PD-1 and PD-L1 Related Comprehensive Analysis of Lung Squamous Cell Carcinoma

Aims : The present study explored the clinical significance of microRNA-22 (miR-22) expression in lung squamous cell carcinoma and to explore the targeting relationship with vascular endothelial growth factor receptor 3 (VEGFR3). Methods: A total of 49 patients with lung squamous cell carcinoma who underwent surgical treatment was selected. The expression of miR-22 was detected by fluorescence quantitative real-time PCR (qPCR), the expression of VEGFR3 was detected by Western blotting assays, and D240 labeled microlymphatic vessels density (MLVD) was detected immunohistochemistry (IHC). Lung squamous cell carcinoma cell line SK-MES-1 was selected and the targeting relationship between miR-22 and VEGFR3 was analyzed by double luciferase reporter gene assay. Western blotting assays were used to detect the expression of vascular endothelial growth factor-D (VEGF-D) and D240 in the blank control group, empty vector transfection group, miR-22 transfection group, miR-22 and VEGFR3 co-transfection group. Results: The expression range of miR-22 in lung squamous cell carcinoma was 0.8-3.5. The expression of miR-22 in lung squamous cell carcinoma was significantly different by tumor maximum diameter, lymph node metastasis, vascular invasion and TNM stage. The expression of miR-22 was linked to survival time. There was a negative correlation between miR-22 and VEGFR3, miR-22 and MLVD. Double luciferase reporter gene assays showed that miR-22 reduced the luciferase activity of pGL3-VEGFR3-WT transfected cells. Compared with the control group, the expression of VEGF-D and D2-40 in the miR-22 transfection group was significantly decreased. However, VEGF-D and D240 in the miR-22 and VEGFR3 cotransfection group reversed the changes. Conclusion: We assumed that the abnormal expression of miR-22 in lung squamous cell carcinoma may be involved in the development and progression of lung squamous cell carcinoma. MiR-22 negatively regulated the target gene VEGFR3 to mediate lymphangiogenesis. The expression of miR-22 may also be linked to the prognosis of the disease.

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Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents

Oncotarget ◽

10.18632/oncotarget.13806 ◽

2016 ◽

Vol 8 (12) ◽

pp. 18885-18900 ◽

Cited By ~ 12

Author(s):

Donghai Xiong ◽

Jing Pan ◽

Qi Zhang ◽

Eva Szabo ◽

Mark Steven Miller ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lung Squamous Cell Carcinoma ◽

Mouse Lung ◽

Chemopreventive Agents ◽

Gene Expression Signatures

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

Scientific Reports ◽

10.1038/s41598-021-92115-0 ◽

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.

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A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma

BMC Cancer ◽

10.1186/s12885-021-08360-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Guichuan Huang ◽

Jing Zhang ◽

Ling Gong ◽

Yi Huang ◽

Daishun Liu

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Risk Score ◽

Squamous Cell ◽

Cox Regression ◽

Lung Squamous Cell Carcinoma ◽

Gene Signature ◽

Gene Set Enrichment Analysis ◽

Related Gene ◽

Cox Regression Analysis

Abstract Background Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. Methods The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. Results Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. Conclusion A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.

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The Current Landscape of Immune Checkpoint Blockade in Metastatic Lung Squamous Cell Carcinoma

Molecules ◽

10.3390/molecules26051392 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1392

Author(s):

Hong Yuan ◽

Jing Liu ◽

Jun Zhang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Immune Checkpoint ◽

Unmet Need ◽

Lung Squamous Cell Carcinoma ◽

Standard Of Care ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Programmed Death

In addition to surgery, chemotherapy, radiotherapy, and targeted therapy, immunotherapy has emerged as a standard pillar of cancer treatment. Immune checkpoint inhibitors (ICIs) such as targeting programmed death-1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have been integrated into standard-of-care regimens for patients with advanced lung squamous cell carcinoma (LUSC), who were previously limited by the lack of treatment options. Atezolizumab, durvalumab, nivolumab, and pembrolizumab are all currently used as part of standard-of-care treatment for different stages of lung cancer. Recent successes and failures of immune checkpoint blockade-based combination therapies have provided significant insights into implementing combination strategies in LUSC. Therefore, there is an urgent need to correctly select patients who are more likely to respond to immunotherapy and understand the mechanisms of primary or acquired resistance. In this review, we aim at summarizing the emerging clinical data on the promise and challenge of ICIs, discussing the unmet need of potential biomarkers for predicting response or resistance to immunotherapy, and providing an overview of the current immune landscape and future directions in advanced LUSC.

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