BackgroundThe usefulness of ribonucleotide reductase catalytic subunit M1 (RRM1) for predicting the therapeutic effects of gemcitabine-containing chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. RRM1-positive patients show unique clinicopathological features.MethodsHere, we performed a meta-analysis to systematically evaluate the relationship between RRM1 expression and the clinicopathological characteristics of NSCLC patients treated with gemcitabine-containing regimens. A comprehensive electronic and manual search was performed to identify relevant articles. The pooled relative risk (RR) and 95% CI were used to estimate the relation between the clinicopathological characteristics of NSCLC patients and RRM1 expression.ResultsThe study included 31 observational studies and 3,667 patients. The analysis showed no significant association between RRM1 expression and pathological type, stage, and smoking status; however, RRM1 positivity was significantly lower in women than in men (43.0% vs 51.7%, RR=0.84, 95% CI: 0.74–0.94, P=0.004).ConclusionThe present pooled analyses demonstrated that RRM1 positivity in women with advanced NSCLC was associated with a higher rate of response to gemcitabine-containing regimens. Immunohistochemistry may be valuable to prescreen for RRM1 expression in clinical practice, whereas PCR can be routinely used as a verification method. These findings will help design suitable molecular-targeted therapies for NSCLC.
<b><i>Background:</i></b> This study detected the methylation levels of nuclear factor-5 <i>(NFAT5)</i>, <i>PVT1</i>, ribosomal protein S6 kinase A-1 (<i>RPS6KA1</i>), and <i>MIB1</i> in patients with steroid-resistant asthma (SRA) and explored their associations with SRA. <b><i>Methods:</i></b> In our pilot study, we found abnormal methylation of <i>NFAT5</i>, <i>PVT1</i>, <i>RPS6KA1,</i> and <i>MIB1</i> in SRA patients according to genome-wide methylation screening. This study expanded the sample size to further validate the results of the pilot study. Twenty patients with SRA, 20 patients with bronchial asthma, and 20 healthy volunteers constituted the SRA group, asthma control group, and healthy control group, respectively. The clinical data of all the participants were collected. Peripheral blood was taken for DNA extraction. The methylation loci and levels of <i>NFAT5</i>, <i>PVT1</i>, <i>RPS6KA1,</i> and <i>MIB1</i> were detected using the Sequenom MassARRAY Nanodispenser RS1000. Data were processed and analyzed with SPSS 22.0 software. <b><i>Results:</i></b> There were 24 CpG loci detected in the <i>NFAT5</i> segment 7 in the <i>PVT1</i> segment, 4 in the <i>RPS6KA1</i> segment, and 3 in the <i>MIB1</i> segment. Among these genes, RPS6KA exhibited hypomethylation in the SRA group, which showed significant differences at the CpG_1, CpG_2, and CpG_3 loci compared with the other groups (<i>p</i> < 0.05). No significant differences in the methylation levels of <i>NFAT5</i>, <i>PVT1</i>, and <i>MIB1</i> were observed among the groups (<i>p</i> > 0.05). <b><i>Conclusions:</i></b> <i>RPS6KA1</i> is hypomethylated in SRA patients, which may play a role in the development of SRA via the MAPK signaling pathway. However, the influence of the methylation of <i>NFAT5</i>, <i>PVT1,</i> and <i>MIB1</i> on SRA development remains to be explored.
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