Gene Expression Profiling of Advanced Penile Squamous Cell Carcinoma Receiving Cisplatin-based Chemotherapy Improves Prognostication and Identifies Potential Therapeutic Targets.
In men with advanced penile squamous cell carcinoma receiving first-line chemotherapy, visceral metastases (VM) and Eastern Cooperative Oncology Group performance status ≥1 are poor prognostic factors for overall survival (OS). We hypothesized that tumor gene expression profiling may enhance prognostic stratification and identify potential therapeutic targets. In this retrospective study, RNA extracted from macrodissected tumors underwent profiling for the expression of 738 genes using NanoString. Univariate and multivariate analyses assessed the association of genes, VM, and performance status with OS. Tumors were available from 25 men who received first-line cisplatin-based chemotherapy. In univariate analysis, upregulated MAML2 (p=0.004), KITLG (p≤0.0001), and JAK1 (p=0.029) genes were associated with poor OS, and upregulated FANCA was associated with better OS (p=0.024). In stepwise multivariate analyses, VM (hazard ratio=12.75, p=0.0001) and MAML2 (hazard ratio=10.411, p=0.003) were associated with poor OS. The presence of none, one, and both of these poor risk factors was associated with significantly different median OS of 18.4 mo, 7.2 mo, and 2.1 mo, respectively. Unsupervised clustering demonstrated two major molecular subtypes with trend for different survivals (p=0.052). Validation of results is necessary. PATIENT SUMMARY: The expression of the MAML2 gene in penile cancers from men receiving first-line cisplatin-based chemotherapy predicted overall survival independent of clinical factors.
['Necchi|Andrea|A|', 'Eigl|Bernhard J|BJ|', 'Yang|Eddy Shih-Hsin|ES|', 'Bae|Sejong|S|', 'Chandrashekar|Darshan|D|', 'Chen|Dongquan|D|', 'Naik|Gurudatta|G|', 'Mehta|Amitkumar|A|', 'Giannatempo|Patrizia|P|', 'Colecchia|Maurizio|M|', 'Gordetsky|Jennifer|J|', 'Wei|Shi|S|', 'Cooper|Tiffiny|T|', 'Varambally|Sooryanarayana|S|', 'Sonpavde|Guru|G|']
D000368:Aged D000971:Antineoplastic Combined Chemotherapy Protocols D002294:Carcinoma, Squamous Cell D002945:Cisplatin D020869:Gene Expression Profiling D006801:Humans D017567:Karnofsky Performance Status D008297:Male D008875:Middle Aged D009362:Neoplasm Metastasis D009367:Neoplasm Staging D009369:Neoplasms D010412:Penile Neoplasms D011379:Prognosis D012313:RNA D012189:Retrospective Studies D012307:Risk Factors D016019:Survival Analysis
Gene expression Advanced Penile squamous cell carcinoma Cisplatin Prognosis