scholarly journals CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 252 ◽  
Author(s):  
Kentaro Inamura ◽  
Yasuyuki Shigematsu ◽  
Hironori Ninomiya ◽  
Yasuhiro Nakashima ◽  
Maki Kobayashi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Smoking Status ◽  
High Expression ◽  
Nucleotide Polymorphisms ◽  
Tumor Associated Macrophages ◽  
Expression Levels ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Prognostic Association

CSF1R-expressing tumor-associated macrophages (TAMs) induce a tumor-promoting microenvironment by regulating immunity. Evidence demonstrates that the expression and single nucleotide polymorphisms of CSF1R relate with survival and risk of lung cancer in never smokers. However, no previous studies have examined the association of CSF1R expression in TAMs with mortality or whether the prognostic association differs according to smoking status in lung adenocarcinoma. Quantitative phosphor-integrated dot staining was used to precisely assess CSF1R expression in TAMs. Using 195 consecutive cases of lung adenocarcinoma, we examined the association of CSF1R expression with mortality and whether the prognostic association differs according to smoking status. We observed high expression levels of CSF1R in TAMs in 65 of 195 (33%) cases of lung adenocarcinoma. High expression levels of CSF1R were associated with high lung cancer-specific mortality (log-rank p = 0.037; hazard ratio (HR) = 1.61, 95% confidence interval (CI) = 1.02−2.52, p = 0.043). This prognostic association differed according to smoking status (p for interaction = 0.049, between never-smoking and ever-smoking patients). The association between high expression levels of CSF1R and lung cancer-specific mortality was stronger in never-smoking patients (log-rank p = 0.0027; HR = 2.90, 95% CI = 1.41−6.11, p = 0.0041) than in ever-smoking patients (log-rank p = 0.73; HR = 1.11, 95% CI = 0.59−2.00, p = 0.73). The findings suggest that CSF1R-expressing TAMs may exert stronger tumor-promoting immunity in never-smoking patients with lung adenocarcinoma and serve as a therapeutic target in precision immunotherapies.

scholarly journals Bioinformatics study on genes related to a high-risk postoperative recurrence of lung adenocarcinoma

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110180
Author(s):  
Xiao Lin ◽  
Meng Zhou ◽  
Zehong Xu ◽  
Yusheng Chen ◽  
Fan Lin
Keyword(s):  
Cell Cycle ◽  
Gene Ontology ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Candidate Genes ◽  
Postoperative Recurrence ◽  
High Expression ◽  
Ppi Network ◽  
Hub Genes ◽  
Expression Levels

In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein–protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease.

scholarly journals Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers

2021 ◽  
Vol 11 ◽  
Author(s):  
Sheng-Kai Liang ◽  
Li-Hsin Chien ◽  
Gee-Chen Chang ◽  
Ying-Huang Tsai ◽  
Wu-Chou Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pulmonary Tuberculosis ◽  
Lung Adenocarcinoma ◽  
Genome Wide Association Study ◽  
Lung Cancer Screening ◽  
Tuberculosis Infection ◽  
Eqtl Analysis ◽  
Nucleotide Polymorphisms ◽  
Programmed Death ◽  
Never Smokers

ObjectivesLung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women.Materials and MethodsDuring September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.ResultsA total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2.ConclusionsNovel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.

scholarly journals High expression levels of pyrimidine metabolic rate–limiting enzymes are adverse prognostic factors in lung adenocarcinoma: a study based on The Cancer Genome Atlas and Gene Expression Omnibus datasets

2020 ◽  
Vol 16 (3) ◽  
pp. 347-366 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Lung Cancer ◽  
Metabolic Rate ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Pyrimidine Metabolism ◽  
Expression Levels ◽  
Cancer Genome Atlas ◽  
Rate Limiting ◽  
Genome Atlas

Abstract Reprogramming of metabolism is described in many types of cancer and is associated with the clinical outcomes. However, the prognostic significance of pyrimidine metabolism signaling pathway in lung adenocarcinoma (LUAD) is unclear. Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, we found that the pyrimidine metabolism signaling pathway was significantly enriched in LUAD. Compared with normal lung tissues, the pyrimidine metabolic rate–limiting enzymes were highly expressed in lung tumor tissues. The high expression levels of pyrimidine metabolic–rate limiting enzymes were associated with unfavorable prognosis. However, purinergic receptors P2RX1, P2RX7, P2RY12, P2RY13, and P2RY14 were relatively downregulated in lung cancer tissues and were associated with favorable prognosis. Moreover, we found that hypo-DNA methylation, DNA amplification, and TP53 mutation were contributing to the high expression levels of pyrimidine metabolic rate–limiting enzymes in lung cancer cells. Furthermore, combined pyrimidine metabolic rate–limiting enzymes had significant prognostic effects in LUAD. Comprehensively, the pyrimidine metabolic rate–limiting enzymes were highly expressed in bladder cancer, breast cancer, colon cancer, liver cancer, and stomach cancer. And the high expression levels of pyrimidine metabolic rate–limiting enzymes were associated with unfavorable prognosis in liver cancer. Overall, our results suggested the mRNA levels of pyrimidine metabolic rate–limiting enzymes CAD, DTYMK, RRM1, RRM2, TK1, TYMS, UCK2, NR5C2, and TK2 were predictive of lung cancer as well as other cancers.

Aspirin use and mortality in men with localised prostate cancer: A cohort study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5084-5084
Author(s):  
Evelyn M Flahavan ◽  
Kathleen Bennett ◽  
Linda Sharp ◽  
Thomas Ian Barron
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Smoking Status ◽  
Tumour Size ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Specific Mortality ◽  
Prescription Refill ◽  
Cancer Specific Mortality ◽  
Cox 2

5084 Background: Cyclooxygenase-2 (COX-2) expression in prostate cancer has been associated with high grade tumours and poorer prognosis. Use of aspirin, a COX-2 inhibitor, has been associated with reduced prostate cancer mortality in some studies. These studies have not, however, provided information on the dose and timing of aspirin use. Methods: National Cancer Registry Ireland data was used to identify men with stage I-III prostate cancer (ICD10 C61) diagnosed 2001-2006. Aspirin use in the year preceding prostate cancer diagnosis was identified from linked prescription refill data (General Medical Services) and stratified by dose (low ≤75mg, high >75mg) and dosing intensity (proportion of days in that year with aspirin supply available). Cox proportional hazards models, adjusted for age, smoking status, year of incidence, comorbidity score, Gleason score, tumour size, pre-diagnostic statin use, and receipt of radiation (time varying) were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between aspirin use and all-cause and prostate cancer-specific mortality. Interactions with tumour characteristics were examined. Results: 2,936 men with stage I-III prostate cancer were identified (aspirin users, N=1,131; 38.5%). Median patient follow-up was 5.5 years. In multivariate analyses, aspirin use was not associated with a significant reduction in prostate cancer-specific (HR 0.90, 95% CI 0.68-1.20) or all-cause mortality (HR 0.98, 95% CI 0.84-1.15). In dose response analyses aspirin use was associated with a significantly lower risk of prostate cancer-specific mortality in men receiving >75mg of aspirin (HR 0.59, 95% CI 0.35-1.00, p=0.048) but not ≤75mg aspirin (HR 1.01, 95% CI 0.75-1.37, p=0.938). Stronger associations were also observed in men with higher aspirin dosing intensity or a Gleason score >7. Conclusions: Pre-diagnostic aspirin use, measured using objective prescription refill data, was associated with a significant reduction in prostate cancer-specific mortality in men with stage I-III prostate cancer receiving >75mg of aspirin. These results confirm previous findings, and provide important new information regarding the dose of aspirin associated with survival benefit.

Micro-RNA signature differences in lung adenocarcinoma with specific driver alterations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11066-11066
Author(s):  
Lorenza Landi ◽  
Pierluigi Gasparini ◽  
Stefania Carasi ◽  
Carmelo Tibaldi ◽  
Luciano Cascione ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Lung Tissue ◽  
Kras Mutation ◽  
Triple Negative ◽  
Egfr Mutation ◽  
Differential Expression Analysis ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Expression Levels

11066 Background: Oncogenic driving alterations define types of lung adenocarcinoma with different prognosis and sensitivity to targeted agents. MicroRNAs (miRNAs) are a new class of non-coding RNAs involved in gene expression regulation. How miRNAs are dysregulated in lung cancer with ALK translocation, EGFR or KRAS mutation is unknown. In this study we aimed to identify miRNA signatures according to the presence of specific driver and to correlate miRNAs deregulation with patient outcome. Methods: The study was conducted in a cohort of 70 lung cancer patients (pts) including 18 ALK+ tumors, 11 ALK-/EGFR mutation+, 15 ALK-/KRAS mutation+, 26 ALK-/EGFR and KRAS wild-type and defined as triple negative. Matched normal lung tissue from 18 cases representative of the entire cohort were also included onto the analysis. RNA was isolated from formalin-fixed paraffin-embedded tissue (FFPE), using the Recover ALL kit (Ambion). NanoString nCounter system platform was used to generate the miRNA profile. We used Limma to test for differential expression analysis of data. The miR-515 family expression between tissues was validated by RT-qPCRs, analyzed using the parametric t-test (unpaired, 2-tailed for validation). Results: miRNA expression profile clusters distinctly ALK+ pts from ALK- and normal lung tissue. Within the ALK- group we found specific miRNAs subsets able to sub-stratify KRAS versus EGFR careers clustering sharply triple negative versus EGFR mutation+ and triple negative versus KRAS mutation+. miRNAs belonging to the miR-515 family seems to be the most deregulated in the ALK+ versus ALK-. Although their expression is stably high in normal tissues and ALK+ class, they are highly downregulated in KRAS mutated versus EGFR mutated and versus triple negative (p-value <0.001 for all comparisons). Conclusions: miRNAs profile significantly differs in pts with ALK translocation, EGFR mutations and KRAS mutations. Analysis of miR-515 family members is ongoing in order to correlate their expression levels with pts’ outcome. In vitro modulation of miR-515 family expression levels, together with drugs treatment are ongoing in order to find possible chemo-resistance/chemo-sensitivity miRNA dependent, in ALK+ and ALK- model.

scholarly journals Mortality Risk factors and SOX2 and mTOR expression in Patients with Esophageal Cancer

2022 ◽  
Vol 67 (4) ◽  
pp. 346-357
Author(s):  
Gao Yu ◽  
Yang Yuexin ◽  
Lv Yin ◽  
Zhang Yiyin ◽  
Kang Mei ◽  
...  
Keyword(s):  
Risk Factors ◽  
Esophageal Cancer ◽  
Cardiovascular Mortality ◽  
Clinical Stage ◽  
Specific Protein ◽  
Expression Levels ◽  
Specific Mortality ◽  
Before And After ◽  
Cancer Specific Mortality ◽  
Distant Spread

Causes of mortality in EC patients are not confined to cancer-specific mortality but include various protein expressions of SOX2 and mTOR in Esophageal Cancer patients and their correlation with the clinical stage. Data about the risk factors and involvement of cancer-specific protein are still lacking. This study aimed to define the risk factors and association of SOX2 and mTOR expression in mortality in patients with EC. We conducted a retrospective cohort study to assess the risk factors for cancer-specific mortality and cardiovascular mortality in patients with esophageal cancer (EC). The expression rates of SOX2, as well as MTO, were checked in patients. The multivariate analysis revealed a high-risk EC mortality with age ≥ 65 years, black race, grade, stage, and sequence of treatment; radiation after surgery; radiation before and after surgery; Surgery both before and after radiation. While the cardiovascular mortality increased with age ≥ 65 years, adenocarcinoma type, grade, stage, and sequence of treatment. The expression rates of SOX2, as well as mTOR, were 75.5 percent and 86.8 percent in Esophageal Cancer, while were 10.7 percent and 7.5 percent in osteochondroma, respectively, which was statistically significant (P<0.05). Risk factors for cancer-specific mortality and cardiovascular mortality in EC patients include older age at diagnosis, male sex, non-married status, grade III of the tumor, the regional or distant spread of the tumor, no cancer-directed therapy. The expression levels of SOX2, mTOR, and the total survival time were related to the different stages. It shows an upward trend for the expression levels of mTOR and SOX2 in Esophageal Cancer tissues. The expression levels of SOX2 and mTOR are related to the clinical stage, metastasis, and prognosis.

scholarly journals High expression of PD-L1 Predicts Worse Overall Survival in the Cavitary Lung Adenocarcinoma

2020 ◽  
Author(s):  
Jiangyong Liu ◽  
Mingming Gu ◽  
Yang Xue ◽  
Yong Ren ◽  
Wencai Huang
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Good Prognosis ◽  
High Expression ◽  
Quantitative Immunofluorescence ◽  
L1 Protein ◽  
Infiltrating Lymphocytes

Abstract Objective Solitary cavitary lung cancer is one of the rare types of lung cancer. Generally, the relationship between cavitary lung adenocarcinoma and immunotherapy remains unknown. We aimed to assess programmed cell death ligand-1(PD-L1) expression and CD8-positive (CD8+) tumor infiltrating lymphocytes (TILs) density, and evaluate their prognostic significance of patients with cavitary lung adenocarcinoma (LUAD). Methods 65 patients diagnosed as solitary cavitary LUAD were included in this study, 30 cases of noncavitary LUAD patients were collected as controls, and their specimens from surgery or biopsy were obtained. Expression of PD-L1 protein and CD8+ TILs were detected by traditional immunohistochemistry and multiplex quantitative immunofluorescence technology. The correlations of PD-L1 expression and clinicopathological features, including overall survival in cavitary LUAD patients was evaluated based on the follow-up data. Results Overexpression of PD-L1 protein was detected in the tumor tissues of cavitary LUAD patients compared to the noncavitary LUAD controls. PD-L1 expression level was significantly related to the lymph node (P = 0.001), TNM stage (P = 0.024), and CD8+ TIL status (rs= -0.272, P = 0.025). High PD-L1 expression predicted high mortality rate (P < 0.001), but CD8+ TIL group showed better survival in cavitary LUAD patients (P = 0.011). This phenotype with high PD-L1 expression and low CD8 + TIL predicted poorer overall survival of the patients with cavitary LUAD, compared to the other phenotypes. Moreover, CD8+ TIL was an independent good prognosis factor. Conclusion We firstly demonstrated that PD-L1 is upregulated in the cavitary LUAD patients, and high expression of PD-L1 negatively correlated with CD8 T cell infiltrating status. High PD-L1 expression and low CD8 + TIL can predict poorer overall survival of the patients with cavitary LUAD.

scholarly journals Role of high expression levels of STK39 in the growth, migration and invasion of non-small cell type lung cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (38) ◽  
pp. 61366-61377 ◽  
Author(s):  
Zhao Li ◽  
Wenzhuo Zhu ◽  
Liwen Xiong ◽  
Xiaobo Yu ◽  
Xi Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Small Cell ◽  
High Expression ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cell Type ◽  
Expression Levels

Mediastinal lymph node examination and survival in resected early-stage non-small cell lung cancer in the Surveillance, Epidemiology, and End Results (SEER) database.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7069-7069
Author(s):  
Raymond U Osarogiagbon ◽  
Xinhua Yu
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Mediastinal Lymph Node ◽  
Small Cell ◽  
Small Cell Lung ◽  
Term Survival ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Cancer Specific Mortality

7069 Background: Pathologic nodal stage is a key prognostic factor in resectable non-small cell lung cancer (NSCLC). Mediastinal lymph node (MLN) metastasis connotes a poor prognosis. Yet, some NSCLC resections in the US do not include MLN examination. Methods: We analyzed SEER data from 1998 to 2002 to quantify the long-term survival impact of failure to examine MLN in resected NSCLC. We used Kaplan-Meier methods to compare the unadjusted survival difference between patients with, and without, MLN examination. We used Cox proportional hazards and competing risk models to serially adjust for the impact of risk factors on survival differences. Results: Sixty-two percent of patients with pathologic N0 or N1 NSCLC had no MLN examined. Men, African-Americans, patients with more advanced stage, and those who had less than pneumonectomy were less likely to have MLN examination. Five-year all-cause mortality (46.9% v 51.7%, p<.001), and lung cancer-specific mortality (31.5% v 36%, p<.001), rates were higher in those without MLN examination. After adjustment for potential confounders, MLN examination was associated with a 6% reduction in all-cause mortality (HR, 0.94; CI, 0.89-0.99; p=.014), and 10% reduction in lung cancer-specific mortality (HR, 0.90; 95% CI, 0.84-0.96; p=.002) rates. The excess risk in 1 year’s cohort of U.S. lung resections was 2,700 lives over 5 years. Conclusions: Failure to examine MLN was a common practice in "MLN-negative" NSCLC resections, which significantly impaired long-term survival. Efforts to understand the etiology of this quality gap, and measures to eliminate it, are warranted.

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