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Background: Inflammation is not only involved in the development and progression of cancer but also affects the response to therapy. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in inflammation genes with the prognosis of advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Methods: Forty-seven SNPs were genotyped in 318 advanced NSCLC patients receiving EGFR-TKIs. Of 318 patients, 182 (57.2%) patients died during follow-up period. We assessed the association of SNPs with the progression-free survival (PFS) and overall survival (OS) as well as calculated the weighted genetic risk score (GRS). We also explored the expression levels and prognostic values of inflammation genes in lung adenocarcinoma (LUAD) in Gene Expression Profiling Interactive Analysis (GEPIA) and using UCSC Xena, respectively. The relationship between the expression levels of IL15, IL17RA, AGER, MIF, and TNFRSF1A and EGFR mutation status was analyzed using UCSC Xena. Results: In single variant analyses, 3 SNPs (rs10519613, rs4819554, and rs4149570) were significantly associated with worse PFS. Five SNPs (rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) were significantly with worse OS. In addition, high and intermediate GRSs (based on rs10519613, rs4819554, and rs4149570) were associated with worse PFS than those with low GRS. For OS, patients with high GRSs (based on rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) had shorter survival time than those with low GRS. Furthermore, IL15, IL17RA, AGER, MIF, and TNFRSF1A were dysregulated in LUAD. There was difference in the expression level of TNFRSF1A between EGFR wildtype and EGFR-mutant LUAD. Both low AGER expression and high TNFRSF1A expression were significantly associated with worse PFS in LUAD. In addition, low IL17RA and AGER expression, high MIF and TNFRSF1A expression were significantly associated with worse OS in LUAD. Conclusion: SNPs in inflammation genes could serve as prognostic biomarkers for NSCLC patients treated with EGFR-TKIs.
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BACKGROUND: The burden of pulmonary tuberculosis (TB) and diabetes mellitus (DM) have become serious global concerns, while the comprehensive evaluations of DM status and drug resistance in TB patients are still lacking. METHODS: All details of TB cases were collected from drug resistance monitoring sentinels in Zhejiang province. Fisher's exact test or Pearson chi-square test (χ2) was used to compare the baseline characteristics among TB with different DM statuses. The logistic regression model was used to estimate the relationship between DM and different drug resistance spectra. Univariate analysis and multivariate logistic model were used to explore the possible risk factors of drug resistance in TB patients with DM and no DM. RESULTS: 936 TB cases with smear-positive in Zhejiang province were collected, in which 76 patients (8.12%) owned the co-morbidity of DM. TB-DM prevalence was higher in older, Han nationality, employed, accompanied by no health insurance and hepatitis B status. Among 860 cases of TB-no DM and 76 cases of TB-DM, drug resistance-TB accounted for 31.51% and 23.68% (P > 0.05), MR-TB accounted for 15.93% and 14.47% (P > 0.05), respectively. MDR-TB was 4.88% and 6.58% (P > 0.05). The incidence of poly-drug resistant tuberculosis (PDR-TB) in TB-no DM patients (10.70 vs. 2.63%, OR: 4.43; 95% CI, 1.07-18.36) was higher than that in the TB-DM group (P < 0.05). In univariate and multivariate analysis, none of the basic factors were statistically significant with drug resistance among TB-DM cases (all P > 0.05). Retreatment was the risk factor of drug resistance among TB-no DM cases. CONCLUSIONS: Our results showed that the drug resistance rate of the TB-DM group was not higher than that of the TB-no DM group. Patients with TB-no DM were at a higher risk for PDR-TB, but not for MDR-TB, MR-TB, and drug resistance-TB. Special attention should be paid to TB-no DM patients who have been previously treated. In the future, large-scale and well-designed prospective studies are needed to clarify the impact of DM on the drug-resistance among TB.