scholarly journals BSCI-09. Multiomic single cell analysis reveals emerging principles of tumor immune microenvironment inherent to NSCLC brain metastases

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii3-iii3
Author(s):  
Lei Wen ◽  
Changguo Shan ◽  
Da Liu ◽  
Cheng Zhou ◽  
Linbo Cai
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Single Cell ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Immune Microenvironment ◽  
Lung Cancer Patients ◽  
Tumor Immune Microenvironment ◽  
Treatment Naïve

Abstract Brain is one of the most common sites for distant metastasis of lung cancer. Treatment naïve lung cancer patients diagnosed with brain metastasis are left with very limited options. Checkpoint inhibition is a powerful immunotherapy strategy but delivers benefit only to a small population of patients. Here we harnessed the power and resolution of single cell RNA sequencing and single cell TCR/BCR sequencing to investigate the tumor immune microenvironment (TIME) of NSCLC brain metastases. We enrolled treatment naïve lung cancer patients with brain metastasis. The enrolled subjects covered different histology types and driver gene mutation status. We revealed the emerging principles of innate and adaptive immune components inherent to NSCLC brain metastases. We also uncovered several significant intercellular communication patterns that potentiates cancer cell seeding and fosters cancer cell proliferation. Those results served as a starting point to design optimal immunotherapy strategies for advanced lung cancer patients with limited options.

Brain metastasis in lung cancer: Are there any predictive risk factors?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21740-e21740
Author(s):  
Salma Ait Batahar
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Control Group ◽  
Lung Cancer Patients ◽  
Poorly Differentiated Carcinoma ◽  
Poorly Differentiated ◽  
The Mean ◽  
The Moment

e21740 Background: Lung cancer is the first cause of death by cancer worldwide. Brain metastases in lung cancer are associated to an even poorer prognosis of this cancer. Identifying patients with a higher risk of developing brain cancer may help their prognosis by including systematic brain radiotherapy to their treatment. But what are risk factors of brain metastasis occurrence in lung cancer patients? Methods: To answer this question, we conducted a case control study comparing two groups of lung cancer patients. The cases group included 35 lung cancer patients with brain metastasis at the moment of diagnosis while the control group was made of 49 lung cancer patient with no brain metastasis at the moment of diagnosis. Many parameters were compared between the two groups such as: professional exposure, type and duration of smoking, medical history, clinical and radiological presentation as well as the histological type of the carcinoma. Results: The mean age was 56 for the cases group and 61 for the control group. Nonsmokers represented 14% in the cases group and 4% in the control group. The average smoking was 34 pack-year for the cases group and 31 pack-year for the control group and in both groups 51% of patients smoked a mixture of tobacco and Cannabis. 36% of the control group patients had an exposure to a professional carcinogen while 48% of the cases group patients had one. Digital clubbing was found in 62% of cases group patients and in 51% of the control group patients. 17% of the cases group patients had two more metastases outside the lungs and other than the brain ones while this rate was only 6% for the control group patients. The mean level of LDH (Lactate Dehydrogenase) was 340 U/L for the cases group and 342 U/L for the control group while the CRP (C- reactive protein) one was 78 mg/L for the cases group and 59 mg/L for the control group. The main histological type found in both groups was Adenocarcinoma (25% in the cases group and 18% in the control group) followed by the poorly differentiated carcinoma in the cases group and the squamous cell carcinoma in the control group. Small cell carcinoma was found in 5% of the patients with brain metastases and in 8% of the patients without brain metastases. Conclusions: Patients with brain metastases have a higher professional carcinogens exposure, a higher percentage of nonsmokers, more digital clubbing, and higher CRP levels than patients with no brain metastases. They also have more than one metastasis at the moment of the diagnosis and the predominant histological types are Adenocarcinoma and poorly differentiated carcinoma.

scholarly journals The Dual Effect of CD28 on The Prognosis of Lung Cancer Based On Nomograms: A Comprehensive Analysis of The Tumor Immune Microenvironment

2020 ◽  
Author(s):  
dantong sun ◽  
Lu Tian ◽  
Tiantian Bian ◽  
Han Zhao ◽  
Junyan Tao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Multivariate Analyses ◽  
Cancer Prognosis ◽  
Immune Microenvironment ◽  
Dual Effect ◽  
Internal Validation ◽  
Lung Cancer Patients ◽  
Tumor Immune Microenvironment

Abstract Background Lung cancer has ranked first in China in recent years, and TIME-related molecules may serve as biomarkers for the prognosis of lung cancer. Nomograms are widely used tools for the evaluation of prognosis in malignancies. We performed this study to construct nomograms based on TIME for predicting the prognosis of lung cancer. Methods Univariate and multivariate analyses were performed to estimate prognosis. TIME-related variables and basic clinical characteristics were included in the nomograms. Discrimination and calibration were used for the internal validation of the nomograms. Patients in our center and in the TCGA database were involved in the construction of the nomograms. Results Both LUAD and lung cancer patients with a higher expression of CD28 had a shorter DFS (P = 0.0011; P = 0.0001) but a longer OS (P = 0.0001; P = 0.0282). Nomograms for the DFS of young LUAD patients and the OS of LUAD and lung cancer patients were constructed. The established nomograms provide an easy way to estimate prognosis. Patients may obtain not only probabilities for disease progression and 1-year, 3-year or 5-year survival but also a precise and individualized follow-up regimen. Conclusion TIME-related variables are closely associated with the prognosis of lung cancer patients, especially young LUAD patients. CD28, which has a dual effect on lung cancer prognosis, may be a novel biomarker for not only the prognosis of lung cancer but also sensitivity to immunotherapy. Nomograms based on TIME may be a novel way to predict the prognosis of lung cancer.

scholarly journals Neurofilament Light Chain as A Biomarker for Brain Metastases

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2852 ◽  
Author(s):  
Anne Winther-Larsen ◽  
Claus Vinter Bødker Hviid ◽  
Peter Meldgaard ◽  
Boe Sandahl Sorensen ◽  
Birgitte Sandfeld-Paulsen
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Single Molecule ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Lung Cancer Patients ◽  
Potential Biomarker

Background: Brain metastases are feared complications in cancer. Treatment by neurosurgical resection and stereotactic radiosurgery are only available when metastatic lesions are limited and early detection is warranted. The neurofilament light chain (NfL) is a sensitive neuron-specific biomarker released following neuronal decay. We explored serum NfL as a biomarker of brain metastases. Methods: Serum was collected from 43 stage IV lung cancer patients with brain metastases and 25 stage I lung cancer patients. Serum was collected at time of cancer diagnosis and at time of brain metastasis diagnosis. In nine patients with brain metastases, additional samples were available between the two time points. NfL was quantified by Single Molecule Array (Simoa)™. Results: The median NfL level was significantly higher in patients with brain metastases than in patients without (35 versus 16 pg/mL, p = 0.001) and separated patients with an area under the curve of 0.77 (0.66–0.89). An increase in NfL could be measured median 3 months (range: 1–5) before the brain metastasis diagnosis. Further, a high level of NfL at time of brain metastasis diagnosis correlated with an inferior survival (hazard ratio: 2.10 (95% confidence interval: 1.11–3.98)). Conclusions: This study implies that NfL could be a potential biomarker of brain metastases.

scholarly journals Brain Metastases in Lung Cancer Patients: Clinical Potential Risk Factors of CYFRA21-1 and CEA

2021 ◽  
Author(s):  
Jing Tang ◽  
Tie Sun ◽  
Qian-Min Ge ◽  
Rong-Bin Liang ◽  
Ting Su ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Binary Logistic Regression ◽  
Binary Logistic Regression Analysis ◽  
Lung Cancer Patients

Abstract Background At present, little is known about the specific risk factors of brain metastasis in patients with lung cancer. This study aims to explore the risk factors of brain metastasis. Methods From April 1999 to July 2017, a total of 1,615 lung cancer patients were included in this retrospective study. The patients were divided into two groups, namely brain metastasis group and non-brain metastasis group. Student's t test, non-parametric rank sum test and chi-square test were used to describe whether there is a significant difference between the two groups. We compared the serum biomarkers of the two groups of patients, including alkaline phosphatase (ALP), Calcium, calcium hemoglobin (HB), alpha fetoprotein (AFP), cancer embryonic antigen (CEA), CA-125, CA-199, CA- 153, CA-724, cytokeratin fragment 19 (CYFRA 21 − 1), total prostate specific antigen (TPSA), squamous cell carcinoma antigen (SCC-Ag) ,and neuron specific enolase (NSE). Binary logistic regression analysis was used to determine its risk factors, and receiver operating curve (ROC) analysis was used to evaluate its diagnostic value for brain metastases in patients with lung cancer. Results In the analysis of brain metastases in patients with lung cancer, binary logistic regression analysis showed that CYFRA21-1 and CEA are independent risk factors for brain metastases in patients with lung cancer (both P < 0.001). The sensitivity and specificity of diagnosing brain metastasis were CYFRA21-1, 38.0% and 87.4%, respectively; CEA was 39.7% and 79.3%, respectively. Conclusion Serum CYFRA21-1 and CEA have predictive value in the diagnosis of brain metastases in patients with lung cancer.

Brain metastasis in a series of NSCLC: Egyptian experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18001-e18001
Author(s):  
Salah Eldeen Elmesidy ◽  
Mahmoud Abdelsalam ◽  
Husam Zawam
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Developing Brain ◽  
Smoking History ◽  
Lung Cancer Patients ◽  
Significant Difference

e18001 Background: Incidence of cerebral metastasis is increasing among lung cancer patients. Many factors have been reported associated with increase risk of brain metastasis. The aim of this retrospective analysis is to investigate the predictive factors for the development of brain metastasis in lung cancer patients. Methods: We retrospectively analyzed histologically proven lung cancer patients radiologically diagnosed of having brain metastases who presented to Kasr Al-Eini Center for Oncology (NEMROCK) in the period from 2004 till 2010, with follow up period of 6 months at least. The following factors were analyzed: age, gender, PS, smoking history, tumor size & grade preceding development of brain metastasis. Results: Our study included 403 patients. 67 patients (16.6%) experienced brain metastasis during the course of their disease. 40 (10%) patients had brain metastasis among other sites of distant spread at first presentation which represent 88.9% of patients presented with metastatic disease. In a median follow-up of 17.1 months (6-77) the time to develop brain metastasis (TTBM) for the whole group was 5 months (range 2-22 months) (95% CI : 4.3-7.7). The most important factor affecting the TTBM was the use of chemotherapy before developing brain metastasis with a median TTBM of 5.9 months (95%CI : 3.2-6.8) among those who received chemotherapy compared to 2 months among the patients who didn't receive chemotherapy (P= <0.0001). The second factor was PS at time of initial diagnosis (P= 0.027). The median OS after brain metastasis was 6 months (95% CI : 4.26-7.74). On univariate analysis, PS and use of chemotherapy after developing brain metastases showed statistically significant difference affecting OS. Conclusions: We concluded that PS as well as use of chemotherapy are the 2 main factors associated with shorter time to develop brain metastasis. PS and use of chemotherapy after developing brain metastases showed longer OS after developing brain metastases. Keywords: NSCLC, Brain metastasis, Egypt

scholarly journals BSCI-12. COMPREHENSIVE GENOMIC ANALYSIS OF BRAIN METASTASES FROM MULTIPLE CANCER TYPES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i3-i3
Author(s):  
Kazutaka Fukumura ◽  
Xizeng Mao ◽  
Xingzhi Song ◽  
Grant Fischer ◽  
Jie Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Genomic Analysis ◽  
Primary Tumors ◽  
Lung Cancer Patients ◽  
Cancer Types ◽  
Methylation Profiling

Abstract PURPOSE: Brain metastases occur in approximately 8–10% of patients with cancer, and the incidence has increased over the past decades. The most common primary tumors responsible for brain metastases are lung cancer, melanoma, renal cell carcinoma (RCC), breast cancer and colorectal cancer. The precise mechanisms by which genomic and transcriptional abnormalities drive the formation of brain metastases remain unclear. Here, we conducted comprehensive genomic and transcriptional analysis with paired primary tumor tissue (or extracranial metastasis tissue) and brain metastasis tissue using whole-exome sequencing (WES), mRNA-Seq and global methylation profiling. METHODS: Frozen, paired brain metastasis tissue and primary tumor tissue (or extracranial metastasis tissue) and white blood cells were acquired from RCC (n=12), breast cancer (n=17), lung cancer (n=15) and melanoma (n=14) patients, followed by extraction of DNA and RNA. WES and mRNA-Seq were performed on the Illumina HiSeq4000 platform. For methylation profiling, DNA was analyzed using Illumina Infinium MethylationEPIC Beadchip arrays. RESULTS: Somatic mutations or methylation of VHL gene were identified in 81.8% of RCC patients. Gene Set Enrichment Analysis revealed significant enrichment for hypoxia pathway transcripts in RCC brain metastases relative to primary tumors. The most common alterations in breast and lung cancer patients were TP53 mutations with frequencies of 50.0% and 73.3%, followed by ERBB2 alterations (43.8%) in breast cancer patients and mutually exclusive alterations of EGFR (33.3%) and KRAS (26.7%) in lung cancer patients. Mutually exclusive alterations of NRAS (42.9%) and BRAF (42.9%) were also observed in melanoma patients. Gene expression and epigenetic analysis revealed characteristics of brain metastases depending on primary cancer types. CONCLUSIONS: Comprehensive genomic analysis of brain metastases from four different cancer types revealed that brain metastasis tissues have unique genomic, transcriptional and epigenetic profiles according to histopathology groups. Therefore, the therapeutic strategies should be designed based at least in part on tumor histiogenesis.

scholarly journals Single-Cell Expression Landscape of SARS-CoV-2 Receptor ACE2 and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1250
Author(s):  
Guangchun Han ◽  
Ansam Sinjab ◽  
Kieko Hara ◽  
Warapen Treekitkarnmongkol ◽  
Patrick Brennan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Cell ◽  
Cancer Patients ◽  
Expression Profiles ◽  
Lung Cells ◽  
Alveolar Type ◽  
Specific Expression ◽  
Lung Cancer Patients ◽  
Normal Tissues ◽  
Cell Expression

The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of ACE2 and SARS-CoV-2-priming proteases TMPRSS2 and TMPRSS4 in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of ACE2, TMPRSS2, and TMPRSS4. Analysis of 70,030 LUAD- and normal-derived epithelial cells showed that ACE2 levels were highest in normal alveolar type 2 (AT2) cells and that TMPRSS2 was expressed in 65% of normal AT2 cells. Conversely, the expression of TMPRSS4 was highest and most frequently detected (75%) in lung cells with malignant features. ACE2-positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated HHIP, and the scavengers CD36 and DMBT1. Notably, the viral scavenger DMBT1 was significantly positively correlated with ACE2 expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.

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