Abstract 4428
Background
Cutaneous melanoma (CM) deserves prominence among tumors due to its high mortality. Single nucleotide variants (SNVs) in genes of immune system pathways in T lymphocytes and abnormal melanocytes may favor tumor proliferation and progression. The aim of the present study was to verify whether SNVs JAK1 c.1648 + 1272G>A and c.991-27C>T and JAK2 c.-1132G>T and c.-139G>A alter the risk of CM and prognosis of CM patients.
Methods
We analysed 248 patients with CM seen at diagnosis at the General Hospital and 274 blood donors (controls) from the Haematology and Haematology Centre of the University of Campinas (UNICAMP). Genotypes of SNVs were identified in DNA of blood samples by real time polimerase chain reaction (RT-PCR), and gene expressions were evaluated by quantitative PCR (qPCR). The statistical meaning of diferences between groups was calculated by t test and Mann-Whitney test. The logistic regression was used to obtain odds ratio (ORs) adjusted for age, cutaneous phototype, nevi and sun exposure, considering the 95% confidence interval (CI). The progression free survival and overall survival were obtained using the Kaplan-Meier estimates and differences between curves were analyzed by the log-rank test. The prognostic value of each variable in patients survival was verified through the univariate and multivariate Cox analyses.
Results
Patients with the JAK1 c.991-27CC genotype (1,22 vs. 0,75 UA, P = 0,01) and allele C (1,11 vs. 0,75 UA, P = 0,02) showed higher mRNA than others. The median follow-up of CM patients was 93 months (variation: 5-221 months). In univariate Cox analysis, patients with the JAK1 c.1648 + 1272GG and JAK1 c.991-27CC isolated genotypes and JAK1 c.1648 + 1272GG plus JAK1 c.991-27CC combined genotype had 1,78, 1,71 and 1,82 more chances of presenting progression of disease, respectively. Patients with JAK1 c.1648 + 1272GG plus JAK1 c.991-27CC plus JAK2 c.-1132GG plus JAK2 c.-139GG combined genotype had 2,11 more chance of presenting disease progression than others.
Conclusions
Our data suggest, for the first time, that JAK1 c.1648 + 1272G>A and c.991-27C>T and JAK2 c.-1132G>T and c.-139G>A SNVs of the JAK/STAT intracellular signaling pathway can alter JAK1 expression and prognosis of CM patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
CAPES, FAPESP.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2045 - The analysis of treatment sequences and clinical outcomes of thymic carcinoma
Presenter: Arakaki Motoko
Session: Poster Display session 1
Resources:
Abstract
4785 - Transcriptomic Difference of Thymoma and Thymic Carcinoma
Presenter: Naixin Liang
Session: Poster Display session 1
Resources:
Abstract
2864 - A Phase II Trial of Preoperative Chemoradiotherapy and Pembrolizumab for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Presenter: Seoyoung Lee
Session: Poster Display session 1
Resources:
Abstract
5015 - The study of tumor associated exosomes in crosstalk between esophageal carcinoma and lymphatic endothelial cells
Presenter: Weimin Mao
Session: Poster Display session 1
Resources:
Abstract
1339 - Up-regulation of IBSP expression predicts poor prognosis of Esophageal Squamous Cell Carcinoma patients
Presenter: Mingyue Wang
Session: Poster Display session 1
Resources:
Abstract
4083 - PD-L1 expression in primary tumour vs metastatic samples in the Phase 3 MYSTIC study in first-line metastatic (m) NSCLC
Presenter: Niels Reinmuth
Session: Poster Display session 1
Resources:
Abstract
5113 - Assessing the impact of subsequent checkpoint inhibitor (CPI) treatment on overall survival: post hoc analyses from the phase 3 JAVELIN Lung 200 study of avelumab vs docetaxel in platinum-treated locally advanced/metastatic non-small cell lung cancer (NSCLC)
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
4256 - Long-term avelumab treatment in patients with advanced non-small cell lung cancer (NSCLC): post hoc analyses from JAVELIN Solid Tumor
Presenter: Borys Hrinczenko
Session: Poster Display session 1
Resources:
Abstract
4305 - Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: Updated survival and subgroup analysis from the real-world EVIDENS study
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
5128 - IO-Synthesise NSCLC: A pooled analysis of real-world survival outcomes for non-small cell lung cancer patients treated with nivolumab in France and Germany
Presenter: Adrien Dixmier
Session: Poster Display session 1
Resources:
Abstract