Faculty Collaboration Database

Analysis of the whole transcriptome from gingivo-buccal squamous cell carcinoma reveals deregulated immune landscape and suggests targets for immunotherapy. PLoS One 2017;12(9):e0183606

Date

09/09/2017

Pubmed ID

28886030

Pubmed Central ID

PMC5590820

DOI

10.1371/journal.pone.0183606

Scopus ID

2-s2.0-85029295065 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

BACKGROUND: Gingivo-buccal squamous cell carcinoma (GBSCC) is one of the most common oral cavity cancers in India with less than 50% patients surviving past 5 years. Here, we report a whole transcriptome profile on a batch of GBSCC tumours with diverse tobacco usage habits. The study provides an entire landscape of altered expression with an emphasis on searching for targets with therapeutic potential.

METHODS: Whole transcriptomes of 12 GBSCC tumours and adjacent normal tissues were sequenced and analysed to explore differential expression of genes. Expression changes were further compared with those in TCGA head and neck cohort (n = 263) data base and validated in an independent set of 10GBSCC samples.

RESULTS: Differentially expressed genes (n = 2176) were used to cluster the patients based on their tobacco habits, resulting in 3 subgroups. Immune response was observed to be significantly aberrant, along with cell adhesion and lipid metabolism processes. Different modes of immune evasion were seen across 12 tumours with up-regulation or consistent expression of CD47, unlike other immune evasion genes such as PDL1, FUT4, CTLA4 and BTLA which were downregulated in a few samples. Variation in infiltrating immune cell signatures across tumours also indicates heterogeneity in immune evasion strategies. A few actionable genes such as ITGA4, TGFB1 and PTGS1/COX1 were over expressed in most samples.

CONCLUSION: This study found expression deregulation of key immune evasion genes, such as CD47 and PDL1, and reasserts their potential as effective immunotherapeutic targets for GBSCC, which requires further clinical studies. Present findings reiterate the idea of using transcriptome profiling to guide precision therapeutic strategies.

Author List

Singh R, De Sarkar N, Sarkar S, Roy R, Chattopadhyay E, Ray A, Biswas NK, Maitra A, Roy B

Author

Navonil De Sarkar PhD Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Carcinoma, Squamous Cell
Cell Cycle
Cell Proliferation
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Immunotherapy
India
Male
MicroRNAs
Mouth Neoplasms
Transcriptome