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2021 ◽  
Ziyang Zhu ◽  
Fajiu Li ◽  
Xiaojiang Wang ◽  
Chenghong Li ◽  
Qinghua Meng ◽  

Background: The study aims to use noninvasive transrenal DNA in advanced non-small-cell lung cancer (NSCLC) patients for treatment monitoring and prognosis. Methods: Urine specimens were collected longitudinally for 103 late-stage NSCLC patients. Detection of targetable mutations in transrenal DNA was achieved by digital droplet PCR. Patients' overall survival outcomes were correlated with levels of transrenal DNA. Results: Corresponding patients' matched tumor results demonstrated concordance rate of 95.6% with transrenal DNA. A significant decline in levels was observed after treatment initiation. We observed changes in transrenal DNA levels to be significantly associated with survival for patients (p < 0.0001). Conclusion: Our results demonstrated strong predictive values of transrenal DNA to better identify patients with poorer survival outcomes and may further complement disease management.

2021 ◽  
Jia-Hao Jiang ◽  
Chang-Yue Chen ◽  
Jian Gao ◽  
Jing Li ◽  
Yuan Lu ◽  

Abstract Backgrounds: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) holds great promise for improving pathological diagnosis and selecting treatment in non-small cell lung cancer (NSCLC). In addition, previous studies have shown that DNA methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. Methods: we first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus and further identified the results by performing whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. Results: the bioinformatic analysis revealed that an NSCLC-specific DNA methylation marker panel which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between CTCs and their primary tumors and found very high similarities between CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. CTCs also showed some characteristics that were different from those of the primary tumor tissues, suggesting that CTCs evolve some unique characteristics after migrating from the primary tumor; these characteristics may be one of the reasons for the ability of tumor cells to evade immune surveillance.Conclusion: thus, our study provides insight into the potential use of CTCs in pathological classification of NSCLC patients as well as CTC primary tumor inheritance and CTC evolution influence metastasis and immune escape.

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Fangfang Lv ◽  
Liang Sun ◽  
Qiuping Yang ◽  
Zheng Pan ◽  
Yuhua Zhang

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. Methods. Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. Results. A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS ( HR = 1.35 , 95% CI: 1.10-1.64, P = 0.003 ) and a tendency toward an unfavorable OS ( HR = 1.22 , 95% CI: 0.99-1.50, P = 0.068 ). Patients with deletion polymorphism had lower ORR ( OR = 0.60 , 95% CI: 0.42-0.85, P = 0.004 ) and DCR ( OR = 0.59 , 95% CI: 0.38-0.90, P = 0.014 ) compared with those without deletion. Conclusion. BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

Lameck Mbangula Amugongo ◽  
Eliana Vasquez Osorio ◽  
Andrew Frederick Green ◽  
David Cobben ◽  
Marcel van Herk ◽  

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Junliang Zhou ◽  
Mingyan Zhang ◽  
Huanhuan Dong ◽  
Meiqi Wang ◽  
Yue Cheng ◽  

The present study aimed to analyze the effects of acetylation-related lncRNAs in non-small-cell lung cancer (NSCLC). A total of 399 differentially expressed lncRNAs (DElncRNAs) have been identified between 497 NSCLC tissues and 54 normal tissues in the TCGA database, and 105 of which were correlated with acetylation regulators. By using univariate cox regression analysis and combining it with clinical prognosis information, 12 prognostic-related lncRNAs were selected for the subsequent analysis. The NSCLC patients were divided into two subgroups (cluster 1 and cluster 2) by clustering software, and immunocyte infiltration analysis, microenvironmental analysis, and clinical relevance analysis were performed between the two subgroups. A risk model was also built to further assess the prognosis value of prognostic-related lncRNAs in NSCLC patients. We found that AC099850.3 was significantly higher in both cluster 1 and high-risk subgroups, which may serve as a potential biomarker for the prognosis of NSCLC patients. Then, based on ceRNA competition mechanisms, the pathway enrichment of 105 acetylation-related lncRNAs was conducted by GO and KEGG analyses. We found the acetylation-related lncRNAs were primarily enriched in MAPK and EGFR signaling pathways, which were closely associated with NSCLC development. Finally, we validated the expression levels of AC099850.3 in NSCLC tissues and adjacent non-cancerous tissues and confirmed that AC099850.3 was significantly highly expressed in NSCLC tissues and cells. These results may provide clues for our understanding of the role of acetylation-related lncRNAs and valuable information for future clinical diagnosis and prognosis in NSCLC patients.

Jie Zeng ◽  
Xuan Li ◽  
Long Liang ◽  
Hongxia Duan ◽  
Shuanshuan Xie ◽  

Abstract Purpose Cyclase-associated protein 1 (CAP1) is a ubiquitous protein which regulates actin dynamics. Previous studies have shown that S308 and S310 are the two major phosphorylated sites in human CAP1. In the present study, we aimed to investigate the role of CAP1 phosphorylation in lung cancer. Methods Massive bioinformatics analysis was applied to determine CAP1’s role in different cancers and especially in lung cancer. Lung cancer patients’ serum and tissue were collected and analyzed in consideration of clinical background. CAP1 shRNA-lentivirus and siRNA were applied to CAP1 gene knockdown, and plasmids were constructed for CAP1 phosphorylation and de-phosphorylation. Microarray analysis was used for CAP1-associated difference analysis. Both in vitro and in vivo experiments were performed to investigate the roles of CAP1 phosphorylation and de-phosphorylation in lung cancer A549 cells. Results CAP1 is a kind of cancer-related protein. Its mRNA was overexpressed in most types of cancer tissues when compared with normal tissues. CAP1 high expression correlated with poor prognosis. Our results showed that serum CAP1 protein concentrations were significantly upregulated in non-small cell lung cancer (NSCLC) patients when compared with the healthy control group, higher serum CAP1 protein concentration correlated with shorter overall survival (OS) in NSCLC patients, and higher pCAP1 and CAP1 protein level were observed in lung cancer patients’ tumor tissue compared with adjacent normal tissue. Knockdown CAP1 in A549 cells can inhibit proliferation and migration, and the effect is validated in H1975 cells. It can also lead to an increase ratio of F-actin/G-actin. In addition, phosphorylated S308 and S310 in CAP1 promoted lung cancer cell proliferation, migration, and metastasis both in vitro and in vivo. When de-phosphorylated, these two sites in CAP1 showed the opposite effect. Phosphorylation of CAP1 can promote epithelial–mesenchymal transition (EMT). Conclusion These findings indicated that CAP1 phosphorylation can promote lung cancer proliferation, migration, and invasion. Phosphorylation sites of CAP1 might be a novel target for lung cancer treatment.

2021 ◽  
Vol 11 ◽  
Yongsheng Wang ◽  
Feng Jiang ◽  
Ruixue Xia ◽  
Ming Li ◽  
Chengyun Yao ◽  

We reported unique molecular features of cerebrospinal fluid (CSF) of nonsmall cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM), suggesting establishing CSF as a better liquid biopsy in clinical practices. We performed next-generation panel sequencing of primary tumor tissue, plasma, and CSF from 131 NSCLC patients with LM and observed high somatic copy number variations (CNV) in CSF of NSCLC patients with LM. The status of EGFR-activating mutations was highly concordant between CSF, plasma, and primary tumors. ALK translocation was detected in 8.3% of tumor tissues but only 2.4% in CSF and 2.7% in plasma. Others such as ROS1 rearrangement, RET fusion, HER2 mutation, NTRK1 fusion, and BRAF V600E mutation were detected in 7.9% of CSF and 11.1% of tumor tissues but only 4% in plasma. Our study has shed light on the unique genomic variations of CSF and demonstrated that CSF might represent better liquid biopsy for NSCLC patients with LM.

2021 ◽  
Vol 20 (1) ◽  
Cong Ma ◽  
Xiaoyan Wang ◽  
Jingjing Guo ◽  
Ping Liu

Abstract Background Abnormalities in serum lipids and lipoproteins have been documented to link to the risk of cancers in recent years, but its prognostic value for cancer is not known. This study retrospectively evaluated the significance of preoperative serum lipids and lipoproteins for NSCLC’s prognosis. Methods A retrospective review was implemented of 551 patients succumbed to NSCLC. A ROC curve was utilized to determine the best cut-off value and area under the ROC curve. Kaplan-Meier and a Cox proportional hazards model were utilized to perform survival analysis. Results With a median follow-up of 42 months, the NSCLC patients in the high TG (> 1.21 mmol/L) and low HDL-C (≤ 1.26 mmol/L) two groups exhibited shorter OS and DFS. In multivariable analysis, preoperative HDL-C and TG can work as independent prognosis factors for OS (P<0.001 for both) and DFS (P<0.05 for both) in patients succumbed to NSCLC. Conclusion Abnormalities of serum lipids and lipoproteins metabolism linked to the survival outcomes of NSCLC. Preoperative serum HDL-C and TG may be promising biomarkers to predict the NSCLC patients’ prognosis.

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Dr/Khaled Abdel Karim ◽  
Dr/Khaled Nagib ◽  
Dr/Ahmed Hassan Abd El Aziz ◽  
Christina Gamil Garas

Abstract Background Lung cancer is the leading cause of cancer death worldwide, but little is known about how patients with this disease are managed. Aim of the Work We aim to study patterns of care and treatment pathways of non- surgically managed early and locally advanced NSCLC patients from January 2015 to December 2018 in Ain Shams University Clinical Oncology Department. Patients and Methods In this retrospective analysis we included patients the met the following criteria; age &gt;18, histologically confirmed NSCLC patients whom didn’t undergo surgical resection with at least 6 months of follow up data. We collected data from Clinical Oncology department archive in Ain Shams university hospital. Our primary objective is to identify the patterns of care and treatment pathway for non surgically managed NSCLC patients in ASUCOD from January 2015 to December 2018. Results 86 patients finally met our inclusion criteria. Median age at diagnosis of 61 years with a range of (38-85), 95.3% were male. Most of the patients were stage III; 40.7% were stage IIIA, 41.9% were stage IIIB, and 9.3% were stage IIIC. 41 were treated radically, 37 received palliative treatment and only 8 patients received supportive care. Overall median progression free survival in our patients was 9.23 (7.4-13.5) and overall survival duration was13.4 (9.5-18.0). In radically treated patients, 68.3% received sequential chemoradiotherapy (sCRT), 29.2% received concurrent chemoradiotherapy (cCRT) or 2.4% received definitive radiotherapy alone (RT). In palliative treated patients, 73% received chemotherapy alone (CTX), 8.1% received palliative RT and 18.9% received both chemotherapy and palliative dose of radiotherapy (CRT). All treatment modalities were similar regarding median progression free survival and overall survival durations, 17.5 (3.6–19.6) and 20.6 (3.6–31.6) in cCRT, 17.5 (3.6–19.6) and 23.3 (17.7–31.2) in sCRT, 12.9 and 13.4 RT group, P value=0.57 and 0.16 receptively. Similarly, progression free survival and overall survival durations were 8.8 (3.0–15.8) and 16.2 (3.6–18.7) in CRT, 5.3 (0.4–7.6) and 8.6 (6.2–10.2) in CTX, 8.5 (0.4–8.5) and 8.5 (0.4–8.5) in palliative RT group, P value=0.64 and 0.15 receptively. In our study, first-line chemotherapy were Gemcitabine plus Cisplatin (41.9%) or Carboplatin (35.1%).The Second -line chemotherapy were Docetaxel (63.1%) or Paclitaxel plus Carboplatin (26.3%). Paclitaxel plus Carboplatin were the most regimen given with RT. Most of the patients received radiation dose of 60Gy/30Fr (73.2%). Regarding the incidence of toxicity, there were significant high rates of esophagitis in cCRT in grade 3 or more compared to sCRT. Conclusion We have found that less than half of this study population were treated radically while the other half received palliative treatment. And only few patients received best supportive care. Radically treated patients had higher progression free survival and overall survival durations compared to palliative and supportive treatment.

2021 ◽  
Vol 49 (10) ◽  
pp. 030006052110429
Yuling He ◽  
Tongtong An

Several clinical trials have proven that immunotherapy can improve survival and benefit non-small cell lung cancer (NSCLC) patients. In patients who progress after chemotherapy, immune checkpoint inhibitor (ICI) monotherapy can prolong overall survival compared with patients receiving single-agent chemotherapy. A 61-year-old man diagnosed with advanced NSCLC and without driver variants received first-line chemotherapy but experienced recurrence. During subsequent treatment, the disease progressed rapidly, and his general condition deteriorated; therefore, toripalimab monotherapy was initiated. Surprisingly, he responded well, and symptoms were relieved after several treatment cycles despite pseudoprogression, shown in chest images. For driver gene-negative NSCLC patients who progress after chemotherapy and who develop poor performance status (PS), ICIs are an option to alleviate symptoms and improve survival. Furthermore, immunotherapy in patients with pseudoprogression may also provide a survival benefit.

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