Pan-cancer analysis of forkhead box Q1 as a potential prognostic and immunological biomarker.

Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family involved in the occurrence and development of different tumors. However, the specific expression patterns and functions of FOXQ1 in pan-cancer remain unclear. Therefore, we collected the expression, mutation, and clinical information data of 33 tumors from The Cancer Genome Atlas database. Via public pan-cancer transcriptome data analysis, we found that FOXQ1 is differentially expressed in various tumors at tissue and cell levels, such as liver hepatocellular carcinoma, colon adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, thyroid carcinoma, and kidney renal clear cell carcinoma. Kaplan-Meier and Cox analyses suggested that FOXQ1 expression was associated with poor overall survival of cutaneous melanoma and thymoma. Its expression was also associated with good disease-specific survival (DSS) in prostate adenocarcinoma but poor DSS in liver hepatocellular carcinoma. In addition, FOXQ1 expression was associated with poor disease-free survival of pancreatic adenocarcinoma. Moreover, FOXQ1 expression was closely related to the tumor mutational burden in 14 tumor types and microsatellite instability (MSI) in 8 tumor types. With an increase in stromal and immune cells, FOXQ1 expression was increased in breast invasive carcinoma, pancreatic adenocarcinoma, thyroid carcinoma, lung adenocarcinoma, and ovarian serous cystadenocarcinoma, while its expression was decreased in pancreatic adenocarcinoma, bladder urothelial carcinoma, and stomach adenocarcinoma. We also found that FOXQ1 expression was related to the infiltration of 22 immune cell types in different tumors (p < 0.05), such as resting mast cells and resting memory CD4 T cells. Last, FOXQ1 was coexpressed with 47 immune-related genes in pan-cancer (p < 0.05). In conclusion, FOXQ1 expression is closely related to prognosis, clinicopathological parameters, cancer-related pathway activity, the tumor mutational burden, MSI, the tumor microenvironment, immune cell infiltration, and immune-related genes and has the potential to be a diagnostic and prognostic biomarker as well as an immunotherapy target for tumors. Our findings provide important clues for further mechanistic research into FOXQ1.

Identification of Key Biomarkers in Systemic Lupus Erythematosus by a Multi-Cohort Analysis.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple body systems with heterogeneous clinical manifestations. Since gene expression analyses have been accomplished on diverse types of samples to specify SLE-related genes, single-cohort transcriptomics have not produced reliable results. Using an integrated multi-cohort analysis framework, we analyzed whole blood cells from SLE patients from three transcriptomics cohorts (n=1222) and identified a five-gene signature that distinguished SLE patients from controls. We validated the diagnostic performance of this five-gene signature in six independent validation cohorts (n= 469), with an area under the receiver operating characteristic curve of 0.88 [95% CI 0.7 - 0.96]. This five-gene signature may be associated with the proportion of SLE immune cells, and generalizable across ages and sample types with real diagnostic value for clinical application.

Association between p53 Arg72Pro polymorphism and colorectal cancer risk in Asian population: a meta-analysis.

Although several published studies have investigated the association between p53 Arg72Pro polymorphism and the risk of colorectal cancer (CRC), their results have been ambiguous. To examine the overall relationship between published case-control studies of Asian subjects, we conducted a meta-analysis based on 13 studies. Databases PubMed, EMBASE, Web of Knowledge, and the Chinese National Knowledge Infrastructure were screened for studies carried out up to November 1, 2017. To evaluating the association, crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated. The results of our meta-analysis indicated that the p53 Arg72Pro gene polymorphism does not correlate with the risk of CRC in the pooled analysis. However, significant results were found in Chinese population (allele model: OR = 1.26, 95% CI = 1.03-1.53; homozygous model: OR = 1.62, 95% CI = 1.09-2.40; recessive model: OR = 1.49, 95% CI = 1.22-1.82). Moreover, in subgroup analyses, the Pro/Pro genotype was significantly associated with rectal cancer, and not colon cancer. Stratification by source of control and gender indicated that Pro/Pro genotype and Pro allele also correlated with CRC risk in the population-based subgroup and in men. Thus, our current meta-analysis indicates no evidence for the association between the p53 Arg72Pro polymorphism and CRC risk in the Asian population, but significant association in Chinese population, especially for rectal cancer and in men. Further research with larger population sizes is still warranted to confirm this result.

Expression of serum let-7c, let-7i, and let-7f microRNA with its target gene, pepsinogen C, in gastric cancer and precancerous disease.

This study examined the expression patterns of serum let-7 microRNA (miRNA) and its target gene, pepsinogen C (PGC), in gastric cancer (GC) and precancerous disease patients to evaluate their diagnostic efficiency for GC and its precursor and to investigate any correlation between the two. Serum samples were taken from 638 patients, including 214 GC patients, 222 atrophic gastritis (AG) patients, and 202 controls (CON). The expression of serum let-7 miRNA was detected in control-AG (precancerous disease) through to GC patients using quantitative reverse-transcription polymerase chain reaction. Serum PGC was determined by enzyme-linked immuno-sorbent assay. PGC expression in situ was detected by immunohistochemistry staining. The luciferase reporter gene system was used to verify correlation between let-7 miRNA and its predicted target gene. The results showed that serum let-7c, let-7i, and let-7f demonstrated significant differences in the CON-AG-GC sequence (P = 0.017, P < 0.001, P = 0.003, respectively); let-7c was significantly lower in the AG group, and let-7i and let-7f were significantly higher in the GC group. Significantly different expressions of serum PGC were found among the three diseases, and also between AG vs. CON, and GC vs. CON (P = 0.027, P = 0.001, respectively). Linear-regression analysis suggested that serum let-7c was negatively correlated to the expression of PGC (r = -0.096, P = 0.047), and serum let-7c, let-7i, and let-7f showed no association with PGC expression in tissue. In addition, serum let-7c, let-7f, and let-7i showed significant correlations with environment factors. Serum let-7c, let-7i, and let-7f demonstrated significant differences in the CON-AG-GC disease sequence indicating that let-7 miRNA might have value by serving as potential biomarker in the diagnosis of GC or its precancerous diseases. There were significant negative correlations between serum let-7c and its target gene PGC expression.

A new polymorphism biomarker rs629367 associated with increased risk and poor survival of gastric cancer in chinese by up-regulated miRNA-let-7a expression.

BACKGROUND: Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. METHODS: A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing. RESULTS: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001). CONCLUSIONS: pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer.

Expression of serum miR-20a-5p, let-7a, and miR-320a and their correlations with pepsinogen in atrophic gastritis and gastric cancer: a case-control study.

BACKGROUND: The identification of serial miRNAs targeting the same functional gastric protein could provide new and effective serological biomarkers for the diagnosis of gastric cancer (GC). The aim of this study was to evaluate the potential of miR-20a-5p, let-7a and miR-320a in the diagnosis of AG or GC and the correlation of the three miRNAs with their predicted target molecules PGA, PGC and PGA/PGC ratio. METHODS: The total of 291 patients included 103 controls (CON), 94 with atrophic gastritis (AG) and 94 with GC. The levels of serum miRNAs were detected by quantitative reverse transcription-polymerase chain reaction and serum pepsinogen A (PGA) and C (PGC) were determined by enzyme-linked immunosorbent assays. RESULTS: Serum miR-320a level decreased through the controls, AG and GC groups which were the cascades of GC development, while there were no significant differences in levels of miR-20a-5p and let-7a among the controls, AG and GC groups. When stratified by gender and age, serum miR-320a expression was lower in female GC patients than in controls (p = 0.035), especially in female GC patients older than 60 years (p = 0.008). For distinguishing female GC patients aged over 60, the area under the receiver operating characteristic curve for miR-320a was 0.699, and the best cut-off point was 4.76 with a sensitivity of 65.2% and specificity of 68.2%. Concerning the correlations between the selected miR-20a-5p, let-7a, miR-320a and PGs, we found that there were positive correlations between all the three and the ratio of PGA/PGC (r = 0.408, 0.255, 0.324; p = <0.001, 0.009, 0.001, respectively), but there was no relationship between the expression of serum miR-20a-5p and its predicted target PGA, or between let-7a and miR-320a and their predicted target PGC. Serum miR-320a was decreased and PGC was increased in the GC group compared with the control group. CONCLUSIONS: Levels of serum miR-320a were lower in female GC patients older than 60 than in controls, which may provide a potential valuable marker for diagnosing older women with GC. The levels of serum miR-20a-5p, let-7a and miR-320a were positively correlated with PGA/PGC, which may indirectly reflect the functional status of the gastric mucosa.