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Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma.

ABSTRACT: BACKGROUND:The tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC). METHODS:Using multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients. RESULTS:Eight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p<0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95%?CI 2.619 to 12.006; p<0.0001) and progression-free survival (HR 2.798, 95%?CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95%?CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed. CONCLUSIONS:The immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT.

SUBMITTER: Liu SL

PROVIDER: S-EPMC7204817 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma.

Liu Sai-Lan SL Bian Li-Juan LJ Liu Ze-Xian ZX Chen Qiu-Yan QY Sun Xue-Song XS Sun Rui R Luo Dong-Hua DH Li Xiao-Yun XY Xiao Bei-Bei BB Yan Jin-Jie JJ Lu Zi-Jian ZJ Yan Shu-Mei SM Yuan Li L Tang Lin-Quan LQ Li Jian-Ming JM Mai Hai-Qiang HQ

Journal for immunotherapy of cancer 20200401 1

<h4>Background</h4>The tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC).<h4>Methods</h4>Using multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shri ...[more]

PMID: 32303611

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Project description:BackgroundThe global burden of hepatocellular carcinoma (HCC) is increasing, negatively impacting social health and economies. The discovery of novel and valuable biomarkers for the early diagnosis and therapeutic guidance of HCC is urgently needed.MethodsExtracellular matrix (ECM)-related gene sets, transcriptome data and mutation profiles were downloaded from the Matrisome Project and The Cancer Genome Atlas (TCGA)-LIHC datasets. Coexpression analysis was initially performed with the aim of identifying ECM-related lncRNAs (r > 0.4, p < 0.001). The screened lncRNAs were subjected to univariate analysis to obtain a series of prognosis-related lncRNA sets, which were incorporated into least absolute selection and shrinkage operator (LASSO) regression for signature establishment. Following the grouping of LIHC samples according to risk score, the correlations between the signature and clinicopathological, tumour immune infiltration, and mutational characteristics as well as therapeutic response were also analysed. lncRNA expression levels used for modelling were finally examined at the cellular and tissue levels by real-time PCR. All analyses were based on R software.ResultsAL031985.3 and MKLN1-AS were ultimately identified as signature-related lncRNAs, and both were significantly upregulated in HCC tissue samples and cell lines. The prognostic value of the signature reflected by the AUC value was superior to that of age, sex, grade and stage. Correlation analysis results demonstrated that high-risk groups exhibited significant enrichment of immune cells (DCs, macrophages and Tregs) and increased expression levels of all immune checkpoint genes. Prominent differences in clinicopathological profiles, immune functions, tumour mutation burden (TMB) and drug sensitivity were noted between the two risk groups.ConclusionsOur signature represents a valuable predictive tool in the prognostic management of HCC patients. Further validation of the mechanisms involved is needed.

Dataset Information

Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma.

Publications

Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma.

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