scholarly journals Detection of Mitochondrial DNA Copy Number in Plasma Exosomes of Patients with Non-small Cell Lung Cancer

2022 ◽  
Author(s):  
Le Thi Thanh Nhan ◽  
Nguyen Thuy Quynh ◽  
Le Lan Phuong ◽  
Bui Phuong Thao ◽  
Nguyen Thi Tu Linh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Mtdna Copy Number ◽  
Pcr Assay ◽  
Nsclc Patients

For the prevalence of lung cancer and its poor diagnosis, the seeking of the efficient biomarkers for this disease is an urgent requirement, especially from non-invasive samples such as plasma. The mitochondria DNA (mtDNA) copy number change has been evaluated as a potential indicator of cancer risk, however, there have been few studies regarding mtDNA in plasma derived exosomes. In this study, the mtDNA copy number was measured on 29 plasma exosome samples of patients with non-small cell lung cancer (NSCLC) and 29 plasma exosome samples of cancer-free controls by real-time PCR assay, then being statistically analyzed to evaluate the relationship between these figures and several pathological features of NSCLC patients. As the results, the existence of mtDNA in exosomes isolated from plasma was detected through PCR assay using primers covering most of the mtDNA length. The relative mtDNA copy numbers determined in the exosomes of the disease and control groups were 1619.1 ± 2589.0 and 1207.0 ± 1550.0, respectively, whereas these values in two disease stages were 783.6 ± 759.3 (stage I-II) and 2647.0 ± 3584.0 (stage III-IV). Comparing among these groups, the difference was only statistically significant between the disease groups of stage I-II and stage III-IV (p<0.05), the group of stage III-IV and the control group (p<0.05). Indeed, the mtDNA copy number is associated with tumor stage and stage N (p<0.05). On the other aspect, the smoking habit of NSCLC patients could be an underlying reason behind the alteration in mtDNA copy number in the plasma exosomes. In short, our study demonstrates that the mtDNA copy number in exosomes resourced from plasma could be a potential biomarker for the detection and prognosis of NSCLC.

ALK amplification and crizotinib sensitivity in non-small cell lung cancer cell lines and patients report.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10556-10556 ◽  
Author(s):  
Kalai Khadija ◽  
Nathalie Auger ◽  
Beranger Lueza ◽  
Frederic Commo ◽  
Alexander Valent ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Cancer Cell Lines ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

10556 Background: ALK high copy number (HCN) seems to be a frequent event, described in 13-17% of Non-small cell lung cancer (NSCLC). The goal of this study was to describe ALK genomic aberrations on NSCLC patients and cell lines, to explore the ALK HCN response to crizotinib through in vitro assays and to report three patients case. Methods: 191 Paraffin embedded specimens from advanced NSCLC patients and 27 NSCLC cancer cell lines were screened for ALK copy number by fluorescent in situ hybridization (FISH). Crizotinib sensitivity was evaluated in 9 cell lines through WST1 assays and clonogenic tests. Three patients exhibiting ALK HCN were assessed for response to crizotinib. Results: EML4-ALK translocation was present in 22 pts (11.5%). 21 pts (11%) exhibited over 6 copies of ALK. 6 (22%) cell lines displayed more than 5 copies of ALK, 19 (70%) presented a gain of 3 or 4 ALK copy number, only one cell line exhibited normal ALK copies and one harbored EML4-ALK translocation. FISH with CEP2 revealed a polysomy of chromosome 2 in cases with ALK HCN.Out of the 9 cell lines tested, 4 ALK HCN cell lines (H661, A427, BEN, H1299) exhibited increased sensitivity for crizotinib vs. 3 low ALK copy number (LCN) cell lines (H1975, H1651, H1650) with a low sensitivity. Median IC50 with crizotinib values was1750 nM [300-2800nM] in ALK HCN cell lines vs 4500 nM [800-8000nM] in ALK LCN cell lines, p=0.35. 3 patients with ALK HCN tumor received crizotinib ( in 4th , 5th and 6th -line therapy) for 2, 3 and 5 months with stable disease as best response and clinical benefit in 2 pts. Conclusions: ALK HCN may predict sensitivity to crizotinib. A clinical study is planned in ALK HCN pts.

Genomic correlates and classification of PD-L1 status in non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21578-e21578
Author(s):  
Feng Liang ◽  
Sisi Liu ◽  
Ya Jiang ◽  
Xiuxiu Xu ◽  
Qiuxiang Ou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Small Cell ◽  
Small Cell Lung ◽  
Oncogenic Mutations ◽  
Nsclc Patients ◽  
L1 Protein

e21578 Background: Programmed cell death 1 (PD-L1) is the first FDA-approved predictive biomarker for non-small cell lung cancer (NSCLC) patients treated with PD-(L)1 blockade therapy. Herein, we aim to identify potential anti-PD-L1 treatment-related biomarkers through evaluating the correlation between the PD-L1 expression level, clinical characteristics, and the mutational profile of a large Chinese NSCLC cohort. Methods: Genomic profiling of tumor biopsies from a total of 808 Chinese NSCLC patients, including 651 adenocarcinomas (ADCs) and 157 squamous cell carcinomas (SCCs), was performed using next-generation sequencing by targeting 425 cancer-relevant genes. Immunohistochemical analysis was used to evaluate PD-L1 protein expression using PD-L1 antibodies including DAKO 22C3 ( N= 695) and DAKO 28-8 ( N= 113), respectively. Results: The PD-L1 positive ( > 1%) rate was 49.2% in ADCs and 52.9% in SCCs, respectively. PD-L1 expression (22C3) was associated with the male gender( p< 0.01) and lymph node metastasis ( p= 0.048) in ADCs but not in SCC patients. PD-L1 expression (22C3) was inversely correlated with KRAS wildtype ( p< 0.001) and EGFR exon 19 deletion( p< 0.01) in ADC, while it was negatively associated with TP53 oncogenic mutations ( p= 0.049) in SCC. Copy number variation analysis revealed that MDM2 amplification ( p= 0.027), 1q gain ( p= 0.012), and 5q deletion ( p< 0.01) negatively correlated with PD-L1 expression, whereas PD-L1 and PD-L2 amplification ( p< 0.001 and p< 0.0001) were positively associated with PD-L1 expression in ADCs. In SCCs, PD-L1 expression (22C3) was negatively associated with copy number gain in EGFR ( p= 0.040), MDM2 ( p= 0.044), 14q ( p= 0.032), and 20q ( p= 0.026), along with PTPRD loss (p = 0.015) and 19p deletion (p = 0.025). However, it was positively associated with 9p amplification ( p< 0.01) and 13q deletion ( p= 0.019). Plus, KIF5B- RET ( p= 0.006) appeared to be inversely related to the PD-L1 expression levels (22C3) in ADCs alone. In addition, these predicted biomarkers were used to delineate the receiver operating characteristic (ROC) calculation to discriminate between PD-L1 low and high (22C3, 50%) with an AUC score of 0.779. Lastly, PD-L1 expression (28-8) did not show significant correlation with any detected oncogenic mutations, but negatively correlated with NKX2-1 gain ( p= 0.0379) and 9q deletion ( p= 0.0379) in ADCs. Conclusions: This study revealed the correlation between PD-L1 protein expression, clinical features, and mutational traits in NSCLC patients, and provided a classifier for PD-L1 expression prediction.

scholarly journals Achievement of Long-term Local Control After Concurrently With Radiation and Anti-PD-1 Immunotherapy in Locally Advanced Non-small Cell Lung Cancer Patients

2020 ◽  
Author(s):  
zhao jing ◽  
Rongjin Zhou ◽  
Huaxiang He ◽  
Shixiu Wu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Case Series ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background: Although concurrent chemoradiotherapy (CRT) was recommend as standard of care in patients with stage III unresectable non-small cell lung cancer (NSCLC), many patients refused or were not eligible for chemotherapy in clinical practice. These patients often receive RT alone with 5-year OS rate of about 5-6%. This addressed a common clinical challenge of treating these patients. Immune-checkpoint inhibitors have demonstrated objective antitumor responses in patients with advanced NSCLC, but it is unclear how these agents can be used in the curative therapy with concurrent radiation. Case presentation: Here we described, the case series, the effect of stage III unresectable NSCLC patients who refused chemotherapy received radiation and anti-PD-1 immunotherapy. Three patients with stage III unresectable NSCLC were treated with radiotherapy concurrently with anti-PD-1 agent (pembrolizumab) between May 2018 and August 2018 in our hospital. Two patients experienced partial response and one patient experienced stable disease. One patient developed the liver metastasis 4 months after the treatment. All patients had no local-regional recurrence. No patient experienced ≥ grade 3 adverse event (AE), and no patient discontinued treatment because of an AE. Conclusions: Concurrent treatment with radiation and pembrolizumab for unresectable stage III NSCLC patients who refused chemotherapy demonstrated its efficacy and acceptable tolerance. Further investigations are warranted to determine its role in the management of these patients.

Effect of increased MET gene copy number on survival of surgically resected non-small cell lung cancer (NSCLC) patients

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 11047-11047 ◽  
Author(s):  
F. Cappuzzo ◽  
M. Skokan ◽  
S. Gajapathy ◽  
L. Giordano ◽  
M. Incarbone ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung ◽  
Nsclc Patients

Postoperative survivin expression in stage III non-small cell lung cancer (NSCLC) patients treated with neoadjuvant chemoradiation.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 7034-7034
Author(s):  
M. J. Fidler ◽  
S. Basu ◽  
K. A. Kaiser-Walters ◽  
E. Hadziahmetovic ◽  
M. Batus ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survivin Expression ◽  
Neoadjuvant Chemoradiation ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Nsclc Patients

Utility of surveillance imaging in stage III non-small cell lung cancer (NSCLC) patients: A SEER-Medicare analysis.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 8531-8531
Author(s):  
Manish K. Thakur ◽  
Julie Ruterbusch ◽  
Ann G. Schwartz ◽  
Jennifer Lynn Beebe-Dimmer ◽  
Andreana N Holowatyj ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Surveillance Imaging ◽  
Nsclc Patients

Factors affecting treatment in small cell and non-small cell lung cancer patients.

2019 ◽  
Vol 37 (27_suppl) ◽  
pp. 146-146
Author(s):  
Phuong Ngo ◽  
Christina M Pinkston ◽  
Goetz H. Kloecker
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Stage Iii ◽  
Stage At Diagnosis ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Nsclc Patients

146 Background: Kentucky has the highest incidence of lung cancer death and despite improvements in treatment and survival, some small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients remain untreated. We looked at factors preventing these patients from receiving necessary treatment. Methods: Data was collected from the Kentucky Cancer Registry (KCR) for SCLC and NSCLC patients from 2012-2015 and included race, gender, age at diagnosis, treatment history, insurance and overall survival. Treatment included any combination of surgery, radiation, chemotherapy or immunotherapy. Patient demographics were summarized based on treatment status and derived odds ratio (OR) and 95% confidence intervals (CI) were reported. Significant associations were assessed at the p < 0.05 level. Results: KCR identified 2,992 SCLC and 13,975 NSCLC patients from 2012-2015. More NSCLC patients [3,608 (25.8%)] were untreated than SCLC patients [621 (20.8%), p < 0.001], and untreated patients overall were more likely to be older, have more comorbidities (SCLC only), and have Medicare, Medicaid or no insurance. Stage at diagnosis was also a factor but differed based on histology. NSCLC stage III and stage IV patients had higher odds of being untreated compared to stage I (Stage III OR: 2.91, 95% CI: 2.57-3.28; Stage IV OR: 4.82, 95% CI: 4.29-5.41) where these odds in SCLC patients were non-significant (Stage III OR: 0.94, 95% CI: 0.56-1.55) or lower (Stage IV OR: 1.61, 95% CI: 1.01-2.55). SCLC patients also had lower odds of delayed treatment (defined as > 4 weeks to treatment) in stage III and stage IV compared to stage I (Stage III OR: 0.33, 95% CI: 0.23-0.48; Stage IV OR: 0.27, 95% CI: 0.20-0.38). Conclusions: This study shows an overall significant number of untreated lung cancer patients with treatment being strongly associated with insurance status, histology and stage at diagnosis. SCLC patients are more likely to be treated than NSCLC, and advanced stage is less a factor in treating SCLC than NSCLC. The difference may be due to the more aggressive nature of SCLC with physicians feeling more urgency to treat SCLC given its rapid progression and chemotherapy sensitivity compared to NSCLC.

scholarly journals Survival Outcomes with Photodynamic Therapy, Chemotherapy and Radiation in Patients with Stage III or Stage IV Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 803 ◽  
Author(s):  
Sumedha Chhatre ◽  
Anil Vachani ◽  
Ron R. Allison ◽  
Ravishankar Jayadevappa
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Photodynamic Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Nsclc Patients

Data regarding the association between photodynamic therapy (PDT) and mortality in lung cancer patients are limited. We analyzed the association between PDT and mortality in patients with stage III or IV non-small cell lung cancer (NSCLC) using data from the National Cancer Database (NCDB) between 2004 and 2016. From the NCDB, we identified patients receiving laser ablation/cryosurgery or local tumor destruction/excision (which includes PDT). From Medicare and Medicaid claims between 2000 and 2013, we identified NSCLC patients receiving PDT and those receiving bronchoscopy, then used these to confirm the PDT treatment. From NCDB, we extracted NSCLC patients who received radiation with chemotherapy, radiation alone or chemotherapy alone. We used survival analysis to determine the association between PDT and mortality. Between 2004 and 2016, 457,556 NSCLC patients with stage III or stage IV were identified, of which 147 received PDT with radiation and chemotherapy, 227,629 received radiation with chemotherapy, 106,667 had radiation therapy alone and 122,193 received chemotherapy alone. Compared to the radiation alone group, the PDT group and radiation with chemotherapy group had lower hazard of mortality (50% and 53% lower, respectively). Among the NSCLC patients with stage III or stage IV disease, the addition of PDT to radiation therapy offers survival benefit over radiation therapy alone.

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