The human gut microbiota regulates many host pathophysiological processes including metabolic, inflammatory, immune and cellular responses. In recent years, the incidence and mortality of lung cancer have increased rapidly, which is one of the biggest challenges in the field of cancer treatment today, especially in non-small cell lung cancer. Animal models and clinical studies have found that the gut microbiota of non-small cell lung cancer patients is significantly changed compared with the healthy people. The gut microbiota and metabolites can not only play a pro-cancer or tumor suppressor role by regulating immune, inflammatory responses and so on, but also be related with radiotherapy and chemotherapy of non-small cell lung cancer and the resistance of immunotherapy. Therefore, gut microbiota and related metabolites can be both potential markers for early diagnosis and prognosis in patients with non-small cell lung cancer and novel therapeutic targets for targeted drugs. This study will review the latest research progress of effect of gut microbiota on non-small cell lung cancer, and provide a new diagnosis and treatment ideas for non-small cell lung cancer.
ObjectiveTo investigate the expression of autophagy-related genes and proteins in the lung tissues of patients with non-small cell lung cancer (NSCLC).MethodsPulmonary tissues were obtained from the surgically resected lung tissues of patients with NSCLC who were clinical diagnosed. The lung cancer tissues were derived from the pathologically diagnosed NSCLC and the normal tissues were from lung tissues 5 cm away from the lung lesions (29 cases in the lung cancer group and 32 cases in the normal group). The expression of autophagy-related proteins ATG5, LC3B, and p62 in lung tissues were measured by Western blot, and mRNA expression of ATG5 and p62 in the lung tissues were measured by real-time PCR.ResultsWestern blot analysis showed that the expression of ATG5 and p62 in lung cancer group were significantly higher than those in normal group (P<0.05). However, the expression of LC3B in lung cancer group was significantly lower than that in normal group (P<0.05). Real-time PCR analysis found that the mRNA expression of ATG5 and p62 in lung cancer group were significantly higher than those in normal group (P<0.05). The expression of ATG5, LC3B and p62 had no relationship with gender, age, smoking history, tumor location, tumor size, clinicopathological classification, differentiation or TNM stage. The expression of ATG5 had statistical significance in lymph node metastasis (P<0.05), but there was no difference for LC3B or p62 in lymph node metastasis (P>0.05).ConclusionsAutophagy plays a role in the tumorigenesis of lung cancer. If it’s possible to regulate and control autophagy-related genes and proteins effectively, it may supply new insights or targets into treatment for lung cancer patients.
ObjectiveTo identify causal effects and potential mechanisms of oxidative stress (OS) genes in lung cancer. MethodsOS-related genes were extracted from the GeneCards database. Integration analysis of genome-wide association study (GWAS) data for lung cancer with gene expression and DNA methylation quantitative trait loci (eQTL and mQTL) in blood was performed using the summary data-based Mendelian randomization (SMR) approach to determine the causal relationship between OS genes and lung cancer risk. Colocalization analysis of OS gene QTLs and lung cancer risk loci was performed to gain insight into the potential regulatory mechanisms of lung cancer risk. ResultsA potential causal relationship between OS-related genes and lung cancer was identified by SMR analysis. AGER expression level was found to be associated with lung cancer risk [OR=1.944, 95%CI (1.431, 2.640), P<0.001], and ATF6B expression level was associated with lung cancer risk [OR=1.508, 95%CI (1.287, 1.767), P<0.001]. Meanwhile, ATF6B methylation level was associated with lung cancer risk. ConclusionOS-related genes are associated with lung cancer, which may be a potential site of action for anti-cancer drugs.
Objective To investigate the association between neuroticism and gastroesophageal reflux disease (GERD) using Mendelian randomization (MR). Methods Exposure and outcome data were downloaded from the IEU database (https://gwas.mrcieu.ac.uk/), containing summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and gastroesophageal reflux disease (n=602 604). Using the weighted median (WM), MR-Egger, inverse variance weighted (IVW), weighted mode and simple mode methods for Mendelian randomization analysis. Odds ratio (OR) values were used to assess the causal relationship, while sensitivity analysis was used to ensure the accuracy of the results. ResultsNeuroticism (OR=1.229, 95%CI 1.186-1.274, P<0.001) was associated with an increased risk of GERD. Meanwhile, gastroesophageal reflux disease (OR=1.786, 95%CI 1.623-1.965, P<0.001) was also associated with increased risk of neuroticism. Conclusion The study finds a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.
ObjectiveTo explore whether there is a causal relationship between intestinal flora and esophageal cancer. MethodsSummary statistics of intestinal flora and esophageal cancer were obtained from the genome-wide association studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. ResultsIn the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.001), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter[OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. ConclusionOxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.