scholarly journals Pathological and Prognostic Indications of the mdig Gene in Human Lung Cancer

2021 ◽  
Vol 55 (S2) ◽  
pp. 13-28
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Human Lung Cancer ◽  
Clinical Samples ◽  
Lung Carcinogenesis ◽  
Expression Status

Background/Aims: The mineral-dust-induced gene mdig is a lung-cancer-associated oncogene. The focus of this study is to evaluate the expression status of mdig in lung cancer and to assess its influence in predicting the patient’s overall survival. Methods: Using high-density tissue microarrays and clinical samples of synchronous multiple primary lung cancer (SMPLC), we investigated the expression of mdig through immunohistochemistry and utilized the open-access lung cancer patient databases containing genomic and transcriptomic data from the UCSC Xena and TCGA web platforms to determine the prognostic values of mdig expression status among different subtypes of lung cancer. Results: mdig is upregulated in smokers and in lung squamous cell carcinoma. High mdig expression predicted poor overall survival in lung squamous cell carcinoma and female smokers. Among tumor tissues from SMPLC patients, we not only unraveled the highest positive rate of mdig expression, but also revealed a unique cytoplasmic, rather than nuclear localization of mdig protein. Furthermore, by inspecting some pathological but not cancerous lung tissues, we believe that mdig is required for the transformation of non-cancerous lung cells to the fully-fledged cancer cells. Conclusion: These data suggested that mdig is involved in various stages of lung carcinogenesis, possibly through the epigenetic regulation on some critical cancer-associated genes, and increased mdig expression is an important prognostic factor for some types of lung cancer.

scholarly journals Interaction between the microbiome and TP53 in human lung cancer

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
K. Leigh Greathouse ◽  
James R. White ◽  
Ashely J. Vargas ◽  
Valery V. Bliskovsky ◽  
Jessica A. Beck ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cigarette Smoke ◽  
Squamous Cell ◽  
Human Lung Cancer ◽  
Normal Lung ◽  
Lung Carcinogenesis ◽  
Bacterial Gene ◽  
Tp53 Mutations

Abstract Background Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort. Results Overall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas. Conclusions The results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection.

scholarly journals Development and validation of an individualized immune prognostic model in stage I–III lung squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qi-Fan Yang ◽  
Di Wu ◽  
Jian Wang ◽  
Li Ba ◽  
Chen Tian ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Model ◽  
Lung Squamous Cell Carcinoma ◽  
Risk Groups ◽  
Stage I ◽  
Tissue Samples ◽  
Mutation Burden

AbstractLung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.

scholarly journals UBE2D1 RNA Expression Was an Independent Unfavorable Prognostic Indicator in Lung Adenocarcinoma, but Not in Lung Squamous Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Data ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Rna Expression

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.

scholarly journals Overall survival of patients with non-small cell lung cancer after surgery treatment

2018 ◽  
Vol 75 (12) ◽  
pp. 1157-1164
Author(s):  
Olivera Loncarevic ◽  
Slobodan Acimovic ◽  
Jelena Vukovic ◽  
Marko Stojisavljevic ◽  
Nebojsa Maric ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Small Cell ◽  
The Other ◽  
Small Cell Lung ◽  
Cumulative Survival ◽  
Recurrence Group

Background/Aim. Lung cancer is one of the most common malignant tumors. About 80% of all lung cancers are non-small cell lung cancer (NSCLC). According to histopathological characteristics, the most common types of NSCLC are squamous cell carcinoma and adenocarcinoma. The aim of this study was to evaluate the overall survival rate in the NSCLC patients initially received surgery according to its histopathological type and T ? primary tumor, N ?regional lymph nodes, M ? distant metastasis (TNM) stages which were treated with surgical treatment, and after that, according to the TNM stage, chemotherapy protocols and/or radiation therapy. Methods. This retrospective case series study included all patients with NSCLC admitted to the Military Medical Academy in Belgrade in the period 2010?2015. A total number of selected patients was 85 (27 females and 58 males). Results. Out of 41 patients with squamous cell carcinoma, 19.5% deceased. On the other hand, in the group of patients with adenocarcinoma, 43.2% out of 44 patients deceased. The average cumulative survival was statistically significantly lower in the adenocarcinoma patients in comparison to the patients with squamous cell carcinoma (1,605.2 vs.1,304.8 days; p = 0.005). On the other hand, the average cumulative survival was statistically significantly lower in our patients in the recurrence group with adenocarcinoma in comparison to the recurrence group with squamous cell carcinoma (1,212.8 vs. 1,835.5 days; p = 0.032). Conclusion. Adenocarcinoma is more aggressive cancer in comparing to squamous cell carcinoma with lower overall survival in comparing to squamous cell carcinoma. Additional studies are needed to identify risk factors for recurrence after surgery, and to additionally explain role of tumor markers and molecular biological techniques in the progression of this kind of cancer.

scholarly journals Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2071 ◽  
Author(s):  
Patricia P. Reis ◽  
Sandra A. Drigo ◽  
Robson F. Carvalho ◽  
Rainer Marco Lopez Lapa ◽  
Tainara F. Felix ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Genes ◽  
Lung Squamous Cell Carcinoma ◽  
High Specificity ◽  
Mirna Signature ◽  
Lung Tumorigenesis ◽  
Lung Cancer Patients

Background: Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules, and detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection. We aimed to identify circulating miRNA signatures in plasma from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and to verify whether miRNAs regulate lung oncogenesis pathways. Methods: RNA isolated from 139 plasma samples (40 LUAD, 38 LUSC; 61 healthy/non-diseased individuals) were divided into discovery (38 patients; 21 controls for expression quantification using an 800-miRNA panel; Nanostring nCounter®) and validation (40 patients; 40 controls; TaqMan® RT-qPCR) cohorts. Elastic net, Maximizing-R-Square Analysis (MARSA), and C-Statistics were applied for miRNA signature identification. Results: When compared to healthy individuals, 580 of 606 deregulated miRNAs in LUAD and 221 of 226 deregulated miRNAs in LUSC had significantly increased levels. Among the 10 most significantly overexpressed miRNAs, 6 were common to patients with LUAD and LUSC. Further analysis identified three signatures composed of 12 miRNAs. Signatures included miRNAs commonly overexpressed in patient plasma. Enriched pathways included target genes modulated by three miRNAs in the C-Statistics signature: miR-16-5p, miR-92a-3p, and miR-451a. Conclusions: The 3-miRNA signature (miR-16-5p, miR-92a-3p, miR-451a) had high specificity (100%) and sensitivity (84%) to predict cancer (LUAD and LUSC). These miRNAs are predicted to modulate genes and pathways with known roles in lung tumorigenesis, including EGFR, K-RAS, and PI3K/AKT signaling, suggesting that the 3-miRNA signature is biologically relevant in adenocarcinoma and squamous cell carcinoma of the lung.

scholarly journals Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 477 ◽  
Author(s):  
Yu Zhou ◽  
Qi Zhang ◽  
Meijun Du ◽  
Donghai Xiong ◽  
Yian Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Lung Squamous Cell Carcinoma ◽  
P Values ◽  
Chemopreventive Agent ◽  
Exosomal Mirnas ◽  
Pharmacodynamic Biomarkers

Background: Chemopreventive agent (CPA) treatment is one of the main preventive options for lung cancer. However, few studies have been done on pharmacodynamic biomarkers of known CPAs for lung cancer. Materials and methods: In this study, we treated mouse models of lung squamous cell carcinoma with three different CPAs (MEK inhibitor: AZD6244, PI-3K inhibitor: XL-147 and glucocorticoid: Budesonide) and examined circulating exosomal miRNAs in the plasma of each mouse before and after treatment. Results: Compared to baselines, we found differentially expressed exosomal miRNAs after AZD6244 treatment (n = 8, FDR < 0.05; n = 55, raw p-values < 0.05), after XL-147 treatment (n = 4, FDR < 0.05; n = 26, raw p-values < 0.05) and after Budesonide treatment (n = 1, FDR < 0.05; n = 36, raw p-values < 0.05). In co-expression analysis, we found that modules of exosomal miRNAs reacted to CPA treatments differently. By variable selection, we identified 11, 9 and nine exosomal miRNAs as predictors for AZD6244, XL-147 and Budesonide treatment, respectively. Integrating all the results, we highlighted 4 miRNAs (mmu-miR-215-5p, mmu-miR-204-5p, mmu-miR-708-3p and mmu-miR-1298-5p) as the key for AZD6244 treatment, mmu-miR-23a-3p as key for XL-147 treatment, and mmu-miR-125a-5p and mmu-miR-16-5p as key for Budesonide treatment. Conclusions: This is the first study to use circulating exosomal miRNAs as pharmacodynamic biomarkers for CPA treatment in lung cancer.

The Overall Survival of Non-Small Cell Lung Cancer Patients Group pN2 after Radical Surgery and Postoperative Radiotherapy

2020 ◽  
Vol 65 (1) ◽  
pp. 42-47
Author(s):  
V. Sotnikov ◽  
G. Panshin ◽  
V. Solodkiy ◽  
V. Chkhikvadze ◽  
V. Kharchenko ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Postoperative Radiotherapy ◽  
Small Cell ◽  
Small Cell Lung

Purpose: Comparative analysis of the overall survival (OS) in different subgroups of the patients with non-small cell lung cancer (NSCLC) with affected mediastinal lymph nodes (pN2) after surgical and combined treatment using postoperative radiotherapy (PORT). Material and methods: A comparative assessment of the overall survival of 243 patients with NSCLC stages IIIA, IIIB (pT1–4N2M0) was carried out: the I group – 79 patients after radical (R0) surgical treatment (lobe/bilobectomy, pulmonectomy with ipsilateral mediastinal lymph node dissection) and the second group – 164 patients after the combined modality therapy with the same volume of surgery and postoperative radiotherapy in the mode of hypofractionation (daily dose 3 Gy, 5 times a week, TD = 36–39 Gy (EQD2 = 43.2–46.8 Gy, α/β = 3) or classical fractionation (2 Gy, 5 times a week, TD = 44 Gy). We analyzed subgroups of men and women, patients younger than 60 years and older, with central and peripheral cancer, squamous cell carcinoma and adenocarcinoma, with different gradation of tumors according to the criterion T (pT1–4). Results: In the compared groups, 2-year and 5-year OS was significantly higher in the PORT group (62.4 and 31.6 vs 44.8 % and 12.3 %, p = 0.0028), at the expense of male patients (62.4 and 31.6 % vs 44.8 and 12.3 %, p = 0.0028), patients with central cancer (59.2 and 43.7 % vs 36.3 % and n/a, p = 0.0023), patients with squamous cell carcinoma (64.0 % and 43.1 % vs 42.3 % and 6.7 %, p = 0.0006), patients older than 60 years (74.8 and 46.2 % vs 45.1 % and n/a, p = 0.007). A more detailed analysis revealed that PORT significantly increased 2- and 5-year OS in the central squamous cell carcinoma of the lung (67.3 and 53.0 % vs. 33.3 and 0 %, respectively, p = 0.0013), and in pT3–4 tumors (2-year OS 57.1 vs. 36.4 %, respectively, p = 0.0102). There was only a tendency of increasing OS after the PORT in T2 tumors (5-year OS 31.1 vs 15.4 %, respectively, p = 0.1319). In T1 tumors, no differences in OS were found, possibly due to the small number of cases (27). In peripheral squamous cell carcinoma there was a statistically insignificant increasing of 5-year OS – 7 %. There was no significant differences in OS survival were obtained in central and peripheral lung adenocarcinoma between the I and II groups. Conclusion: In the patients with non-small cell lung cancer pN2, radically operated (R0) in the volume of lobe/bilobectomy, pulmonectomy with ipsilateral mediastinal lymph node dissection, PORT can be recommended for central squamous cell carcinoma pT1–4. In the patients with peripheral squamous cell carcinoma, PORT can be discussed for the patients with individually assessed high risk of the locoregional relapse. PORT, within the scope of irradiation and total doses used in this study, has no age restrictions. The feasibility of PORT for radically operated patients with pN2 lung adenocarcinoma requires further study.

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