scholarly journals Lung microbiome alterations in NSCLC patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leliang Zheng ◽  
Ruizheng Sun ◽  
Yinghong Zhu ◽  
Zheng Li ◽  
Xiaoling She ◽  
...  

AbstractLung is colonized by a diverse array of microbes and the lung microbiota is profoundly involved in the development of respiratory diseases. There is little knowledge about the role of lung microbiota dysbiosis in lung cancer. In this study, we performed metagenomic sequencing on bronchoalveolar lavage (BAL) from two different sampling methods in non-small cell lung cancer (NSCLC) patients and non-cancer controls. We found the obvious variation between bronchoscopy samples and lobectomy samples. Oral taxa can be found in both bronchoscopy and lobectomy samples and higher abundance of oral taxa can be found in bronchoscopy samples. Although the NSCLC patients had similar microbial communities with non-cancer controls, rare species such as Lactobacillus rossiae, Bacteroides pyogenes, Paenibacillus odorifer, Pseudomonas entomophila, Magnetospirillum gryphiswaldense, fungus Chaetomium globosum et al. showed obvious difference between NSCLC patients and non-cancer controls. Age-, gender-, and smoking-specific species and EGFR expression-related species in NSCLC patients were detected. There results implicated that different lung segments have differential lung microbiome composition. The oral taxa are found in the lobectomy samples suggesting that oral microbiota are the true members of lung microbiota, rather than contamination during bronchoscopy. Lung cancer does not obviously alter the global microbial composition, while rare species are altered more than common species. Certain microbes may be associated with lung cancer progression.

2018 ◽  
Vol 5 (3) ◽  
pp. 550
Author(s):  
Shivalingaswamy Salimath ◽  
Jayaraj B. S. ◽  
Mahesh P. A. ◽  
M. D. Majeed Pasha ◽  
Lokesh K. S. ◽  
...  

Background: Epidermal Growth Factor Receptor (EGFR) is one of the important molecules involved in lung cancer initiation and progression. Studies on over expression of EGFR and its survival in relation with Non-small cell lung cancer (NSCLC) patients have yielded controversial results. Prevalence of EGFR expression in NSCLC patients and 6-month survival in south Indian population is unknown.Methods: We carried out a prospective study in tertiary hospital. Diagnosed patients with NSCLC were included in the study and were interviewed with questionnaire containing demography and investigations like Chest X-ray, CT thorax, Bronchoscopy were recorded. EGFR expression analysis was done for all patients and were followed up monthly for 6 months and details of survival and treatment were collected. Cox regression analysis was used to assess their survival.Results: 50 patients with NSCLC were included. Forty-four (88%) were men, median age of study group was 65 years. Twenty-seven patients (54%) had Adenocarcinoma, 14 patients (28%) had Squamous cell carcinoma, 7 patients (14%) had poorly differentiated carcinoma and 2 patients (4%) had large cell carcinoma. Thirty-four (68%) samples were positive for EGFR expression. On multivariate analysis we found patients who took chemotherapy and with good performance status (Karnofsky score >65 and Eastern Cooperative Oncology Group >2.5) had better survival at 6 months.Conclusions: Patients with EGFR positivity had better survival with chemotherapy but worse with radiotherapy. Patients who took chemotherapy and had good performance status had better survival on multivariate analysis. We didn’t find any correlation between EGFR positivity and poor survival.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Olga V. Kovaleva ◽  
Daniil Romashin ◽  
Irina B. Zborovskaya ◽  
Mikhail M. Davydov ◽  
Murat S. Shogenov ◽  
...  

Recent research on cancer-associated microbial communities led to the accumulation of data on the interplay between bacteria, immune and tumor cells, the pathways of bacterial induction of carcinogenesis, and its meaningfulness for medicine. Microbial communities that have any kind of impact on tumor progression and microorganisms associated with tumors have been defined as oncobiome. Over the last decades, a number of studies were dedicated to Helicobacter pylori and its role in the progression of stomach tumors, so this correlation can be regarded as proven. Involvement of bacteria in the induction of lung cancer has been largely ignored for a long time, though some correlations between this type of cancer and lung microbiome were established. Despite the fact that in the present the microbial impact on lung cancer progression has many confirmations, the underlying mechanisms are poorly understood. Microorganisms can contribute to tumor initiation and progression through production of bacteriotoxins and other proinflammatory factors. The purpose of this review is to organize the available data on lung cancer microbiome and its role in malignant tumor progression.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Xianming Fei ◽  
Huan Wang ◽  
Wufeng Yuan ◽  
Mingyi Wo ◽  
Lei Jiang

Activation of blood coagulation contributes to cancer progression. Tissue factor pathway inhibitor-1 (TFPI-1) is the main inhibitor of extrinsic coagulation pathway. The aim of this study is to assess the predicting significance of TFPI-1 for thrombotic complication and metastasis in lung cancer patients. Total of 188 non-small cell lung cancer (NSCLC) patients were included in this study. Plasma TFPI-1, D-dimer (D-D), antithrombin (AT), Fibrinogen (Fbg), and coagulating factor VIII activity (FVIII:C) were measured. In NSCLC patients, significantly decreased TFPI-1 and AT and increased D-D, Fbg, and FVIII:C levels were observed, and there was a significant correlation between TFPI-1 and other hemostatic parameters (P<0.001, resp.). NSCLC patients with deep venous thrombosis (DVT) or metastasis had significantly lower TFPI-1 levels than those without DVT or metastasis (P<0.01, resp.). Multivariate regression revealed that TFPI-1 acted as a predictor for DVT or tumor metastasis in NSCLC patients [OR: 4.15 or 3.28,P<0.05, resp.]. The area under ROC curve of TFPI-1 was 0.905 (95% CI, 0.842~0.967) or 0.828 (95% CI, 0.742~0.915) for predicting DVT or metastasis (P<0.001, resp.). The optimal point of TFPI-1 was 57.7 or 54.3 ng/mL for predicting DVT or metastasis, respectively. Combination of TFPI-1 and D-D measurements can improve the predicting power for DVT or metastasis in NSCLC patients. Our findings suggested that TFPI-1 was a valuable predictor of DVT and tumor metastasis in NSCLC patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Dong ◽  
Eric S. Chen ◽  
Chen Zhao ◽  
Chengcheng Jin

Commensal microbiota has emerged as an essential biomarker and regulator of both tumorigenesis and response to cancer therapy. However, our current knowledge about microbiota in cancer has been largely limited to intestinal microbiota. As a mucosal organ harboring one of the largest surface areas in the body, the lung is exposed to a variety of microbes through inhalation and micro-aspiration, and is colonized by a diverse bacterial community in both physiological and pathological conditions. Importantly, increasing evidence has linked the lung microbiome to cancer development. Studies in lung cancer patients and mouse models have revealed tumor-associated dysregulation of the local microbiome in the lung, which in turn impacts cancer progression by shaping the tumor microenvironment and modulating the activity of tumor-infiltrating immune cells. These findings not only provide novel mechanistic insight into the biology of lung cancer but also shed light on new therapeutic targets and strategies for lung cancer prevention and treatment. The goal of this review is to discuss the key findings, remaining questions, and future directions in this new and exciting field.


Author(s):  
Xin Lyu ◽  
Hui Zheng ◽  
Xu Wang ◽  
Heyu Zhang ◽  
Lu Gao ◽  
...  

Oral microbiota is constantly changing with the host state, whereas the oral microbiome of chronic erythematous candidiasis remains poorly understood. The aim of this study was to compare oral microbial signatures and functional profiling between chronic erythematous candidiasis and healthy subjects. Using shotgun metagenomic sequencing, we analyzed the microbiome in 12 chronic erythematous candidiasis, 12 healthy subjects, and 2 chronic erythematous candidiasis cured by antifungal therapy. We found that the salivary microbiota of chronic erythematous candidiasis was significantly different from that of healthy subjects. Among them, Rothia mucilaginosa and Streptococcus mitis were the most abundant disease-enriched species (Mann-Whitney U-test, P &lt; 0.05). In addition, co-occurrence network analysis showed that C. albicans formed densely connected modules with oral bacterial species and was mainly positive connected to Streptococcus species. Furthermore, we investigated the functional potentials of the microbiome and identified a set of microbial marker genes associated with chronic erythematous candidiasis. Some of these genes enriching in chronic erythematous candidiasis are involved in eukaryotic ribosome, putative glutamine transport system, and cytochrome bc1 complex respiratory unit. Altogether, this study revealed the changes of oral microbial composition, the co-occurrence between C. albicans and oral bacteria, as well as the changes of microbial marker genes during chronic erythematous candidiasis, which provides evidence of oral microbiome as a target for the treatment and prevention of chronic erythematous candidiasis.


2021 ◽  
Author(s):  
Chu Chun Yu ◽  
Chia Yu Chu ◽  
Yeur Hur Lai ◽  
Jui Chun Chan ◽  
Yen Ju Chen ◽  
...  

Abstract Objective: To examine the difference in levels of fear of cancer progression (FoP), anxiety, depression between presence/absence of the target-adverse events (AEs); and to examine the differences in incidence rate of AEs and FoP, anxiety, and depression among three generations of EGFR-TKIs therapy (first, gefitinib and erlotinib [G1]; second, afatinib [G2]; third, osimertinib [G3]) in non-small-cell lung cancer (NSCLC) patients.Methods: A cross-sectional study design. NSCLC patients (n=128) were recruited from a medical center in Taiwan. A set of structured questionnaires assessing AEs, FoP, anxiety and depression. Results: Parts of AEs, such as photosensitivity, paronychia, and alopecia, exhibited significantly higher levels of FoP, anxiety, and depression. Less patients experienced AEs in the G3 group than those in the G1 or G2 group but still reported experiencing itching, dry skin with grade 3 severity. The incidence rates of mouth/throat sores, and cheilosis/cheilitis in the G2 group was significantly higher than those in the G1 or G3 group. The incidence rate of FoP, anxiety and depression were 13.8-26.3%, 23.8-40.4% and 16.7-42.1%, respectively.Conclusions: The priorities of care among three generations of EGFR-TKIs in patients with NSCLC were established. FoP, anxiety and depression were present among different targeted therapies and require further attention.


Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1200
Author(s):  
Panagiotis Giannos ◽  
Konstantinos S. Kechagias ◽  
Annamaria Gal

The progression of non-small cell lung cancer (NSCLC) is linked to epithelial-mesenchymal transition (EMT), a biologic process that enables tumor cells to acquire a migratory phenotype and resistance to chemo- and immunotherapies. Discovery of novel biomarkers in NSCLC progression is essential for improved prognosis and pharmacological interventions. In the current study, we performed an integrated bioinformatics analysis on gene expression datasets of TGF-β-induced EMT in NSCLC cells to identify novel gene biomarkers and elucidate their regulation in NSCLC progression. The gene expression datasets were extracted from the NCBI Gene Expression Omnibus repository, and differentially expressed genes (DEGs) between TGF-β-treated and untreated NSCLC cells were retrieved. A protein-protein interaction network was constructed and hub genes were identified. Functional and pathway enrichment analyses were conducted on module DEGs, and a correlation between the expression levels of module genes and survival of NSCLC patients was evaluated. Prediction of interactions of the biomarker genes with transcription factors and miRNAs was also carried out. We described four protein clusters in which DEGs were associated with ubiquitination (Module 1), regulation of cell death and cell adhesions (Module 2), oxidation-reduction reactions of aerobic respiration (Module 3) and mitochondrial translation (Module 4). From the module genes, we identified ten prognostic gene biomarkers in NSCLC. Low expression levels of KCTD6, KBTBD7, LMO7, SPSB2, RNF19A, FOXA2, DHTKD1, CDH1 and PDHB and high expression level of KLHL25 were associated with reduced overall survival of NSCLC patients. Most of these biomarker genes were involved in protein ubiquitination. The regulatory network of the gene biomarkers revealed their interaction with tumor suppressor miRNAs and transcription factors involved in the mechanisms of cancer progression. This ten-gene prognostic signature can be useful to improve risk prediction and therapeutic strategies in NSCLC. Our analysis also highlights the importance of deregulation of ubiquitination in EMT-associated NSCLC progression.


2021 ◽  
Author(s):  
Gwan Woo Ku ◽  
Yujin Kang ◽  
Seong-Lan Yu ◽  
Joonghoon Park ◽  
Sejin Park ◽  
...  

Abstract Background lncRNAs have important roles in regulating cancer biology. Accumulating evidence has established a link between the dysregulation of lncRNAs and microRNA in cancer progression. In previous studies, miR-7-5p has been found to be significantly down-regulated in mesenchymal-like lung cancer cell lines and directly regulated EGFR. In this work, we investigated the lncRNA partner of miR-7-5p in the progression of lung cancer.Methods We investigated the expression of miR-7-5p and the lncRNA after transfection with an miR-7-5p mimics using a microarray. The microarray results were validated using quantitative real time-polymerase Chain Reaction (qRT-PCR). The regulatory effects of lncRNA on miR-7-5p and its target were evaluated by changes in the expression of miR-7-5p after transfection with siRNAs for lncRNA and the synthesis of full-length lncRNA. The effect of miR-7-5p on lncRNA and the miRNA target was evaluated after transfection with miRNA mimic and inhibitor. The role of lncRNA in cancer progression was determined using invasion and migration assays. The level of lncRNA and EGFR in lung cancer and normal lung tissue was analyzed using TCGA data.Results We found that LINC00240 was downregulated in lung cancer cell line after miR-7-5p transfection with an miR-7-5p mimic. Further investigations revealed that the knockdown of LINC00240 induced the overexpression of miR-7-5p. The overexpression of miR-7-5p diminished cancer invasion and migration. The EGFR expression was down regulated after siRNA treatment for LINC00240. Silencing LINC00240 suppressed the invasion and migration of lung cancer cells, whereas LINC00240 overexpression exerted the opposite effect. The lower expression of LINC00240 in squamous lung cancer was analyzed using TCGA data.Conclusions Taken together, LINC00240 acted as a sponge for miR-7-5p and induced the overexpression of EGFR. LINC00240 may represent a potential target for the treatment of lung cancer.


Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1361
Author(s):  
Ping-Chih Hsu ◽  
Cheng-Ta Yang ◽  
David M. Jablons ◽  
Liang You

The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.


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