scholarly journals A Proteomic Approach to the Identification of Lung Cancer Markers

2001 ◽  
Vol 17 (4) ◽  
pp. 295-300 ◽  
Author(s):  
Samir Hanash ◽  
Franck Brichory ◽  
David Beer

We have developed a comprehensive approach to the identification of protein markers in lung cancer that includes profiling of tumor tissue and cell lines as well as the analysis of serum for autoantibodies to lung tumor antigens. A large number of proteins that are differentially expressed in the major subtypes of lung cancer have been identified by mass spectrometry. A database of protein expression in lung cancer and other types of cancer has been constructed that integrates two-dimensional gel profiles, mass spectrometry data, quantitative protein data and gene expression data at the RNA level, that serves as a resource for biomarker identification. Analysis of the serological response in lung cancer has led to the identification of novel markers detectable in serum of lung cancer patients at the time of diagnosis. The proteomic approach is likely to yield novel classification schemes and novel markers for early diagnosis of lung cancer.

2020 ◽  
Author(s):  
Lingling Wan ◽  
Yutong He ◽  
Qingyi Liu ◽  
Di Liang ◽  
Yongdong Guo ◽  
...  

Abstract Background: Lung cancer is a malignant tumor that has the highest morbidity and mortality rate among all cancers. Early diagnosis of lung cancer is a key factor in reducing mortality and improving prognosis. Methods: In this study, we performed CTC next-generation sequencing (NGS) in early-stage lung cancer patients to identify lung cancer-related gene mutations. Meanwhile, a serum liquid chromatography-tandem mass spectrometry (LC-MS) untargeted metabolomics analysis was performed in the CTC-positive patients, and the early diagnostic value of these assays in lung cancer was analyzed. Results: 62.5% (30/48) of lung cancer patients had ≥ 1 CTC. By CTC NGS, we found that > 50% of patients had 4 commonly mutated genes, namely, NOTCH1, IGF2, EGFR, and PTCH1. 47.37% (9/19) patients had ARIDH1 mutations. Additionally, 30 CTC-positive patients and 30 healthy volunteers were subjected to LC-MS untargeted metabolomics analysis. We found 100 different metabolites, and 10 different metabolites were identified through analysis, which may have potential clinical application value in the diagnosis of CTC-positive early-stage lung cancer (AUC > 0.9). Conclusions: Our results indicate that NGS of CTC and metabolomics may provide new tumor markers for the early diagnosis of lung cancer. This possibility requires more in-depth large-sample research for verification.


The Analyst ◽  
2020 ◽  
Vol 145 (2) ◽  
pp. 313-320 ◽  
Author(s):  
Haiyan Lu ◽  
Hua Zhang ◽  
Yiping Wei ◽  
Huanwen Chen

Lipids, metabolites and proteins in a bulk tissue were sequentially detected by iEESI-MS for improved accuracy in cancer differentiation.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13103-e13103
Author(s):  
Kang-Yi Su ◽  
Bing-Ching Ho ◽  
Gee-Chen Chang ◽  
Hsuan-Yu Chen ◽  
Pan-Chyr Yang ◽  
...  

e13103 Background: Approximately 3-7% of lung tumors harbor anaplastic lymphoma kinase (ALK) fusions in the subgroup of non-small cell lung cancer (NSCLC). In addition to echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion, TRK-fused gene (TFG)-ALK, kinesin family member 5B (KIF5B)-ALK and kinesin light chain 1 (KLC1)-ALK had been reported in lung cancer. On the other hand, RET proto-oncogene (RET) and ROS proto-oncogene 1 (ROS1) fusion proteins also have prevalence in lung cancer. Food and Drug Administration (FDA)-approved several target drugs are available to treat patients with fusion mutations. Therefore, the diagnosis of ALK, RET or ROS1 fusion genes shows quite important. However, nowadays methods of detecting fusions such as fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are limited to technique, low sensitivity, sample quality as well as subtype classification. Methods: We established nucleotide MALDI-TOF mass spectrometry based multiplex detection platform to distinguish major types including 9 types of EML4-ALK, 5 types of ALK, 5 types of RET and 8 types ROS1 fusions. Results: The detection limitation was about less 1% mutant cells among wild-type cells. In the pilot testing, we used 2 patients’ cell cDNA and 4 patients’ lung FFPE samples cDNA, which had been diagnosed as ALK fusion before, to be detected by this panel, and then identified their variant types successfully. Furthermore, one patient harbored CCDC6-RET fusion mutation was identified by our platform and confirmed by Sanger Sequencing. Conclusions: Taken together, this new panel has high sensitivity and allows little and poor quality samples for detecting. The correlation between clinical characteristics and fusion subtypes can be further investigated by utilizing this platform in the future. Also, the detection panel can be revised based on clinical needs by removing/adding probes.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20016-e20016
Author(s):  
Christopher Peter Adams ◽  
Wasif M. Saif

e20016 Background: : Despite the recent success of checkpoint inhibitors, there continues to be a significant medical need for lung cancer therapies that can be directed to the patients most likely to respond. Somatostatin receptor subtype 2 (SSTR2) is the most widely up-regulated subtype in both small and non-small cell lung cancers and is also expressed in tumoral (but not mature) blood vessels. Peptide targeted radiotherapy has advantages over traditional targeted therapies in that targeted tumor cells as well as surrounding cancer cells and supporting stroma are selectively killed. This study was conducted to determine the ability of Rhenium Re 188 P2045, a radiolabeled somatostatin analog specific for SSTR2 to both image (to select the most appropriate patients) and treat lung cancer patients who over-express somatostatin receptors. Methods: In an open label, single arm study, refractory lung cancer patients to standard of care therapy were identified by image analysis using Rhenium Re 188 P2045, a radiolabeled somatostatin analog. 25 Patients received the imaging dose of 10uCi of Re188 and 265ng of peptide by intravenous injection. Three patients were selected based on high SSTR expression levels to receive 30uCi of Re188 P2045 as a therapeutic dose 14 days after imaging. Patients were followed for 8 weeks post treatment. Results: The imaging study revealed a high density of expression of the somatostatin receptor in the lungs of patients. Patients in the imaging and therapeutic treatment groups reported no adverse advents or signs of toxicity. The image analysis using Re188 P2045 was compared to CT images and demonstrated accurate detection of lung tumor lesions. The images obtained using Re188 P2045 were of sufficiently high quality to enable identification of receptor expression at the tumor site as shown in Figures 1&2. Conclusions: Rhenium Re 188 P2045, a radiolabeled somatostatin analog, may be used to both identify and treat lung cancer tumors. The ability to image and dose patients with the same targeted molecule enables a personalized medicine approach and this highly targeted patient therapy may significantly improve treatment of tumors that over express somatostatin receptor.


2019 ◽  
pp. 3-7
Author(s):  
I. О. Vynnychenko ◽  
Yu. V. Moskalenko ◽  
O. І. Vynnychenko ◽  
M. Yu. Serdyuk ◽  
O. А. Ternovenko

Lung cancer is one of the major causes of death from malignancies. That is why the article devoted to the issue early diagnosis of lung cancer. The objective of the work is to consider the features and prospects of using the most modern methods of diagnosis of lung cancer. The introduction of the latest technologies is essential for quality screening of lung cancer patients. Gradually, there is a growing interest in developing strategies around the world to better assess the risk of human lung cancer, increase screening sensitivity, and reduce costs. The methods of early detection of lung cancer are described in the article: determination of the concentration of volatile organic compounds (LuCID method), endobronchial ultrasound (EBUS method), FISH-marker method, basic principles of the Nano-Nose device. Despite some advances in our country in the diagnosis of lung cancer using common advanced methods of computed tomography and biopsy, the introduction of foreign experience in lung cancer screening is necessary, because the current state-of-the-art methods of diagnosis allow to detect cancer.


2021 ◽  
Author(s):  
Luv Khandelwal ◽  
Housne Begum ◽  
Pria Nippak

Abstract Objective Most cancer deaths in the world are due to lung cancer and delays in diagnosis and treatment sharply reduce survival in lung cancer patients. This study examined the impact of delays during the early months of the pandemic on the survival of newly identified lung cancer patients in Canada in 2020. Methods The incidence of lung cancer, using population statistics from Statistics Canada and incidence rates from the Canadian Cancer Statistics in 2020, was estimated. Stage-wise incidences for each sex were calculated for each age group for each month of 2020. Using delay impact on each stage the final results were calculated. Results A total of 5,004 life years would have been lost due to 448 deaths in the long term (40 months) attributed to the delays caused during March, April, May and June in Canada. The estimated incidence for all stages of lung cancer for these months was 9,801 although the observed incidence was expected to be 6,571 due to reduced screenings. Hence, it was within the missing 3,231 cases that delays would occur. Over the short term (10 months) there are expected to be 151 early deaths and 273 deaths in the intermediate-term (20 months). Conclusion The COVID pandemic is estimated to result in increased mortality and fewer diagnosis’ of lung cancer patients in Canada in 2020.


Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6145
Author(s):  
Svetlana E. Novikova ◽  
Natalia A. Soloveva ◽  
Tatiana E. Farafonova ◽  
Olga V. Tikhonova ◽  
Pao-Chi Liao ◽  
...  

The proteins of extracellular vesicles (EVs) that originate from tumors reflect the producer cells’ proteomes and can be detected in biological fluids. Thus, EVs provide proteomic signatures that are of great interest for screening and predictive cancer diagnostics. By applying targeted mass spectrometry with stable isotope-labeled peptide standards, we assessed the levels of 28 EV-associated proteins, including the conventional exosome markers CD9, CD63, CD81, CD82, and HSPA8, in vesicles derived from the lung cancer cell lines NCI-H23 and A549. Furthermore, we evaluated the detectability of these proteins and their abundance in plasma samples from 34 lung cancer patients and 23 healthy volunteers. The abundance of TLN1, TUBA4A, HSPA8, ITGB3, TSG101, and PACSIN2 in the plasma of lung cancer patients was measured using targeted mass spectrometry and compared to that in plasma from healthy volunteers. The most diagnostically potent markers were TLN1 (AUC, 0.95), TUBA4A (AUC, 0.91), and HSPA8 (AUC, 0.88). The obtained EV proteomic signature allowed us to distinguish between the lung adenocarcinoma and squamous cell carcinoma histological types. The proteomic cargo of the extracellular vesicles represents a promising source of potential biomarkers.


Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1344
Author(s):  
Karsten M. Heil ◽  
Matthias Helmschrott ◽  
Fabrice F. Darche ◽  
Tom Bruckner ◽  
Philipp Ehlermann ◽  
...  

Long-term survival after heart transplantation (HTX) is impacted by adverse effects of immunosuppressive pharmacotherapy, and post-transplant lung cancer is a common occurrence. This study aimed to examine the risk factors, treatment, and prognosis of patients with post-transplant lung cancer. We included 625 adult patients who received HTX at Heidelberg Heart Center between 1989 and 2018. Patients were stratified by diagnosis and staging of lung cancer after HTX. Analysis comprised donor and recipient characteristics, medications including immunosuppressive drugs, and survival after diagnosis of lung cancer. A total of 41 patients (6.6%) were diagnosed with lung cancer after HTX, 13 patients received curative care and 28 patients had palliative care. Mean time from HTX until diagnosis of lung cancer was 8.6 ± 4.0 years and 1.8 ± 2.7 years from diagnosis of lung cancer until last follow-up. Twenty-four patients (58.5%) were switched to an mTOR-inhibitor after diagnosis of lung cancer. Multivariate analysis showed recipient age (HR: 1.05; CI: 1.01–1.10; p = 0.02), COPD (HR: 3.72; CI: 1.88–7.37; p < 0.01), and history of smoking (HR: 20.39; CI: 2.73–152.13; p < 0.01) as risk factors for post-transplant lung cancer. Patients in stages I and II had a significantly better 1-year (100.0% versus 3.6%), 2-year (69.2% versus 0.0%), and 5-year survival (53.8% versus 0.0%) than patients in stages III and IV (p < 0.01). Given the poor prognosis of late-stage post-transplant lung cancer, routine reassessment of current smoking status, providing smoking cessation support, and intensified lung cancer screening in high-risk HTX recipients are advisable.


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