Publications by authors named "Haoyu Lyu"

3 Publications

  • Page 1 of 1

Subtyping of head and neck squamous cell cancers based on immune signatures.

Int Immunopharmacol 2021 Oct 28;99:108007. Epub 2021 Jul 28.

Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

Although head and neck squamous cell cancer (HNSCC) is one of the cancer types in which immune checkpoint inhibitors (ICIs) has achieved a certain success, only a subset of HNSCC patients respond to ICIs. Thus, identification of HNSCC subtypes responsive to ICIs is crucial. Using hierarchical clustering, we identified three subtypes of HNSCC, termed Immunity-H, Immunity-M, and Immunity-L, based on the enrichment scores of 28 immune cells generated by the single-sample gene-set enrichment analysis of transcriptome data. We demonstrated that this subtyping method was stable and producible in four different HNSCC cohorts. Immunity-H had the highest levels of immune infiltrates and PD-L1 expression, lowest levels of stemness, intratumor heterogeneity and genomic instability, and favorable prognosis. In contrast, Immunity-L had the lowest levels of immune infiltrates and PD-L1 expression, highest levels of stemness, intratumor heterogeneity and genomic instability, and unfavorable prognosis. We found that somatic copy number alteration had a significant negative association with anti-tumor immunity in HNSCC, while tumor mutation burden showed no significant association. TP53, COL11A1, NSD1, and PKHD1L1 were more frequently mutated in Immunity-H versus Immunity-L, and their mutations were associated with increased immune signatures in HNSCC. Besides immune-related pathways, many stromal and oncogenic pathways were highly enriched in Immunity-H, including cell adhesion molecules, focal adhesion, ECM-receptor interaction, calcium signaling, MAPK signaling, apoptosis, VEGF signaling, and PPAR signaling. The high levels of PD-L1 expression and immune infiltration in Immunity-H indicate that this subtype responds best to ICIs. Our study recaptures the immunological heterogeneity in HNSCC and provide clinical implications for the immunotherapy of HNSCC.
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http://dx.doi.org/10.1016/j.intimp.2021.108007DOI Listing
October 2021

Comparisons of the immunological landscape between COVID-19, influenza, and respiratory syncytial virus patients by clustering analysis.

Comput Struct Biotechnol J 2021 23;19:2347-2355. Epub 2021 Apr 23.

Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Background: COVID-19 has stronger infectivity and a higher risk for severity than most other contagious respiratory illnesses. The mechanisms underlying this difference remain unclear.

Methods: We compared the immunological landscape between COVID-19 and two other contagious respiratory illnesses (influenza and respiratory syncytial virus (RSV)) by clustering analysis of the three diseases based on 27 immune signatures' scores.

Results: We identified three immune subtypes: Immunity-H, Immunity-M, and Immunity-L, which displayed high, medium, and low immune signatures, respectively. We found 20%, 35.5%, and 44.5% of COVID-19 cases included in Immunity-H, Immunity-M, and Immunity-L, respectively; all influenza cases were included in Immunity-H; 66.7% and 33.3% of RSV cases belonged to Immunity-H and Immunity-L, respectively. These data indicate that most COVID-19 patients have weaker immune signatures than influenza and RSV patients, as evidenced by 22 of the 27 immune signatures having lower enrichment scores in COVID-19 than in influenza and/or RSV. The Immunity-M COVID-19 patients had the highest expression levels of  and  and lowest viral loads and were the youngest. In contrast, the Immunity-H COVID-19 patients had the lowest expression levels of  and  and highest viral loads and were the oldest. Most immune signatures had lower enrichment levels in the intensive care unit (ICU) than in non-ICU patients. Gene ontology analysis showed that the innate and adaptive immune responses were significantly downregulated in COVID-19 versus healthy individuals.

Conclusions: Compared to influenza and RSV, COVID-19 displayed significantly different immunological profiles. Elevated immune signatures are associated with better prognosis in COVID-19 patients.
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http://dx.doi.org/10.1016/j.csbj.2021.04.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062909PMC
April 2021

Correlate the Mutation and the Mutation with Immune Signatures in Head and Neck Squamous Cell Cancer.

Comput Struct Biotechnol J 2019 26;17:1020-1030. Epub 2019 Jul 26.

Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Although immunotherapy has emerged as an effective therapeutic strategy for various cancers including head and neck squamous cell carcinomas (HNSCCs), only a subset of patients can benefit from such therapy. Hence, it is pressing to discover predictive biomarkers for cancer immunotherapy response. and mutations frequently occur in HNSCC and correlate with a worse prognosis in HNSCC. We extensively characterized the associations of mutations and mutations with HNSCC immunity based on multiple cancer genomics datasets. We compared the enrichment levels of 20 immune signatures between -mutated and -wildtype HNSCCs, and between -mutated and -wildtype HNSCCs, and found that mutations were associated with depressed immune signatures while mutations were associated with enhanced immune signatures in HNSCC. Moreover, we found multiple p53- and RAS-mediated pathways showing significant correlations with HNSCC immunity. Furthermore, we demonstrated that the association between mutation and tumor immunity was independent of the human papillomavirus (HPV) infection and smoking status in HNSCC. These data suggest that p53 and RAS may play important roles in regulating HNSCC immunity and that the and mutation status could be useful biomarkers for stratifying HNSCC patients responsive to immunotherapy.
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http://dx.doi.org/10.1016/j.csbj.2019.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695281PMC
July 2019
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