The validity of 5-aminorevrinic acid as a biomarker for risk screening and supportive diagnostic parameters in lung cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21027-e21027
Author(s):  
Yoshikane Yamauchi ◽  
Yuichi Saito ◽  
Koji Murakami ◽  
Yasuyuki Kanamoto ◽  
Momoko Asami ◽  
...  

e21027 Background: Early detection and treatment of cancer is an important issue that affect the prognosis of cancer patients. Photodynamic screening with 5-aminorevrinic acid (ALA-PDS) is simple and non-invasive procedure for risk screening of cancer, and it is gradually recognized as the predictable biomarkers for cancer in Japan. In this study, we examined the predictability of lung cancer by ALA-PDS and its usefulness as a supportive parameter for preoperative diagnosis. Methods: Eighty-five lung cancer patients (48 males and 37 females) just before lung resection were enrolled. 5-aminolevulinic acid phosphate 150mg was taken at night and urine samples were collected in the next morning. The porphyrin metabolites in the urine samples were detected by solid phase extraction method, previously reported from our group. Afterwards, the data was adjusted depending renal function. The data was compared with that from healthy volunteer without any abnormal symptom and physical disorder. Results: The average age of 85 patients was 70 years (46-85). The number of patients in each pathological stage was 2 in Stage 0, 58 in Stage IA and IB, 15 in Stage IIA and IIB, 8 in Stage IIIA and IIIB, and 2 in Stage IV, respectively. The diagnosis was 61 cases of adenocarcinoma and 22 cases of squamous cell carcinoma. Urinary porphyrin metabolites in lung cancer patients increased significantly as compared to those of healthy volunteers (2,847nM/gCRE vs 1,668nM/gCRE, p < 0.001). Increase of urinary porphyrin metabolites was observed even in stage 0 or I patients, but the correlation with stage progression was not clear (Stage 0 and I vs Stage II vs Stage III and IV: 2,757nM/gCRE vs 3,099nM/gCRE vs 3,010nM/gCRE). Furthermore, urinary porphyrin metabolites were confirmed to be significantly increased even in PET-negative cancer patients, compared to healthy volunteers (p < 0.001). Conclusions: ALA-PDS was able to predict lung cancer in our cohort. Moreover, it was also suggested that it may be useful as a supportive parameter for diagnosis of early stage lung cancer or PET negative lung cancer.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19072-e19072
Author(s):  
A. Irigoyen ◽  
C. Olmedo ◽  
J. Valdivia ◽  
A. Comino ◽  
C. Cano ◽  
...  

e19072 Background: The gene expression profile in peripheral blood samples from lung cancer patients is a potential predictor to treatment response. Methods: The study has been developed using 10 healthy volunteers as the control group and 10 lung cancer patients (stage IV). Written informed consent was obtained being the protocol approved by the local Clinical Research and Ethics Committee. Peripheral blood samples were obtained from lung cancer patients before (T0) and after treatment (T15d). RNA from peripheral blood samples was extracted and purified selecting 28S/18S ratios>1.5 to obtain cDNA and cRNA for hybridization of the 20,000 genes included in Human 20K CodeLink. An array from each participant was obtained in duplicate. For each array, 2 μg of cRNA was compared to 2 μg of healthy cRNA.. Significant genes were found using Significance Analysis of Microarrays which uses repeated permutations of the data. Results: The selected genes were expressed >3-fold with a false discovery rate =0.05. Before treatment (T0) when patients were compared to healthy volunteers there was an increase in the expression of: histone 1 H4c, transforming growth factor beta 2, endothelial cell growth factor 1 (platelet-derived), glucose-6-phosphatase catalytic 2, Relaxin 3 receptor 1, Insulin-like growth factor binding protein 2, RAS-like family 11 member B, and ELK4. After treatment (T15d), when each lung cancer patient's results were compared to their own before treatment results (T0), there was an increase in the expression of: Bcl2, myosin light polypeptide 4; interferon alpha-inducible protein 27; interferon gamma receptor 1; RASSF5, ARHGEF6, IGFBP5, tumor protein p53 inducible nuclear protein 1, peroxisome proliferative activated receptor gamma. Conclusions: The data presented identifies biologically relevant over-expressed genes in lung cancer. A validation of these results and the analysis of the genes that identify patients who will respond positively to erlotinib treatment is being carried out. No significant financial relationships to disclose.


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.


BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e028448 ◽  
Author(s):  
Wenwen Li ◽  
Wei Dai ◽  
Mingxin Liu ◽  
Yijing Long ◽  
Chunyan Wang ◽  
...  

IntroductionLung cancer is the most common cancer and the leading cause of cancer death in China, as well as in the world. Late diagnosis is the main obstacle to improving survival. Currently, early detection methods for lung cancer have many limitations, for example, low specificity, risk of radiation exposure and overdiagnosis. Exhaled breath analysis is one of the most promising non-invasive techniques for early detection of lung cancer. The aim of this study is to identify volatile organic compound (VOC) biomarkers in lung cancer and to construct a predictive model for lung cancer based on exhaled breath analysis.Methods and analysisThe study will recruit 389 lung cancer patients in one cancer centre and 389 healthy subjects in two lung cancer screening centres. Bio-VOC breath sampler and Tedlar bag will be used to collect breath samples. Gas chromatography-mass spectrometry coupled with solid phase microextraction technique will be used to analyse VOCs in exhaled breath. VOC biomarkers with statistical significance and showing abilities to discriminate lung cancer patients from healthy subjects will be selected for the construction of predictive model for lung cancer.Ethics and disseminationThe study was approved by the Ethics Committee of Sichuan Cancer Hospital on 6 April 2017 (No. SCCHEC-02-2017-011). The results of this study will be disseminated in presentations at academic conferences, publications in peer-reviewed journals and the news media.Trial registration numberChiCTR-DOD-17011134; Pre-results.


2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
Y Nishina ◽  
M Niino ◽  
T Higashi

Abstract Background The health hazards of asbestos have been globally recognized, especially those among industrial workers with long-term exposure. Lung cancer is one such asbestos-related disease. It occurs not only among workers but also among residents with environmental exposure to asbestos. Patients with work-related exposure can receive occupational compensation, and patients with non-occupational exposure are supported by a separate compensation system in Japan. However, the latter is not well-known among clinicians, and a substantial number of patients may have been left out. We need an effective way to find patients eligible to receive benefits by better understanding the clinical conditions that characterize patients with asbestos-related lung cancer. Methods We conducted two types of research: 1. Comparison of clinical characteristics between compensation system recipients (N = 65) and general lung cancer patients diagnosed in 2015, using Japan’s National Database of Hospital-Based Cancer Registry. 2. Estimation of the frequency of pleural plaques among lung cancer patients by double-checking CT scan images of a random sample of lung cancer patients obtained from the HBCR national database (N = 3585). Results Patients with squamous cell carcinoma are twice as likely asbestos-induced as patients with other histology overall after adjusting for age, sex and cancer stages, but not smoking status and history. As many as 20% of the CT images were read inconsistently between two radiologists or respiratory disease doctors and we could not obtain the accurate rate of candidacy for the compensation system. Conclusions We require more accurate information about pathological characteristics by controlling for smoking status and history among compensation recipients. For radiologic interpretation, more effective education is needed for the radiologists and respiratory disease doctors who treat lung cancer patients. Key messages Specific information about asbestos-related lung cancer would lead clinicians to correctly identify asbestos-related lung cancer. Educational system for clinicians would help patients to receive the benefit of compensation.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Charlotte Feil ◽  
Frank Staib ◽  
Martin R. Berger ◽  
Thorsten Stein ◽  
Irene Schmidtmann ◽  
...  

Abstract Background Lung cancer is the most common oncological cause of death in the Western world. Early diagnosis is critical for successful treatment. However, no effective screening methods exist. A promising approach could be the use of volatile organic compounds as diagnostic biomarkers. To date there are several studies, in which dogs were trained to discriminate cancer samples from controls. In this study we evaluated the abilities of specifically trained dogs to distinguish samples derived from lung cancer patients of various tumor stages from matched healthy controls. Methods This single center, double-blind clinical trial was approved by the local ethics committee, project no FF20/2016. The dog was conditioned with urine and breath samples of 36 cancer patients and 150 controls; afterwards, further 246 patients were included: 41 lung cancer patients comprising all stages and 205 healthy controls. From each patient two breath and urine samples were collected and shock frozen. Only samples from new subjects were presented to the dog during study phase randomized, double-blinded. This resulted in a specific conditioned reaction pointing to the cancer sample. Results Using a combination of urine and breath samples, the dog correctly predicted 40 out of 41 cancer samples, corresponding to an overall detection rate of cancer samples of 97.6% (95% CI [87.1, 99.9%]). Using urine samples only the dog achieved a detection rate of 87.8% (95% CI [73.8, 95.9%]). With breath samples, the dog correctly identified cancer in 32 of 41 samples, resulting in a detection rate of 78% (95% CI [62.4, 89.4%]). Conclusions It is known from current literature that breath and urine samples carry VOCs pointing to cancer growth. We conclude that olfactory detection of lung cancer by specifically trained dogs is highly suggestive to be a simple and non-invasive tool to detect lung cancer. To translate this approach into practice further target compounds need to be identified.


2021 ◽  
Vol 12 ◽  
Author(s):  
Liangliang Wu ◽  
Shengzhi Xie ◽  
Lingxiong Wang ◽  
Jinfeng Li ◽  
Lu Han ◽  
...  

Antibodies against checkpoint inhibitors such as anti-programmed cell death protein 1 (PD-1) and its ligand anti-programmed death ligand 1 (PD-L1) have shown clinical efficacy in the treatment of multiple cancers. However, there are only a few studies on biomarkers for these targeted immunotherapies, especially in peripheral blood. We first studied the role of interferon-induced protein-10 (IP10) combined with interleukin-8 (IL-8) in peripheral blood as a biomarker of immune-combined chemotherapy for lung cancer and multiple cancers. We used the high-throughput cytokine detection platform and performed bioinformatics analysis of blood samples from 67 patients with lung cancer and 24 with multiple cancers. We selected the ratio of IP-10 to IL-8 (S2/S0, ratio of changes at 10–12 weeks after treatment to baseline) to predict the response to immunotherapy combined with chemotherapy and evaluate the survival of lung cancer patients and mixed cancer patients. In patients treated with the combination therapy, the specificity and sensitivity of IL-8 and IP10 together as predictors were improved compared with those of IL-8 and IP10 alone. Our conclusion was verified in not only lung cancer but also multiple cancer research cohorts. We then further validated the predictive effect of biomarkers in different histologic types of NSCLC and chemotherapy combined with different PD-1 drug groups. Subsequent validation should be conducted with a larger number of patients. The proposed marker IP10 (S2/S0)/IL-8 (S2/S0), as a predictive immunotherapy biomarker, has broad prospects for future clinical applications in treating patients with multiple intractable neoplasms.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3515-3515
Author(s):  
Isabelle Borget ◽  
Guy Meyer ◽  
Florian Scotté ◽  
Nicolas Martelli ◽  
Alexandre Vainchtock ◽  
...  

Abstract Background: Venous Thromboembolic Event (VTE) is a common complication for cancer patients, leading to hospitalizations that increase the burden of cancer management. We evaluated the incidence and costs of VTE-related hospitalizations for patients with colon cancer (CC) or lung cancer (LC). Methods: The French national hospital database (PMSI) was analyzed in order to identify patients whose colon cancer or lung cancer was diagnosed in 2010 and who were hospitalized for a VTE at least once during the following two years. The numbers of stays induced by a VTE, and the corresponding number of patients hospitalized, were determined using the disease-specific ICD-10 codes. Associated hospital costs were estimated from the perspective of the third-party payer, using the French official tariffs, on the 1,111 and 1,641 hospitalizations with VTE classified as primary or related diagnosis only (PD / RD) for colon and lung cancer patients, respectively. Results: We identified 47,954 new patients with colon cancer and 39,454 new patients with lung cancer; in each group, 2,866 (6.0%) and 3,775 (9.6%), respectively, were hospitalized for a VTE or had a VTE during their hospital stay. During the 2 years of follow-up of these 6,641 patients, 1,707 (25.7%) were hospitalized for a VTE recurrence. In total, 4,104 stays for CC patients and 5,962 stays for LC patients were analyzed, including stays for recurrence. In colon cancer patients, the mean cost per stay for a VTE classified as PD / RD amounted to 3,612 Euros and 3,457 Euros for first event and recurrence, respectively, and in lung cancer patients, to 3,674 Euros and 3,222 Euros for first event and recurrence, respectively. During the time of the study, mean hospitalization cost per patient who had at least one stay for recurrence was 5,441 Euros and 5,676 Euros in colon and lung cancer, respectively. Over a 2-year period, the total cost of hospital stays induced by VTEs classified as PD / RD reached 3.99 million Euros and 5.90 million Euros for colon and lung cancer, respectively, including a total amount of 1.49 million Euros for VTE recurrence. Conclusion: In colon and lung cancer patients, VTE-related hospitalizations remain frequent and induce an elevated cost. This economic burden may be reduced by decreasing the occurrence of thromboembolic complications, using adequate prophylaxis and efficient management in this at-risk population. Table: Cost of VTE-related hospital stays for patients with colon cancer or lung cancer 1st event Recurrence Global(1st event and recurrence) Colon cancer Mean cost/stay (Euros) 3,612 3,457 3,588 Total cost (Euros) 3,377,219 608,499 3,985,718 Lung cancer Mean cost/stay (Euros) 3,674 3,222 3,599 Total cost (Euros) 5,022,549 879,492 5,902,041 Disclosures Borget: LEO Pharma: Honoraria. Meyer:LEO Pharma: Research Funding. Scotté:LEO Pharma: Honoraria. Martelli:LEO Pharma: Honoraria. Vainchtock:HEVA: Research Funding.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14612-e14612
Author(s):  
Fiona Margaret McCarthy ◽  
Juliana Candido ◽  
Robin Rudd ◽  
Jeremy P. C. Steele ◽  
Frances Balkwill

e14612 Background: Amphiregulin is an EGFR ligand which contributes to many of the hallmarks of cancer including angiogenesis and metastasis. Recent studies demonstrate that Amphiregulin promotes an immunosuppressive tumour microenvironment by modulating the expression of T regulatory cells. Although its expression has been described on a variety of immune cells and tumour cells, there is no published data on Amphiregulin expression by monocytes to date. Previous work by this group has demonstrated that monocytes from non-small cell lung cancer patients are phenotypically and genomically different compared to healthy volunteers. This study aims to further investigate the differing genomic profile of monocytes in non-small cell lung cancer. Methods: Gene expression profiling was performed on CD14++CD16- (classical) monocytes of newly diagnosed patients with Stage IV non-small cell lung cancer (n = 6) and age-matched healthy volunteers (n = 6) using Affymetrix Human U133 Plus 2.0 array. Validation of differentially expressed genes of interest (including Amphiregulin) at mRNA level was performed using real-time PCR with TaqMan gene expression assays on independent patient (n = 6) and healthy volunteer cohorts (n = 6). Differential protein expression of Amphiregulin from the monocytes of healthy volunteers (n = 3) and non-small cell lung cancer patients (n = 3) was validated using ELISA technology. Results: Amphiregulin is one of the most upregulated genes on classical monocytes in non-small cell lung cancer patients compared to healthy volunteers (p = 0.001). The increased expression of Amphiregulin was confirmed on qPCR validation in an independent cohort of non-small cell lung cancer patients (p < 0.05) as well as in the original group (p < 0.001). Amphiregulin was also found to be increased at protein level on CD14++CD16- monocytes of non-small cell lung cancer compared to healthy volunteers. (p = 0.37). Conclusions: Amphiregulin is overexpressed by classical monocytes in non-small cell lung cancer and this over-expression is confirmed at mRNA and protein level. The production of Amphiregulin has not been ascribed to human monocytes in non-small cell lung cancer making its overexpression in this study a unique finding.


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