)/geneticsABSTRACT
BACKGROUND: Cumulative evidence suggests that A-kinase interacting protein 1 (AKIP1) plays an important role in tumor progression. However, the prognostic value of AKIP1 expression in various cancers remains unclear. Here, we conducted a meta-analysis to evaluate the prognostic value of AKIP1 expression in patients with cancer. METHODS: The PubMed, Web of Science, EMBASE, CNKI, and Wanfang databases were systematically searched to identify studies in which the effect of AKIP1 expression on prognosis (overall survival or disease-free survival) was investigated. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the effect of AKIP1 expression on patient survival. Odds ratios (ORs) with 95% CIs were pooled to estimate the association between AKIP1 expression and clinicopathological characteristics of patients with cancer. RESULTS: Nineteen eligible studies, encompassing 3979 patients, were included in the meta-analysis. AKIP1 expression was negatively associated with overall survival (HRâ=â1.86, 95% CI: 1.58-2.18, Pâ<â.001) and disease-free survival (HRâ=â1.69, 95% CI: 1.53-1.87, Pâ<â.001) in patients with cancer. Moreover, AKIP1 overexpression was positively correlated with adverse clinicopathological features, such as tumor size (ORâ=â2.22, 95% CI: 1.67-2.94, Pâ<â.001), clinical stage (ORâ=â2.05, 95% CI: 1.45-2.90, Pâ<â.001), depth of tumor invasion (ORâ=â2.98, 95% CI: 2.21-4.02, Pâ<â.001), and degree of lymph node metastasis (ORâ=â2.12, 95% CI: 1.75-2.57, Pâ<â.001). CONCLUSIONS: High AKIP1 expression is an unfavorable prognostic biomarker and may serve as a potential therapeutic target in patients with cancer.
Subject(s)
Biomarkers, Tumor , Nuclear Proteins , Adaptor Proteins, Signal Transducing/metabolism , Biomarkers, Tumor/metabolism , China , Disease-Free Survival , Humans , Lymphatic Metastasis , Nuclear Proteins/metabolism , PrognosisABSTRACT
METHODS: PubMed, Web of Science, Embase, CNKI, and Wanfang databases were thoroughly searched for eligible studies, in which the relationship between SPHK1 expression and cancer prognosis was evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to estimate the impact of SPHK1 expression on cancer patients' survival. Odds ratios (ORs) and 95% CIs were combined to assess the association between SPHK1 expression and clinicopathological characteristics of cancer patients. The certainty of evidence was evaluated by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Thirty studies comprising 32 cohorts with 5965 patients were included in this meta-analysis. The outcomes indicated that elevated SPHK1 expression was associated with worse overall survival (OS) (HR = 1.71, 95% CI: 1.45-2.01, P < 0.001) and disease-free survival (DFS) (HR = 1.34, 95% CI: 1.13-1.59, P = 0.001). What is more, SPHK1 overexpression was significantly correlated with certain phenotypes of tumor aggressiveness, such as clinical stage (OR = 2.07, 95% CI: 1.39-3.09, P < 0.001), tumor invasion (OR = 2.16, 95% CI: 1.47-3.18, P < 0.001), lymph node metastasis (OR = 2.04, 95% CI: 1.71-2.44, P < 0.001), and distant metastasis (OR = 3.16, 95% CI: 2.44-4.09, P < 0.001). The quality of the evidence for both OS and DFS was low. CONCLUSIONS: Increased SPHK1 expression is related to poor prognosis in human cancers and may serve as a promising prognostic marker and therapeutic target for malignant patients. However, conclusions need to be treated with caution because of lack of high quality of evidence.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Biomarkers, Tumor/metabolism , Neoplasms/diagnosis , Neoplasms/metabolism , Neoplasms/mortality , Humans , PrognosisABSTRACT
Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has induced a worldwide pandemic since early 2020. COVID-19 causes pulmonary inflammation, secondary pulmonary fibrosis (PF); however, there are still no effective treatments for PF. The present study aimed to explore the inhibitory effect of dihydroartemisinin (DHA) on pulmonary inflammation and PF, and its molecular mechanism. Morphological changes and collagen deposition were analyzed using hematoxylin-eosin staining, Masson staining, and the hydroxyproline content. DHA attenuated early alveolar inflammation and later PF in a bleomycin-induced rat PF model, and inhibited the expression of interleukin (IL)-1ß, IL-6, tumor necrosis factor α (TNFα), and chemokine (C-C Motif) Ligand 3 (CCL3) in model rat serum. Further molecular analysis revealed that both pulmonary inflammation and PF were associated with increased transforming growth factor-ß1 (TGF-ß1), Janus activated kinase 2 (JAK2), and signal transducer and activator 3(STAT3) expression in the lung tissues of model rats. DHA reduced the inflammatory response and PF in the lungs by suppressing TGF-ß1, JAK2, phosphorylated (p)-JAK2, STAT3, and p-STAT3. Thus, DHA exerts therapeutic effects against bleomycin-induced pulmonary inflammation and PF by inhibiting JAK2-STAT3 activation. DHA inhibits alveolar inflammation, and attenuates lung injury and fibrosis, possibly representing a therapeutic candidate to treat PF associated with COVID-19.
Subject(s)
Artemisinins/therapeutic use , Pneumonia/prevention & control , Pulmonary Fibrosis/prevention & control , Animals , Artemisinins/pharmacology , Janus Kinase 2/antagonists & inhibitors , Male , Rats , Rats, Wistar , STAT3 Transcription Factor/antagonists & inhibitors , Signal Transduction/drug effectsABSTRACT
BACKGROUND: Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2), a newly discovered member of the B7 family, is overexpressed in numerous tumors. However, the prognostic impact of HHLA2 in human cancers remains controversial. Thus, we performed this meta-analysis to explore the prognostic value of HHLA2 in Chinese patients with solid tumors. METHODS: PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and WanFang databases were systematically searched for eligible studies that evaluated the impact of HHLA2 on overall survival (OS) in patients with cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the association between HHLA2 expression and OS in solid tumors. Odds ratios (ORs) and 95% CIs were pooled to assess the correlation between HHLA2 expression and clinicopathological characteristics in solid tumors. RESULTS: A total of 12 studies, including 15 cohorts and 1747 patients, were included in this meta-analysis. We found that high HHLA2 expression was significantly associated with shorter OS (HRâ=â1.65, 95% CI: 1.12-2.43). Subgroup analysis by cancer type demonstrated that high HHLA2 expression was associated with poor OS in patients with clear cell renal cell carcinoma (HRâ=â3.42, 95% CI: 2.39-4.91), gastric cancer (HRâ=â2.03, 95% CI: 1.31-3.16), intrahepatic cholangiocarcinoma (HRâ=â1.77, 95% CI: 1.24-2.53), lung cancer (HRâ=â2.14, 95% CI: 1.33-3.44) and other cancer types (HRâ=â2.08, 95% CI: 1.34-3.24), but not in patients with epithelial ovarian cancer (HRâ=â0.52, 95% CI: 0.08-3.56). Nevertheless, high HHLA2 expression was associated with better OS in patients with pancreatic ductal adenocarcinoma (HRâ=â0.45, 95% CI: 0.32-0.64). Furthermore, high HHLA2 expression was associated with old age (ORâ=â1.30, 95% CI: 1.03-1.63), lymph node metastasis (ORâ=â1.99, 95% CI: 1.41-2.81), and vascular invasion (ORâ=â1.69, 95% CI: 1.18-2.42). CONCLUSIONS: HHLA2 may serve as a potential prognostic biomarker for solid tumors in Chinese population, by predict the prognosis of cancer patients based on their tumor types.
Subject(s)
Immunoglobulins/metabolism , Neoplasms/metabolism , Humans , Neoplasms/diagnosis , Neoplasms/mortality , PrognosisABSTRACT
METHODS: We comprehensively searched electronic databases, namely, PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases up to December 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the association between PRDX1 protein expression and the survival of patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to estimate the correlation between PRDX1 protein expression and clinicopathologic characteristics in the patients. RESULTS: Seventeen cohort studies that involved 2,858 patients were included in this meta-analysis. The pooled results indicated that positive PRDX1 expression was related to poor overall survival (HR = 1.68, 95% CI: 1.24-2.27, P = 0.001) and disease-free survival (HR = 1.88, 95% CI: 1.31-2.70, P = 0.001). In addition, high PRDX1 expression was associated with large tumor size (OR = 1.69, 95% CI: 1.07-2.68, P = 0.025), advanced TNM stage (OR = 2.26, 95% CI: 1.24-4.13, P = 0.008), and poor tumor differentiation (OR = 0.59, 95% CI: 0.44-0.81, P = 0.001). CONCLUSIONS: PRDX1 overexpression is associated with poor outcomes of cancers and may serve as a prognostic biomarker for malignant patients. Hence, PRDX1 could be a new target for antitumor therapy.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma/genetics , Peroxiredoxins/genetics , Adult , Aged , Biomarkers, Tumor/metabolism , Carcinoma/metabolism , Carcinoma/pathology , Cohort Studies , Female , Humans , Male , Middle Aged , Peroxiredoxins/metabolism , Survival Analysis , Tumor BurdenABSTRACT
BACKGROUND: As a member of the N-myc down-regulated gene family, N-Myc downstream-regulated gene 2 (NDRG2) contributes to the tumorigenesis of various types of cancers. However, the correlation between NDRG2 expression and the prognosis of solid tumor remains to be elucidated because of small sample sizes and inconsistent results in previous studies. In the present study, we conducted a systematic review and meta-analysis to explore the prognostic significance of NDRG2 in human solid tumors. METHODS: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, and WanFang databases (up to April 2020) were searched for relevant studies that evaluated the impact of NDRG2 on clinical outcomes, including overall survival (OS), and disease-free survival (DFS), in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to assess the association between NDRG2 expression and the survival of patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to estimate the correlation between NDRG2 expression and clinicopathologic characteristics in the patients. RESULTS: A total of 13 eligible studies with 1980 patients were included in this meta-analysis. Low NDRG2 expression was significantly associated with poor OS (HRâ=â1.96, 95% CI: 1.60-2.40, Pâ<â.001) and DFS (HRâ=â2.70, 95% CI: 1.42-5.13, Pâ=â.002) in solid tumor. Furthermore, low NDRG2 expression was related to some phenotypes of tumor aggressiveness, such as clinical stage (ORâ=â3.21, 95% CI: 1.96-5.26, Pâ<â.001), lymph node metastasis (ORâ=â2.14, 95% CI: 1.49-3.07, Pâ<â.001), and degree of differentiation (ORâ=â0.60, 95% CI: 0.45-0.81, Pâ=â.001). CONCLUSIONS: NDRG2 may be a meaningful biomarker of poor prognosis and a potential therapeutic target for human solid tumors.
Subject(s)
Neoplasms/metabolism , Tumor Suppressor Proteins/metabolism , Cohort Studies , Humans , Neoplasms/diagnosis , PrognosisABSTRACT
BACKGROUND AND OBJECTIVE: The L-type amino acid transporter 1 (LAT1, SLC7A5) is overexpressed in various types of cancer and has been thought to assist cancer progression through its uptake of neutral amino acids. However, the prognostic role of LAT1 in human cancers remains uncharacterized. Therefore, we conducted this meta-analysis to determine the prognostic significance of LAT1 in various cancers. METHODS: We systematically searched the PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and WanFang databases to collect relevant cohort studies investigating the prognostic value of LAT1 expression in patients with cancer. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to clarify the association between the LAT1 expression and the survival of patients with cancer. Odds ratios (ORs) with 95% CIs were calculated to appraise the correlation between LAT1 and the clinicopathological characteristics in patients with cancer. RESULTS: A total of 32 eligible articles, including 34 cohorts and 6410 patients, were enrolled in this meta-analysis. Our results demonstrated that high LAT1 expression was significantly associated with poor overall survival (HR = 1.66, 95% CI 1.41-1.96, P < 0.001), cancer-specific survival (HR = 1.64, 95% CI 1.31-2.05, P < 0.001), disease-free survival (HR = 1.55, 95% CI 1.31-1.83, P < 0.001), and progression-free survival (HR = 1.18, 95% CI 1.02-1.37, P = 0.026) in patients with cancer. In addition, we found that the elevated expression level of LAT1 was significantly related to certain phenotypes of tumor aggressiveness, such as tumor size, clinical stage, T stage, lymphatic invasion, vascular invasion, tumor differentiation, Ki-67, CD34, CD98, p53, and system ASC amino acid transporter-2. CONCLUSIONS: Elevated expression of LAT1 is associated with poor prognosis in human cancers and may serve as a potential prognostic marker and therapeutic target for patients with malignancies.
Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Large Neutral Amino Acid-Transporter 1/genetics , Neoplasms/genetics , Neoplasms/mortality , Humans , Large Neutral Amino Acid-Transporter 1/metabolism , Neoplasm Grading , Neoplasm Staging , Neoplasms/diagnosis , Odds Ratio , Organ Specificity , Prognosis , Proportional Hazards Models , Publication BiasABSTRACT
Colorectal cancer (CRC) is one of the most common types of cancer in the world, and targeted therapy is frequently used in the clinical management of the disease. A complete and accurate picture of tissue gene mutations is therefore critical. Tissue specimens from 117 patients with CRC were used for high throughput DNA next-generation sequencing (NGS) analysis. Hotspots from 50 genes frequently associated with the development and progression of solid tumors were targeted for sequencing. Characterization of tissue gene mutations was performed; the tissue mutation positive rates of KRAS, KIT, PIK3CA, MET and EGFR were 52.1, 19.7, 29.9, 15.4 and 14.5%, respectively. The mutation positive rates of TP53, APC, CDKN2A, STK11 and FBXW7 were 65.8, 39.3, 32.5, 19.7 and 19.7%, respectively. The most frequent KRAS mutations were G12A/C/D/S/V, accounting for 61.2% of all KRAS mutations. The most frequent TP53 mutations were R273C/G/H/L, accounting for 8.5% of all TP53 mutations. The most frequent APC mutation was E1554fs, accounting for 19.7% of all APC mutations. IDH1 R132C/H, KIT M541L, MET N375S, and SMAD4 R361C/H were also frequently identified. TP53 mutations were more common in patients ≥60 years old (P<0.05), and IDH1 mutations were more common in male patients (P<0.05). NGS 50 gene panel sequencing provides a comprehensive tissue gene mutation profile which may significantly improve clinical management.
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BACKGROUND AND AIM: Aspartate aminotransferase-to-platelet ratio index (APRI) is widely used in the assessment of fibrosis and cirrhosis, especially in patients with chronic hepatitis. However, the prognostic value of APRI in patients with chronic hepatitis with regard to the prediction of hepatocellular carcinoma (HCC) occurrence remains controversial. The objective of this meta-analysis is to investigate the association between APRI and HCC risk on the basis of cohort studies. METHODS: We systematically reviewed PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure databases for relevant cohort studies up to May 1, 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and subgroup analyses were calculated with Stata 12.0 software for the assessment of the relationship between APRI and HCC risk. RESULTS: A total of 13 studies, involving 8897 patients, were included in the meta-analysis, of which 11 explored the association between pretreatment APRI and HCC risk and four reported the relationship between posttreatment APRI and HCC risk. Pooled results showed that an elevated level of pretreatment APRI was associated with increased HCC risk (HR = 2.56, 95% CI: 1.78-3.68). When stratified by hepatitis type, high pretreatment APRI predicted HCC development in patients with chronic hepatitis B (CHB) and C (CHC) but not in alcoholic liver cirrhosis (ALC). In the subgroup analyses of study region, cut-off value, sample size, and analysis method, the relationship between high pretreatment APRI and increased HCC risk was significant. Meanwhile, patients with a high level of posttreatment APRI suffered from high HCC risk (HR = 3.69, 95% CI: 2.52-5.42). Conclusion: Results revealed a significant association between elevated APRI and HCC development in patients with chronic hepatitis, suggesting that APRI might serve as a valuable predictor for HCC risk in patients with chronic hepatitis.
Subject(s)
Aspartate Aminotransferases/metabolism , Blood Platelets/pathology , Carcinoma, Hepatocellular/pathology , Hepatitis B, Chronic/complications , Hepatitis C, Chronic/complications , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/etiology , Cohort Studies , Hepacivirus/isolation & purification , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/virology , Hepatitis C, Chronic/virology , Humans , Liver Neoplasms/enzymology , Liver Neoplasms/etiology , PrognosisABSTRACT
BACKGROUND/AIMS: Serum apolipoprotein A1 (apoA1) has been reported to be abnormally expressed in several malignancies. However, the prognostic role of apoA1 in solid tumors is still controversial. We conducted this meta-analysis to obtain a more accurate evaluation of prognostic significance of apoA1 in Chinese patients with solid tumors. METHODS: A comprehensive literature search of electronic databases was carried out up to August 2018. We included studies investigating the association between pretreatment serum apoA1 level and clinicopathological features, including survival outcomes, in solid tumors. Hazard ratios (HRs) and odds ratio (ORs) with 95% confidence intervals (CIs) were applied as effect size estimates. RESULTS: A total of 13 studies and 8052 patients were included in our meta-analysis. Elevated level of pretreatment serum apoA1 was markedly associated with an improved OS (pooled HR = 0.608, 95% CI = 0.557 - 0.665, P < 0.001). The statistical significances were observed in all cancer types, including digestive system malignancies (pooled HR = 0.633; 95% CI = 0.550-0.727; P < 0.001), urinary system cancers (pooled HR = 0.471; 95% CI = 0.352-0.630; P < 0.001), nasopharyngeal cancer (pooled HR = 0.642; 95% CI = 0.538-0.766; P < 0.001) and non-small cell lung cancer (pooled HR = 0.526; 95% CI = 0.329-0.841; P = 0.007), but not in breast cancer (pooled HR = 0.573; 95% CI = 0.266-1.246; P = 0.155). Meanwhile, cancer patients with a low level of serum apoA1 suffered an unfavorable DFS (pooled HR = 0.714, 95% CI = 0.603 - 0.845, P < 0.001). Moreover, abnormal serum apoA1 was significantly correlated to tumor size (pooled OR = 0.640, 95% CI = 0.475 - 0.863, P = 0.003), tumor differentiation (pooled HR = 0.724, 95% CI = 0.565 - 0.929, P = 0.011), and tumor stage (pooled HR = 0.493, 95% CI = 0.384 - 0.633, P < 0.001). CONCLUSION: Elevated level of pretreatment serum apoA1 was significantly associated with longer survival in patients with solid tumors. Pretreatment serum apoA1 could serve as a novel positive factor for malignant patient prognosis in Chinese population.