Abstract 2171
Background
Copy number alterations in cyclin D1 (CCND1) relevant to malignant biological behavior exist in solid tumors, including head and neck squamous cell cancer (HNSCC). The prevalence and utility of CCND1 amplification as a biomarker for the clinical response to immune checkpoint inhibitors (ICIs) therapy is unknown.
Methods
This was a three-cohort pooled study, 6904 samples from 6540 patients from the Geneplus Insitute, 10562 samples from the TCGA and 10614 samples from the MSKCC were statistically analyzed. Next-generation sequencing assays were performed in tumor samples at the Geneplus Institute. Genomic, transcriptomic, and clinical data were obtained from TCGA and MSKCC. Comprehensive profiling was performed to determine the prevalence of CCND1 amplification and their correlation with the prognosis and the response to ICIs. Assessment of the CCND1 amplification frequency, overall survival (OS), gene set enrichment analysis (GSEA) and immune profile in solid tumors.
Results
In HNSCC, 7 cases (25.00%) were identified CCND1 amplification in the Chinese cohort, 120 cases (23.21%) in the TCGA cohort, and 5 cases (9.43%) in the MSKCC cohort. Survival analysis showed that CCND1 amplification was an independent prognostic factor for poor outcome in HNSCC as well as for pan-cancer in the TCGA and MSKCC populations. Furthermore, in the MSKCC cohort, patients receiving ICIs with CCND1 amplification had a shorter OS compared with neutral patients (HR, 1.63; 95%CI, 1.09–2.43; median OS, 11.0m vs. 18.0m; P = .0024), especial in the high-TMB subgroup (HR, 2.82; 95%CI, 1.11–7.20; median OS, 10.0m vs. 41.0m; P = .0003). Comparing the transcriptome between amplification and neutral groups in six solid tumors from the TCGA cohort showed various degrees of immunosuppression in the tumor microenvironment (TME), especially in HNSCC. The GSEA suggested that multiple aggressive, immunosuppressive and angiogenic hallmarks correlate with CCND1 amplification in HNSCC.
Conclusions
These findings indicate that CCND1 amplification may be a key point related to immunosuppression in TME and multiple malignancy hallmarks, and it hinders not only the natural host immune responses but also the efficacy of ICIs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Chuan Ben Chen.
Funding
Ministry of Health P.R.China (Grant No. WKJ2016-2-33).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3290 - Identification of meningioma patients in high risk of tumor recurrence using microRNA profiling
Presenter: Josef Srovnal
Session: Poster Display session 3
Resources:
Abstract
2477 - Antecedent of cancer and mortality after the first ST segment elevation acute myocardial infarction treated with primary coronary angioplasty. A prospective cohort study
Presenter: Irene Sillero
Session: Poster Display session 3
Resources:
Abstract
1894 - Genomic characterisation of locally advanced pancreatic adenocarcinoma
Presenter: Sarah Picardo
Session: Poster Display session 3
Resources:
Abstract
3280 - Comparison of freshly prepared and frozen cells from colorectal cancer surgical samples for phenotyping experiments- a pilot study
Presenter: Sandra Mersakova
Session: Poster Display session 3
Resources:
Abstract
3419 - Hyaluronan (HA) Accumulation in the Tumor Microenvironment (TME) is Increased in Colorectal Cancer (CRC) and Associated with Consensus Molecular Subtypes (CMS) 4 Molecular Subtype
Presenter: Barbara Blouw
Session: Poster Display session 3
Resources:
Abstract
1833 - Evaluation of CT-based radiomics in patients with renal cell carcinoma
Presenter: An Zhao
Session: Poster Display session 3
Resources:
Abstract
5883 - Detection of Double Protein Expression in Diffuse Large B Cell Lymphoma
Presenter: Mohamed Gouda
Session: Poster Display session 3
Resources:
Abstract
5415 - Encyclopedic Tumor Analysis for organ agnostic treatment with Axitinib in combination regimens for advanced cancers
Presenter: Tim Crook
Session: Poster Display session 3
Resources:
Abstract
3297 - Computational model to predict response rate of clinical trials
Presenter: Orsolya Lorincz
Session: Poster Display session 3
Resources:
Abstract
4355 - Analysis of BRCA genes and homologous recombination deficiency (HRD) scores in tumours from patients (pts) with metastatic breast cancer (mBC) in the OlympiAD trial
Presenter: Mark Robson
Session: Poster Display session 3
Resources:
Abstract