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Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data.

De Cecco L, Nicolau M, Giannoccaro M, Daidone MG, Bossi P, Locati L, Licitra L, Canevari S - Oncotarget (2015)

Bottom Line: Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal.Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes.The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes.

View Article: PubMed Central - PubMed

Affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is a disease with heterogeneous clinical behavior and response to therapies. Despite the introduction of multimodality treatment, 40-50% of patients with advanced disease recur. Therefore, there is an urgent need to improve the classification beyond the current parameters in clinical use to better stratify patients and the therapeutic approaches. Following a meta-analysis approach we built a large training set to whom we applied a Disease-Specific Genomic Analysis (DSGA) to identify the disease component embedded into the tumor data. Eleven independent microarray datasets were used as validation sets. Six different HNSCC subtypes that summarize the aberrant alterations occurring during tumor progression were identified. Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal. Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes. The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes. To conclude, we report a robust molecularly defined subtype classification in HNSCC that can improve patient selection and pave the way to the development of appropriate therapeutic strategies.

No MeSH data available.


Related in: MedlinePlus

Comparison of genome-wide molecular pattern between our and previously reported subtype classificationThe analysis was performed using Subclass Mapping. A. MetaHNC-A is compared with the molecular subtypes defined by Walter et al. ((48); GSE39368). B. MetaHNC-A is compared to the subtypes reported by Chung et al. ((47); GSE686). Red color indicates high confidence for correspondence (p < 0.05); blue color indicates lack of correspondence. BA, basal; MS, mesenchymal; AT, atypical; CL, classical subtypes in the study by Walter et al. G1, G2, G3, G4 refer to the four subtypes identified in the study by Chung et al. C. Table summarizing the correspondence between our subtyping classification and those previously published for HNSCC by Chung et al. (47) and Walter et al. (48).
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Figure 4: Comparison of genome-wide molecular pattern between our and previously reported subtype classificationThe analysis was performed using Subclass Mapping. A. MetaHNC-A is compared with the molecular subtypes defined by Walter et al. ((48); GSE39368). B. MetaHNC-A is compared to the subtypes reported by Chung et al. ((47); GSE686). Red color indicates high confidence for correspondence (p < 0.05); blue color indicates lack of correspondence. BA, basal; MS, mesenchymal; AT, atypical; CL, classical subtypes in the study by Walter et al. G1, G2, G3, G4 refer to the four subtypes identified in the study by Chung et al. C. Table summarizing the correspondence between our subtyping classification and those previously published for HNSCC by Chung et al. (47) and Walter et al. (48).

Mentions: We investigated whether and to what extent the molecular classification described in the present study corresponded to those reported by the two previous studies addressing this issue, Chung et al. [16] and Walter et al. [17]. By Subclass Mapping, we assessed the overall concordance comparing: (i) the classification outlined above to that of Walter et al. (Figure 4A); (ii) he classification outlined above to that of Chung et al. (Figure 4B). The subtyping scheme from the previous studies did not show a one-to-one match with classification outlined above (Figure 4C), providing evidence that our meta-analysis is able to add a finer distinction not achievable with fewer samples (n = 60 for GSE686 and n = 138 for GSE39368). Whilst the Mesenchymal and Classical classifications proposed by Walter et al. and the G2 and G4 subtypes proposed by Chung et al. correspond to our Cl2-Mesenchymal and Cl5-Classical, the Basal and G1 subtypes proposed by Walter et al. and Chung et al. respectively showed molecular patterns split between our Cl3-Hypoxia associated and Cl4-Defense response subtypes. Furthermore, the atypical subtype proposed by Walter et al. is split between our Cl1-HPV-like and Cl6-immunoreactive subtypes, whereas the G3 subtype proposed by Chung et al. corresponds to the Cl1-HPV-like cluster.


Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data.

De Cecco L, Nicolau M, Giannoccaro M, Daidone MG, Bossi P, Locati L, Licitra L, Canevari S - Oncotarget (2015)

Comparison of genome-wide molecular pattern between our and previously reported subtype classificationThe analysis was performed using Subclass Mapping. A. MetaHNC-A is compared with the molecular subtypes defined by Walter et al. ((48); GSE39368). B. MetaHNC-A is compared to the subtypes reported by Chung et al. ((47); GSE686). Red color indicates high confidence for correspondence (p < 0.05); blue color indicates lack of correspondence. BA, basal; MS, mesenchymal; AT, atypical; CL, classical subtypes in the study by Walter et al. G1, G2, G3, G4 refer to the four subtypes identified in the study by Chung et al. C. Table summarizing the correspondence between our subtyping classification and those previously published for HNSCC by Chung et al. (47) and Walter et al. (48).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496244&req=5

Figure 4: Comparison of genome-wide molecular pattern between our and previously reported subtype classificationThe analysis was performed using Subclass Mapping. A. MetaHNC-A is compared with the molecular subtypes defined by Walter et al. ((48); GSE39368). B. MetaHNC-A is compared to the subtypes reported by Chung et al. ((47); GSE686). Red color indicates high confidence for correspondence (p < 0.05); blue color indicates lack of correspondence. BA, basal; MS, mesenchymal; AT, atypical; CL, classical subtypes in the study by Walter et al. G1, G2, G3, G4 refer to the four subtypes identified in the study by Chung et al. C. Table summarizing the correspondence between our subtyping classification and those previously published for HNSCC by Chung et al. (47) and Walter et al. (48).
Mentions: We investigated whether and to what extent the molecular classification described in the present study corresponded to those reported by the two previous studies addressing this issue, Chung et al. [16] and Walter et al. [17]. By Subclass Mapping, we assessed the overall concordance comparing: (i) the classification outlined above to that of Walter et al. (Figure 4A); (ii) he classification outlined above to that of Chung et al. (Figure 4B). The subtyping scheme from the previous studies did not show a one-to-one match with classification outlined above (Figure 4C), providing evidence that our meta-analysis is able to add a finer distinction not achievable with fewer samples (n = 60 for GSE686 and n = 138 for GSE39368). Whilst the Mesenchymal and Classical classifications proposed by Walter et al. and the G2 and G4 subtypes proposed by Chung et al. correspond to our Cl2-Mesenchymal and Cl5-Classical, the Basal and G1 subtypes proposed by Walter et al. and Chung et al. respectively showed molecular patterns split between our Cl3-Hypoxia associated and Cl4-Defense response subtypes. Furthermore, the atypical subtype proposed by Walter et al. is split between our Cl1-HPV-like and Cl6-immunoreactive subtypes, whereas the G3 subtype proposed by Chung et al. corresponds to the Cl1-HPV-like cluster.

Bottom Line: Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal.Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes.The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes.

View Article: PubMed Central - PubMed

Affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is a disease with heterogeneous clinical behavior and response to therapies. Despite the introduction of multimodality treatment, 40-50% of patients with advanced disease recur. Therefore, there is an urgent need to improve the classification beyond the current parameters in clinical use to better stratify patients and the therapeutic approaches. Following a meta-analysis approach we built a large training set to whom we applied a Disease-Specific Genomic Analysis (DSGA) to identify the disease component embedded into the tumor data. Eleven independent microarray datasets were used as validation sets. Six different HNSCC subtypes that summarize the aberrant alterations occurring during tumor progression were identified. Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal. Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes. The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes. To conclude, we report a robust molecularly defined subtype classification in HNSCC that can improve patient selection and pave the way to the development of appropriate therapeutic strategies.

No MeSH data available.


Related in: MedlinePlus