Sphingosine kinase‑1 predicts overall survival outcomes in non‑small cell lung cancer patients treated with carboplatin and navelbine

Gachechiladze, Mariam; Tichý, Tomáš; Kolek, Vı́tězslav; Grygárková, Ivona; Klein, Jiří; Mgebrishvili, Giorgi; Kharaishvili, Gvantsa; Janíková, Mária; Smičková, Petra; Cierna, L.; Pitson, Stuart M.; Maddelein, Marie‐Lise; Cuvillier, Olivier; Škarda, Jozef

doi:10.3892/ol.2019.10447

Cited by 25 publications

(34 citation statements)

References 39 publications

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“…There are many examples of SK1 upregulation at the mRNA and protein level, which is often associated with poor prognosis including reduced survival and earlier disease recurrence in cancer patients [2]. Recent examples include melanoma [62], papillary thyroid carcinoma [84], non-small cell lung cancer [85], triple-negative breast cancer [86] and colorectal cancer [87]. This is consistent with the ability of SK1 to promote cell survival, proliferation and neoplastic transformation and supports the therapeutic potential of SK1 inhibitors.…”

Section: Sk1/sk2 and Cancermentioning

confidence: 57%

Recent advances in the role of sphingosine 1‐phosphate in cancer

Pyne

2020

FEBS Letters

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Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to a family of G protein-coupled receptors (S1P 1-5) and intracellular targets, such as HDAC1/ 2, that are functional in normal and pathophysiologic cell biology. There is a significant role for sphingosine 1-phosphate in cancer underpinning the socalled hallmarks, such as transformation and replicative immortality. In this review, we survey the most recent developments concerning the role of sphingosine 1-phosphate receptors, sphingosine kinase and S1P lyase in cancer and the prognostic indications of these receptors and enzymes in terms of diseasespecific survival and recurrence. We also provide evidence for identification of new therapeutic approaches targeting sphingosine 1-phosphate to prevent neovascularisation, to revert aggressive and drug-resistant cancers to more amenable forms sensitive to chemotherapy, and to induce cytotoxicity in cancer cells. Finally, we briefly describe current advances in the development of isoform-specific inhibitors of sphingosine kinases for potential use in the treatment of various cancers, where these enzymes have a predominant role. This review will therefore highlight sphingosine 1-phosphate signalling as a promising translational target for precision medicine in stratified cancer patients.

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Section: Sk1/sk2 and Cancermentioning

confidence: 57%

Recent advances in the role of sphingosine 1‐phosphate in cancer

Pyne

2020

FEBS Letters

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“… 43 Furthermore, it was reported that high SPHK1 expression is associated with shorter overall survival and increased risk of disease relapse in patients with NSCLC treated with adjuvant chemotherapy in recent study. 44 Ectopic expression of SPHK1 in NSCLC cells dramatically enhances their resistance to apoptosis induced by doxorubicin or docetaxel, 2 commonly used chemotherapeutics, whereas suppressing SPHK1 expression with small-hairpin RNAs or inhibiting SPHK1 activity with a specific SPHK1 inhibitor (SK1-I) markedly abrogated the ability of NSCLC cells to resist cytotoxic reagent-induced cell death, suggesting that SPHK1 activity contributes to sustaining the unwanted survival of NSCLC cells under the treatment of chemotherapeutics. In fact, injection of SK1-I potently enhanced the tumor suppression effect to docetaxel, a clinically well-established, proapoptotic chemotherapy drug against breast, ovarian, and NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Sphingosine Kinase 1 in Nonsmall Cell Lung Cancer

Motono

Ueda

Shimasaki

et al. 2021

Clin Med�Insights�Pathol

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Bioactive sphingolipid is clearly relevant to lung physiology. The relationship of the bioactive sphingolipid pathway to pulmonary disease has been studied in cellular, tissue, and animal model, including lung cancer models. The samples of 53 patients diagnosed with nonsmall cell lung carcinoma (NSCLC) between June 2009 and May 2014 at our hospital were analyzed. Immunohistochemical (IHC) analysis was performed. The degree of immunostaining was reviewed and scored. Using this method of assessment, we evaluated the IHC score of sphingosine kinase 1 (SPHK1), vimentin, E-cadherin, and Ki-67. Both invasive adenocarcinoma cell and squamous cell carcinoma cell were well stained by SPHK1, and fibroblasts were also well stained by SPHK1. Although the IHC score of SPHK1 was not significantly differed between invasive adenocarcinoma and squamous cell carcinoma, the IHC scores of fibroblast, vimentin, and Ki-67 were higher in squamous cell carcinoma than invasive adenocarcinoma. Correlation among IHC scores in each of invasive adenocarcinoma and squamous cell carcinoma was performed. SPHK1 had positive correlation with both fibroblast and Ki-67, and fibroblast and Ki-67 had also positive correlation in invasive adenocarcinoma. On the contrary, SPHK1 had no significant correlation with fibroblast, and had negative correlation with Ki-67 in squamous cell carcinoma. Although there was not significant prognostic difference in SPHK1 score ( P = .09), IHC score high group tended to be worse on relapse-free survival. SPHK1 might be prognostic factor in lung-invasive adenocarcinoma and novel target for drug against lung-invasive adenocarcinoma.

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“…Our functional enrichment analysis suggests that the genes in our prognostic signature are widely involved in the immune process. Among all the 21 prognostic genes, 14 (e.g., AQP3, BIRC5, C5AR1, HMOX1, IL32, IL6ST, MIF, MMP12, PLAUR , PMAIP1, RAC1, SMAD6, SPHK1, USP7) have been reported to be served as a prognostic biomarker or suggested to be a novel therapeutic targets for lung adenocarcinoma [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67]. The remaining 7 genes, including ARF6, C7, ELF4, ITPR1, MOV10, PTCH1 and RIPK2, have not been previously reported to be associated with LUAD prognosis and might act as potential biomarker.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma

Zheng

Wang

et al. 2020

J Transl Med

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Background The incidence of stage I and stage II lung adenocarcinoma (LUAD) is likely to increase with the introduction of annual screening programs for high-risk individuals. We aimed to identify a reliable prognostic signature with immune-related genes that can predict prognosis and help making individualized management for patients with early-stage LUAD. Methods The public LUAD cohorts were obtained from the large-scale databases including 4 microarray data sets from the Gene Expression Omnibus (GEO) and 1 RNA-seq data set from The Cancer Genome Atlas (TCGA) LUAD cohort. Only early-stage patients with clinical information were included. Cox proportional hazards regression model was performed to identify the candidate prognostic genes in GSE30219, GSE31210 and GSE50081 (training set). The prognostic signature was developed using the overlapped prognostic genes based on a risk score method. Kaplan–Meier curve with log-rank test and time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic value and performance of this signature, respectively. Furthermore, the robustness of this prognostic signature was further validated in TCGA-LUAD and GSE72094 cohorts. Results A prognostic immune signature consisting of 21 immune-related genes was constructed using the training set. The prognostic signature significantly stratified patients into high- and low-risk groups in terms of overall survival (OS) in training data set, including GSE30219 (HR = 4.31, 95% CI 2.29–8.11; P = 6.16E−06), GSE31210 (HR = 11.91, 95% CI 4.15–34.19; P = 4.10E−06), GSE50081 (HR = 3.63, 95% CI 1.90–6.95; P = 9.95E−05), the combined data set (HR = 3.15, 95% CI 1.98–5.02; P = 1.26E−06) and the validation data set, including TCGA-LUAD (HR = 2.16, 95% CI 1.49–3.13; P = 4.54E−05) and GSE72094 (HR = 2.95, 95% CI 1.86–4.70; P = 4.79E−06). Multivariate cox regression analysis demonstrated that the 21-gene signature could serve as an independent prognostic factor for OS after adjusting for other clinical factors. ROC curves revealed that the immune signature achieved good performance in predicting OS for early-stage LUAD. Several biological processes, including regulation of immune effector process, were enriched in the immune signature. Moreover, the combination of the signature with tumor stage showed more precise classification for prognosis prediction and treatment design. Conclusions Our study proposed a robust immune-related prognostic signature for estimating overall survival in early-stage LUAD, which may be contributed to make more accurate survival risk stratification and individualized clinical management for patients with early-stage LUAD.

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Sphingosine kinase‑1 predicts overall survival outcomes in non‑small cell lung cancer patients treated with carboplatin and navelbine

Cited by 25 publications

References 39 publications

Recent advances in the role of sphingosine 1‐phosphate in cancer

Recent advances in the role of sphingosine 1‐phosphate in cancer

Prognostic Impact of Sphingosine Kinase 1 in Nonsmall Cell Lung Cancer

Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma

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