Characteristics of Microbiome in Lung Adenocarcinoma Tissue from Patients in Southwestern China

Abstract Background:Increasing evidences have unveiled the connection between microbiome and lung cancer. This study aims to identify the characteristics of microbial communities in the lung cancer tissues from patients in southwestern China, and to compare the distinct microbial genes at different clinical stages of lung cancer for uncovering potential immunotherapy targets.Methods:Forty samples of primary lung adenocarcinoma tissue were performed by 16S rRNA gene sequencing. The subjects were grouped according to TNM stages (T and N group), clinical stage and smoke status. To identify the taxa composition of each sample, Operational Taxonomic Units (OTUs) were classified on the Effective Tags with 97% identity. The linear discriminant analysis effect size (LEfSe) method was utilized to compare relative abundances of all bacterial taxa between non-metastasis group and metastasis group. The Shannon index of the 97% identity OTUs was calculated to evaluate alpha diversity. Beta diversity measurement was calculated using Principal Co-ordinates Analysis (PCoA).Results:A total of 951 OTUs were identified in the cancer tissues, including 224 overlapping genera. No significant difference has been found in the alpha diversity within all the groups. Beta diversity was significantly different in N group, T group and clinical stage group. By LEfSe analysis, nine differential species were identified in the N group, of which the relative abundance of genus Bifidobacterium was 10.78%±11.59% in the N0 group and 20.15%±13.44% in the N+ group (p<0.05). In the T1 and T2 group, the LEfSe result identified 4 phylum and 10 genera. The differential genera were Moraxella, Dolosigranulum, Corynebacteriaceae and Citrobacter in the T2 group and Bifidobacterium, Alistipes, Akkermansia, Blautia, Lactobacillus as well as Facelibacterium in the T1 group. Differential bacterial composition and abundance were also observed in the clinical stage group.Conclusions:In conclusion, by 16S RNA sequencing, we identified dominant species of lung cancer tissue in different groups of AD patients. Bifidobacterium plays important role both in lymph node metastasis and tumor progression, which could provide specific immunotherapy strategy for lung cancer.

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Aberrant β-catenin activity in hepatoid adenocarcinoma of the stomach

Current Molecular Medicine ◽

10.2174/0929867327666200522215607 ◽

2020 ◽

Vol 20 ◽

Author(s):

Nan Wang ◽

Rui Kong ◽

Wei Han ◽

Jie Lu

Keyword(s):

Hepatocellular Carcinoma ◽

Pearson Correlation ◽

Clinicopathological Characteristics ◽

Cancer Tissue ◽

Hepatoid Adenocarcinoma ◽

Tumor Initiating Cells ◽

Significant Difference ◽

Diagnostic Confusion ◽

Hematoxylin And Eosin ◽

Cancer Tissues

Background: Hepatoid adenocarcinoma of the stomach (HAS) has been recognized as a rare primary gastric tumor characterized by hepatocellular carcinoma-like histology. HAS often causes diagnostic confusion with conventional gastric adenocarcinoma (CGA) due to the difficulty to detect hepatoid differentiation solely based on findings from hematoxylin and eosin (H&E) staining. Hence, HAS should be distinguished from solid-type CGA based on their different biological behaviors. β-catenin is highly expressed in hepatocellular carcinoma (HCC), which is involved in the maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. Methods and Results: Given the dearth of HAS cases, systematic examination of the expression of β-catenin in HAS remains under-explored. In this study, 14 cases were subjected to immunostaining with with AFP, β-catenin, glypican3, hepar-1 and CerbB-2. In parallel, the clinicopathological characteristics of these patients were collected. We detected statistically significant difference in the expression of β-catenin (P = 0.000), glypican3 (P = 0.019), and hepar-1 (P = 0.007) between HAS cancer tissues and the adjacent non-cancerous tissues. Furthermore, a significant correlation was observed between the expression of β-catenin in HAS cancer tissue and adjacent tissue (Pearson correlation coefficient: 0.686, P = 0.007). Moreover, in cancer tissues, a significant correlation was observed between the expression of β-catenin and survival time (Spearman correlationcoefficient= - 0.482, P = 0.003). However, we found the expression of β-catenin did not correlate with the degree of tumor differentiation and tumor size, age, gender, serum AFP levels, microinvasion, and metastasis (P > 0.05). Conclusion: Our findings establish β-catenin as a useful marker that can distinguish HAS from CGA and may improve the early diagnosis to guide the appropriate and timely treatment of HAS patients.

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MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF

Biochemistry and Cell Biology ◽

10.1139/bcb-2018-0301 ◽

2019 ◽

Vol 97 (4) ◽

pp. 415-422 ◽

Cited By ~ 3

Author(s):

Linqing Pan ◽

Zhipeng Tang ◽

Lina Pan ◽

Ranran Tang

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Signaling Pathways ◽

Histological Grade ◽

Clinical Stage ◽

Luciferase Reporter ◽

Advanced Clinical Stage ◽

Mesenchymal Transition ◽

Adenocarcinoma Cell

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3′-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3′-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K–AKT and epilthelial–mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K–AKT and EMT signaling pathways in human lung cancers.

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Role of DACH1 on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells

Current Molecular Medicine ◽

10.2174/1566524021666210119094633 ◽

2021 ◽

Vol 21 ◽

Author(s):

Junjie Yu ◽

Ping Jiang ◽

Ke Zhao ◽

Zhiguo Chen ◽

Tao Zuo ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Tumor Cells ◽

Human Lung ◽

A549 Cells ◽

Cancer Tissue ◽

Lung Cancer Tissue ◽

Adenocarcinoma Cells ◽

Human Lung Adenocarcinoma Cells ◽

Lung Adenocarcinoma Cells

Objective: To investigate DACH1 protein expression in lung cancer tissue and matched paracancerous tissue, and explore its effect on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells (HLACs). Methods: Tumor tissue and matched paracancerous tissue was collected from 46 patients with pathologically diagnosed lung cancer. RT-PCR was perfomed to detect DACH1 mRNA expression and immunohistochemistry to measured DACH1 protein expression. To determine the effect of DACH1 on lung cancer behavior, small interfering RNA (siRNA) was used to silence DACH1 expression in A549 cells. The impact on the proliferation of tumor cells was then observed by MTT assay, changes in the invasion of tumor cells were identified using transwell chamber assay, and the effects on apoptosis in the cell line were detected using flow cytometry. Results: The expression of DACH1 mRNA and DACH1 protein were significantly decreased in lung cancer tissue versus matched paracancerous control tissue. Silencing of DACH1 expression in A549 cells significantly enhanced cell proliferation, significantly increased cell invasion and significantly reduced spontaneous apoptosis. Conclusion: DACH1 is downregulated in lung adenocarcinoma tissue. In vitro assessment shows that DACH1 functions as a tumor suppressor, suggesting its potential use as new target for lung cancer treatment.

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Diagnostic value of α-enolase expression and serum α-enolase autoantibody levels in lung cancer

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37562016000000241 ◽

2018 ◽

Vol 44 (1) ◽

pp. 18-23 ◽

Cited By ~ 3

Author(s):

Lihong Zhang ◽

Hongbin Wang ◽

Xuejun Dong

Keyword(s):

Lung Cancer ◽

Lung Disease ◽

Cancer Patients ◽

Clinical Stage ◽

Diagnostic Value ◽

Smoking History ◽

Lung Cancer Patients ◽

Pathological Classification ◽

Cancer Tissues ◽

Antibody Levels

ABSTRACT Objective: To investigate the diagnostic value of α-enolase (ENO1) and serum ENO1 autoantibody levels in lung cancer. Methods: Immunohistochemistry staining and ELISA were performed to detect ENO1 expression in lung tissue and serum ENO1 autoantibody levels, respectively. Results: The expression of ENO1 was higher in lung cancer tissues than in benign lung disease tissues (p < 0.001). The proportion of lung cancer samples expressing ENO1 was not significantly different among the various pathological classification groups. The proportion of samples expressing ENO1 was higher in lung cancer patients in stages I/II than in those in stages III/IV (χ2 = 5.445; p = 0.018). The expression of ENO1 in lung cancer tissues was not associated with age, gender, or smoking history. Serum ENO1 antibody levels were significantly higher in the lung cancer group than in the benign lung disease and control groups (p < 0.001). The differences among the pathological classification groups were not statistically significant. Serum ENO1 antibody levels were also in lung cancer patients in stages I/II than in those in stages III/IV (p < 0.01). Serum ENO1 antibody levels were not associated with age, gender, or smoking history in lung cancer patients. The ROC curve representing the diagnosis of lung cancer based on ENO1 antibody levels had an area under the curve of 0.806. Conclusions: Our results suggest that high levels of ENO1 are associated with the clinical stage of lung cancer and that ENO1 expression and its serum autoantibody levels show diagnostic value in lung cancer.

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Epitope mapping of epidermal growth factor receptor (EGFR) in lung cancer using immunohistochemistry: Fine tuning the protocols

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21162 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21162-21162

Author(s):

J. TIMAR ◽

K. Derecskei ◽

B. Dome ◽

J. Moldvay

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Ligand Binding ◽

Lung Adenocarcinoma ◽

Growth Factor Receptor ◽

Fine Tuning ◽

Antigen Retrieval ◽

Egfr Expression ◽

Lung Adenocarcinomas ◽

Cancer Tissues

21162 Background: Until now, immunohistochemistry was not able to become a reliable diagnostic approach for EGFR targeted therapies. The golden standard of the determination of EGFR protein expression in paraffin embedded cancer tissues is the EGFRpharmDXtm kit. Methods: Here we show data based on analysis of 110 lung adenocarcinomas, that the recommended protocol may not be optimal for ideal performance of the immunodetection, since microwave retrieval, extended primary antibody-incubation time and replacement of the developer reagent converted four EGFR-negative tumor into EGFR protein positive out of eight lung adenocarcinoma cases. Protocol modification improved the performance of another widely used EGFR-kit, Ventana's CONFIRM, where replacement of the protease antigen retrieval with microwave cooking converted several EGFR-negative tumors to strongly positive. Meanwhile both EGFR-kits detect EGFR expression (juxtamembrane domain) but do not provide information on the expression of epitopes critical from the point of view of targeted therapy. Results: We have developed two protocols, which can detect the ligand-binding (AB-10, BioMarkers) and C-terminal (AB- 335, Biogenex) cytoplasmic domains of the EGFR protein in paraffin embedded lung cancer tissues. We have shown, based on the analysis of more than 110 lung adenocarcinoma tissues, that the ligand binding domain of EGFR is rarely expressed while the C-terminal domain is ubiquitously expressed in EGFR-PharmDX and CONFIRM-positive cancers. The biological activity of EGFR can be characterized either by autophosphorylation of the receptor or by detection of divers phosphorylated downstream signaling components. We have found that unlike p1086 (detected by a Zymed antibody), the p1173 site of EGFR (identified by a rabbit monoclonal of Epitomics) can be detected 27/110 paraffin embedded lung adenocarcinomas. Conclusions: Using the tested antibody panel we can reliably determine the EGFR protein expression in paraffin embedded (lung)cancer tissues. This work was supported by Ministry of Education (NKFP1a-0024–05). No significant financial relationships to disclose.

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Oncologic outcomes of segmentectomy versus lobectomy for radiologically aggressive small-sized lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.8525 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 8525-8525

Author(s):

Atsushi Kamigaichi ◽

Yasuhiro Tsutani ◽

Takahiro Mimae ◽

Yoshihiro Miyata ◽

Kentaro Imai ◽

...

Keyword(s):

Computed Tomography ◽

Lung Cancer ◽

Clinical Stage ◽

Multivariable Analysis ◽

Standardized Uptake Value ◽

Ground Glass Opacity ◽

Oncologic Outcomes ◽

Smoking History ◽

High Resolution Computed Tomography ◽

Significant Difference

8525 Background: Despite increasing evidence of favorable outcomes after segmentectomy for indolent lung cancer, such as ground glass opacity-dominant tumors, the adaptation of segmentectomy for radiologically aggressive lung cancer remains controversial. We attempted to elucidate oncologic outcomes after segmentectomy for radiologically aggressive lung cancer. Methods: Data from a multicenter database of 1353 patients with completely resected clinical Stage IA1–IA2 lung cancer at three institutions were retrospectively analyzed to identify radiologically aggressive lung cancer and compare outcomes of segmentectomy versus lobectomy in patients with radiologically aggressive lung cancer using propensity score matching. Results: Multivariable analysis showed that consolidation to maximum tumor (C/T) ratio on preoperative high-resolution computed tomography ( P= 0.037) and maximum standardized uptake value (SUVmax) on 18-fluorodeoxyglucose positron emission tomography/computed tomography ( P= 0.029) were independent predictors of recurrence-free survival (RFS). The criteria for radiologically aggressive lung cancer were determined as C/T ratio ≥ 0.8 or SUVmax ≥ 2.5, for which 522 patients were identified. RFS and overall survival (OS) were significantly worse in patients with aggressive lung cancer (5-year RFS, 83.3%; 5-year OS, 89.4%) than in those without the same (5-year RFS, 97.0%; P< 0.0001; 5-year OS, 97.3%; P< 0.0001). Among patients with aggressive lung cancer, no significant difference in RFS and OS was found between those undergoing lobectomy (n = 392) (5-year RFS, 81.3%; 5-year OS, 88.3%) and segmentectomy (n = 130) (5-year RFS, 90.0%; P= 0.33; 5-year OS, 92.3%; P= 0.76). Among the 111 pairs propensity matched for age, sex, smoking history, solid tumor size, C/T ratio, SUVmax, tumor location, clinical stage, and histology, similar RFS and OS were found between those undergoing lobectomy (5-year RFS, 83.3%; 5-year OS, 88.3%) and segmentectomy (5-year RFS, 90.9%; P= 0.92; 5-year OS, 94.5%). Conclusions: For radiologically aggressive small-sized lung cancer, oncologic outcomes of segmentectomy were equivalent to those of lobectomy.

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Non-small cell lung cancer microbiota characterization: Prevalence of enteric and potentially pathogenic bacteria in cancer tissues

PLoS ONE ◽

10.1371/journal.pone.0249832 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249832

Author(s):

Nathan Dumont-Leblond ◽

Marc Veillette ◽

Christine Racine ◽

Philippe Joubert ◽

Caroline Duchaine

Keyword(s):

Lung Cancer ◽

Pathogenic Bacteria ◽

Amplicon Sequencing ◽

Healthy Tissue ◽

Cancer Tissue ◽

Rrna Gene ◽

Variable Degree ◽

Tissue Samples ◽

Small Cancer ◽

Cancer Tissues

Following recent findings linking the human gut microbiota to gastrointestinal cancer and its treatment, the plausible relationship between lung microbiota and pulmonary cancer is explored. This study aims at characterizing the intratumoral and adjacent healthy tissue microbiota by applying a 16S rRNA gene amplicon sequencing protocol to tissue samples of 29 non-small cancer patients. Emphasis was put on contaminant management and a comprehensive comparison of bacterial composition between cancerous and healthy adjacent tissues of lung adenocarcinoma and squamous cell carcinoma is provided. A variable degree of similarity between the two tissues of a same patient was observed. Each patient seems to possess its own bacterial signature. The two types of cancer tissue do not have a distinct bacterial profile that is shared by every patient. In addition, enteric, potentially pathogenic and pro-inflammatory bacteria were more frequently found in cancer than healthy tissue. This work brings insights into the dynamic of bacterial communities in lung cancer and provides prospective data for more targeted studies.

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Changes of the expression of Lewis blood group antigens in glycoproteins of renal cancer tissues.

Acta Biochimica Polonica ◽

10.18388/abp.2013_1975 ◽

2013 ◽

Vol 60 (2) ◽

Cited By ~ 1

Author(s):

Małgorzata Borzym-Kluczyk ◽

Iwona Radziejewska

Keyword(s):

Sialic Acid ◽

Blood Group ◽

Tumor Development ◽

Renal Tissue ◽

Cancer Tissue ◽

Blood Group Antigens ◽

Lewis Blood Group ◽

Significant Difference ◽

Cancer Tissues ◽

Sialyl Lewisa

Sialic acid and sialyl Lewisa/x are found on N- and O-glycans of many human malignant cells. Carbohydrate antigens can be used as tumor markers, and an increase of their levels in cancer cells is associated with tumor progression. The aim of this study was to assess the level of some Lewis blood group antigens on glycoproteins in tumor (cancer tissue), intermediate zone (adjacent to tumor tissue), and normal renal cortex/medulla (uninvolved by tumor). The study was performed on tissues taken from 30 patients. Relative amounts of sugar structures of proteins with molecular masses above 30 kDa were determined by ELISA-like test with biotinylated lectins: MAA (Maackia amurensis), SNA (Sambucus nigra), and monoclonal antibodies anti-sialyl Lewisa/x.∙ Higher expression of all examined structures was revealed in cancer tissues. Significant increases were observed for sialic acid linked α 2-3 in cancer tissues when compared to healthy ones and also among intermediate and healthy tissues. The sialic acid linked α 2-6 and sialyl Lewisx structures were significantly increased in cancerous cells when compared to normal and intermediate renal tissue. In case of sialyl Lewisa antigen, a significant difference was discovered between normal and intermediate tissue. Our results confirm that the examined Lewis antigens can be involved in tumor development. Their increase in cancer tissues can suggest their specific role in the process.

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FAM83A-AS1 Promotes Tumor Progression Through MET Signaling in Lung Adenocarcinoma

10.21203/rs.3.rs-616083/v1 ◽

2021 ◽

Author(s):

Shengbin Bai ◽

Huijie Zhao ◽

Xaofei Zeng ◽

Baoyue Lin ◽

Yinghan Wang ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Functional Studies ◽

Cycle Arrest ◽

Elevated Expression ◽

Lung Cancer Therapy ◽

Prognosis Marker ◽

Cancer Tissues

Abstract Background Studies demonstrate that long non-coding RNAs (lncRNAs) play critical roles in the occurrence and development of cancer. However, many of the molecular mechanisms underlying lncRNAs role in this process remains unclear. Methods Here, we analyzed lncRNA expression in lung cancer tissues based on RNA-Seq analysis and found that lncRNA FAM83A-AS1 was one of the top up-regulated lncRNAs in lung adenocarcinoma and elevated expression of FAM83A-AS1 was significantly associated with poor patient survival. We validated these results using RT-PCR and an independent cohort of lung cancer. Results Functional studies indicated that knockdown of FAM83A-AS1 decreased cell proliferation, colony formation, migration and invasion in H1299 and H838 lung cancer cells. Knockdown of FAM83A-AS1 induced the autophagy and cell cycle arrest at G2. Mechanistically, we found that MET, p62 and phosphor S6K proteins were decreased upon FAM83A-AS1 knockdown. Conclusion In conclusion, FAM83A-AS1 may have potential as a diagnosis/prognosis marker and its oncogenic role could lead to potential targeting for lung cancer therapy.

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Angiogenic marker associated with resistance to neoadjuvant chemoradiotherapy in rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11030 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11030-11030 ◽

Cited By ~ 1

Author(s):

Hanjo Kim ◽

Min Young Lee ◽

Tae Sung Ahn ◽

Jina Yun ◽

Kyoungha Kim ◽

...

Keyword(s):

Rectal Cancer ◽

Growth Factor ◽

Clinical Stage ◽

Antiangiogenic Therapy ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Angiogenic Factors ◽

Cancer Tissue ◽

Expression Rate ◽

Cancer Tissues

11030 Background: The ability to achieve pathologic down staging after neoadjuvant chemoradiotherapy (CRT) is correlated with improved survival. However, there is no effective method of predicting which patients will response to neoadjuvant CRT. Neoadjuvant CRT can change the expression of angiogenic factors. However, little is known about its possible changes in response to preoperative CRT. We examined the expression of angiogenic factors in rectal cancer tissues before preoperative CRT and after surgery. Methods: Fifty five patients with locally advanced rectal cancer were studied. All patients were given preoperative CRT of 5040 cGy for 5-6 weeks with concurrent administration of 5-fluorouracil and leucovorin. Surgical resection was performed 6–8 weeks later in all patients. Immunohistochemical staining for angiogenenic markers (vascular endothelial growth factor [VEGF], placenta growth factor [PLGF], hypoxia inducible factor 1α [HIF 1α], stromal cell derived factor [SDF 1α]) were performed on specimens obtained before preoperative CRT and after surgery. A semiquantitative-immunohistochemical score established from the extension and intensity of the angiogenic factors was used for analysis. Results: The positive expression rate of VEGF, PLGF, SDF 1α, and HIF 1α was 56.4% (31/55), 65.5% (36/55), 70.9% (39/55), and 47.3% (26/55), respectively. The expression rate of VEGF, PLGF, SDF 1α, and HIF 1α was increased by 3.6% (2/55), 7.3% (4/55), 30.9% (17/55), and 1.8% (1/55) after neoadjuvant CRT, respectively. Expression of VEGF, PLGF, and HIF 1α protein was downregulated after neoadjuvant CRT in the rectal cancer tissues (P < 0.001, P = 0.001, P = 0.044, respectively). However, SDF 1α was upregulated after neoadjuvant CRT (P < 0.001). And also, upregulated expression of SDF 1α after neoadjuvant CRT was significantly associated with resistance to CRT (P = 0.035). However, SDF 1α showed no correlation with other clinical factors (age, sex, clinical stage). Conclusions: Expression of SDF-1α was increased in the rectal cancer tissue after neoadjuvant CRT, as well as has been associated with CRT resistance. Our data suggests that SDF 1α should be evaluated as new target for antiangiogenic therapy.

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