scholarly journals 1104 Plasma Circulating Cell-Free Messenger RNA as a Potential Biomarker of Melanoma

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
M Ita ◽  
J H Wang ◽  
N Fanning ◽  
G Kaar ◽  
C Lim ◽  
...  

Abstract Introduction Blood-borne cell-free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with therapeutic response. Method Plasma circulating cell-free messenger ribonucleic acid (ccfmRNA) was extracted from twenty patients with stage IV melanoma receiving immunotherapy. Pathway focused gene expression analysis was performed. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. Response Evaluation Criteria in Solid Tumours (RECIST 1.1) was used for tumour burden estimation. Results In stage IV melanoma patients, CCL5, GZMB and MYD88 genes were significantly over-expressed (p < 0.05 versus healthy controls). In patients with high disease burden or progressive disease, CCL18, CCR1, CCR4, CD274, CSF2, and GBP1 genes were significantly over-expressed (p < 0.05 versus patients with therapeutic response). Finally, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, GBP1, and PTGS2 genes were significantly over-expressed (p < 0.05, versus patients without brain metastasis). Conclusions Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma. CCL4 and CCL5 are prognostic in melanoma, both genes had significantly higher expressions in low disease burden patients compared to patients with a high disease burden.

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
M. I Ita ◽  
J H Wang ◽  
N Fanning ◽  
G F Kaar ◽  
C H Lim ◽  
...  

Abstract Introduction Blood-borne cell-free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with therapeutic response. Method Plasma circulating cell-free messenger ribonucleic acid (ccfmRNA) was extracted from twenty patients with stage IV melanoma receiving immunotherapy. Pathway focused gene expression analysis was performed. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. Response Evaluation Criteria in Solid Tumours (RECIST 1.1) was used for tumour burden estimation. Result In stage IV melanoma patients, CCL5, GZMB and MYD88 genes were significantly over-expressed (P < 0.05 versus healthy controls). In patients with high disease burden or progressive disease, CCL18, CCR1, CCR4, CD274, CSF2, and GBP1 genes were significantly over-expressed (P < 0.05 versus patients with therapeutic response). Finally, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, GBP1, and PTGS2 genes were significantly over-expressed (P < 0.05, versus patients without brain metastasis). Conclusion Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma. CCL4 and CCL5 are prognostic in melanoma, both genes had significantly higher expressions in low disease burden patients compared to patients with a high disease burden. Take-home Message CCL4 and CCL5 ccfmRNA transcripts are prognostic in melanoma. High expression of both genes is favourable in melanoma patients.


2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
M Ita ◽  
JH Wang ◽  
P O'Leary ◽  
Y Nolan ◽  
A Toulouse ◽  
...  

Abstract Introduction Serial monitoring for disease progression and therapeutic efficacy at the molecular level in metastatic melanoma is hampered by a lack of reliable blood borne biomarkers. Molecular profiling of melanoma tumours is almost impractical in metastatic disease due to risks of procedure related morbidity and sampling inefficiency in representing tumour heterogeneity. Cell free DNA allows monitoring of molecular changes in melanoma over the course of immunotherapy. We investigated the utility of somatic mutation and gene amplification analyses in melanoma patients receiving immunotherapy. Method Cell free DNA was extracted from plasma using a QIAamp Circulating Nucleic Acid Kit (Qiagen). Pathway focused profiling of somatic mutation status was performed by ARMs PCR using QBiomarker Somatic Mutation PCR Arrays (Qiagen). Gene amplification analysis was performed by Real Time Quantitative PCR (Roche) using RT2 Profiler PCR Arrays (Qiagen). Result A total of twenty patients with stage IV melanoma receiving immunotherapy were enrolled in this study. The BRAF p.V600E mutation was detected in the cfDNA of 80% of BRAF positive patients. Cell free DNA was also profiled for a total of 84 genes of the cancer inflammation and immunity pathway. There was a significant difference in the copy numbers of several genes (CTLA-4, CXCL12, CXCL5, IDO1, TGFB, IFNG, IL4, PTGS2, AICDA, HLA-A, CCL4, ACKR3, TP53, MYC) between patients with progressive disease and therapeutic response (n=20, p < 0.05). Conclusion We postulate that cell free DNA pathway focused somatic mutation and gene amplification analyses may be useful in evaluating disease progression and therapeutic response. Take-home message Genomic analysis of circulating nucleic acids may be useful in evaluating disease progression and therapeutic response in metastatic melanoma.


2018 ◽  
Vol 38 (11) ◽  
pp. 6393-6397 ◽  
Author(s):  
KALLE MATTILA ◽  
PIRITA RAANTA ◽  
VALTTERI LAHTELA ◽  
SEPPO PYRHÖNEN ◽  
ILKKA KOSKIVUO ◽  
...  

2018 ◽  
Vol 227 (1) ◽  
pp. 116-124 ◽  
Author(s):  
Carolyn S. Hall ◽  
Merrick Ross ◽  
Jessica B. Bowman Bauldry ◽  
Joshua Upshaw ◽  
Mandar G. Karhade ◽  
...  

2014 ◽  
Author(s):  
David Polsky ◽  
Jyothi Sakuntala Tadepalli ◽  
Gregory Chang ◽  
Nathaniel Fleming ◽  
Yongzhao Shao ◽  
...  

2020 ◽  
Vol 18 (11) ◽  
pp. 1270-1277
Author(s):  
Klaus Eisendle ◽  
Georg Weinlich ◽  
Susanne Ebner ◽  
Markus Forstner ◽  
Daniela Reider ◽  
...  

2007 ◽  
Vol 30 (8) ◽  
pp. 831-838 ◽  
Author(s):  
Hitoe Torisu-Itakura ◽  
Jonathan H. Lee ◽  
Young Huynh ◽  
Xing Ye ◽  
Richard Essner ◽  
...  

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 7572-7572
Author(s):  
S. G. Holtan ◽  
R. D. Rao ◽  
E. Creagan ◽  
J. Kaur ◽  
H. Pitot ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8600-8600
Author(s):  
Nicole M. Rochet ◽  
Luis F. Porrata ◽  
Lisa A. Kottschade ◽  
Travis Edward Grotz ◽  
Svetomir Markovic

8600 Background: The prognosis of stage IV melanoma patients remains poor. Published results have suggested that components of the complete blood count have significant prognostic value in several malignancies. Among the most studied were the absolute lymphocyte count (ALC), and absolute monocyte count (AMC) on clinical outcomes of patients with lymphoid malignancies. Thus, we sought to investigate if the pre-operative ALC (ALC-PO), AMC (AMC-PO) and ALC/AMC ratio (ALC/AMC-PO) affects the risk of disease recurrence and survival after complete surgical resection of metastatic melanoma. Methods: We studied 66 stage IV, resected melanoma patients followed at Mayo Clinic from 2000 to 2010. Log rank chi-square analysis was used to determine the best cut-off values for each pre-operative variable, while proportional hazards models were used to compared survival. Results: The median follow-up of the cohort was 24 months (range: 2.3 – 117 months). ALC-PO, AMC-PO and ALC/AMC-PO, as continuous variables, were all identified as prognostic factors for both relapse-free survival (RFS) and overall survival (OS). The best cut-off values for ALC-PO, AMC-PO and ALC/AMC-PO were 1.9; 0.62; and 2.05, respectively. Using Kaplan-Meier analysis, patients with an ALC-PO ≥ 1.9 x 109/L experienced superior OS and RFS compared with ALC-PO < 1.9 x 109/L patients [median OS of 58 months vs. 34 months, p < 0.04; median RFS of 14 months vs. 5 months, p < 0.009]. Conversely, a low AMC-PO (<0.62 x 109/L) was associated with better OS and RFS compared with higher AMC-PO (≥ 0.62 x 109/L): [median OS of 47 months vs. 14 months, p < 0.007; median RFS of 9 months vs. 5 months, p < 0.02]. When the ALC-PO and AMC-PO were combined as an ALC/AMC ratio, the group with an ALC/AMC-PO ≥ 2.05 experienced a superior OS and RFS compared to patients with ALC/AMC-PO < 2.05: [median OS of 49 months vs. 12 months, p < 0.0001; median RFS of 10 months vs. 4 months, p < 0.0001]. Multivariate analysis showed ALC/AMC-PO to be an independent prognostic factor for RFS and OS (HR = 0.32, p < 0.003; HR = 0.23, p < 0.002). Conclusions: Our study showed, that ALC/AMC-PO ratio is an independent prognostic factor for RFS and OS in patients undergoing resection of metastatic (stage IV) melanoma.


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