scholarly journals Metatranscriptomic Analysis of Human Lung Metagenomes from Patients with Lung Cancer

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1458
Author(s):  
Ya-Sian Chang ◽  
Ming-Hung Hsu ◽  
Siang-Jyun Tu ◽  
Ju-Chen Yen ◽  
Ya-Ting Lee ◽  
...  

This study was designed to characterize the microbiomes of the lung tissues of lung cancer patients. RNA-sequencing was performed on lung tumor samples from 49 patients with lung cancer. Metatranscriptomics data were analyzed using SAMSA2 and Kraken2 software. 16S rRNA sequencing was also performed. The heterogeneous cellular landscape and immune repertoires of the lung samples were examined using xCell and TRUST4, respectively. We found that nine bacteria were significantly enriched in the lung tissues of cancer patients, and associated with reduced overall survival (OS). We also found that subjects with mutations in the epidermal growth factor receptor gene were less likely to experience the presence of Pseudomonas. aeruginosa. We found that the presence of CD8+ T-cells, CD4+ naive T-cells, dendritic cells, and CD4+ central memory T cells were associated with a good prognosis, while the presence of pro B-cells was associated with a poor prognosis. Furthermore, high clone numbers were associated with a high ImmuneScore for all immune receptor repertoires. Clone numbers and diversity were significantly higher in unpresented subjects compared to presented subjects. Our results provide insight into the microbiota of human lung cancer, and how its composition is linked to the tumor immune microenvironment, immune receptor repertoires, and OS.

2020 ◽  
Author(s):  
Julian Ramelow ◽  
Christopher Brooks ◽  
Li GaO ◽  
Abeer A Almiman ◽  
Terence M Williams ◽  
...  

Abstract BackgroundLung cancer is the number one cancer killer worldwide. A major impediment to progress in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed. Mutations of the tumor suppressor gene TP53 are among the most common alterations in human lung cancers.MethodsPreviously, we developed a line of lung cancer mouse model where mutant human TP53-273H is expressed in a lung specific manner in FVB/N background. To investigate whether the human TP53 mutant has a similar oncogenic potential when it is expressed in another strain of mouse, we crossed the FVB/N-SPC-TP53-273H mice to A/J strain and created A/J-SPC-TP53-273H transgenic mice. We then compared lung tumor formation between A/J-SPC-TP53-273H and FVB/N-SPC-TP53-273H.ResultsWe found the TP53-273H mutant gene has a similar oncogenic potential in lung tumor formation in both mice strains, although A/J strain mice have been found to be a highly susceptible strain in terms of carcinogen-induced lung cancer. Both transgenic lines survived more than 18 months and developed age related lung adenocarcinomas. With micro CT imaging, we found the FVB-SPC-TP53-273H mice survived more than 8 weeks after initial detection of lung cancer, providing a sufficient window for evaluating new anti-cancer agents.ConclusionsOncogenic potential of the most common genetic mutation, TP53-273H, in human lung cancer is unique when it is expressed in different strains of mice. Our mouse models are useful tools for testing novel immune check point inhibitors or other therapeutic strategies in treatment of lung cancer.


2020 ◽  
Vol 10 ◽  
Author(s):  
Yongyuan Chen ◽  
Zhongwei Xin ◽  
Lijian Huang ◽  
Lufeng Zhao ◽  
Shijie Wang ◽  
...  

Stem Cells ◽  
2008 ◽  
Vol 26 (10) ◽  
pp. 2523-2530 ◽  
Author(s):  
Haruki Chiba ◽  
Genicihro Ishii ◽  
Ta-Kashi Ito ◽  
Kazuhiro Aoyagi ◽  
Hiroki Sasaki ◽  
...  

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Huan Liu ◽  
Qian Cheng ◽  
Dong-sheng Xu ◽  
Wen Wang ◽  
Zheng Fang ◽  
...  

Abstract Background Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in more than 20 human malignancies, among which lung cancer is the leading cause of cancer-associated deaths worldwide. Thus, the mechanism of CXCR7 in the progression of lung cancer is urgently needed. Methods First, we explored CXCR4 and CXCR7 expression in human lung cancer specimens and cell lines by immunohistochemistry, western blot and flow cytometry. Then, we chose the human lung adenocarcinoma cell line A549 that stably overexpressed CXCR7 through the way of lentivirus-mediated transduction. Next, “wound healing” assay and transwell assay were applied to compare the cell migration and invasion ability, and stripe assay was used to evaluate the cell polarization. Last, our team established a mouse xenograft model of human lung cancer and monitored tumor proliferation and metastasis by firefly luciferase bioluminescence imaging in SCID/Beige mice. Results In clinical lung cancer samples, CXCR7 expression was almost not detected in normal tissue but upregulated in lung tumor tissue, whereas, CXCR4 was highly expressed in both normal and tumor tissues. Furthermore, overexpression of CXCR7 enhanced A549 cell migration and polarization in vitro. Besides, mouse xenograft model of human lung cancer showed that CXCR7 promoted primary lung tumor’s growth and metastasis to the second organ, such as liver or bone marrow in SCID/Beige mice in vivo. Conclusions This study describes the multiple functions of CXCR7 in lung cancer. Thus, these results suggest that CXCR7 may be a malignancy marker and may provide a novel target for anticancer therapy.


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