Abstract 3442: Genome-wide association study reveals potential biomarkers after pulmonary metastasectomy for head and neck cancer
Authors: Hsueh-Ju Lu, Chih-Cheng Hsieh, Chi-Chun Yeh, Yi-Chen Yeh, Muh-Hwa Yang, Chi-Ying F. Huang, Peter Mu-Hsin Chang
Journal: Cancer Research (2018)

Abstract Introduction: At least 10% of head neck cancer squamous cell carcinoma (HNSCC) progress to pulmonary metastases with overall survival (OS) around 12 months. Whether aggressively pulmonary metastasectomy (PM) improving survival or not is controversial. Method and materials: Different head neck cancer patients receiving PM from thoracic surgeon were enrolled from 2003 to 2012. Matched HNSCC and adenoid cystic carcinoma (ACC) samples as control were selected to perform whole-exon sequencing (WES) and identify potential biomarkers between short- and long- term surviving groups after metastasectomy. Identified mutant genes were mapped into possible signaling pathways by using DAVID ( https://david.ncifcrf.gov/). Result: A total of 31 head and neck cancer patients were enrolled and the survivals were different significantly among cancer types. Eight matched PM samples (3 short-term post-metastaectomy survival (PMS) HNSCC, 3 long-term HNSCC, and 2 ACC), with differently clinical outcomes (PMS, P = 0.016; OS, P = 0.015), were enrolled for WES. Eighteen percentages (18%, 306/1706) of identified genetic alternations were mapped into DAVID. Cancer-associated signal pathways were top-ranked related to short-term HNSCC; hematopoietic cell lineage associated pathways for long-term HNSCC; complement and coagulation cascades associated pathways for ACC. The overlapped genes between short-term HNSCC and ACC were relative to metabolic-associated pathway, such as branched-chain amino acid consumption (P &amp;lt; 0.001, fold enrichment (FE) = 7.97) and the metabolism of arginine and proline metabolism (P &amp;lt; 0.001, FE = 4.96). The overlapped genes between long-term HNSCC and ACC were relative to focal adhesion (P =0.008, FE = 2.84) and ECM-receptor interaction (P = 0.015, FE = 4.08). Conclusion: Genome-wide association study effectively separated clinical outcome of head neck cancer patients and successfully identified specific mutations for prognosis after PM. Basic characteristics of patients receiving whole-exon sequencing for pulmonary metastatic tumor.GroupAgeGenderPrimary tumor siteHistological typeInitial pathologic stagingBrief historyOverall survivalPost-metastasectomy survivalCase 1Short-term survival86.0MaleHypopharynxSquamous cell carcinomapT4aN2bSurgical resection followed by adjuvant radiotherapy; one metastatic nodule at right lower lung was resected.23.914.4Case 2Short-term survival60.9MaleOropharynxSquamous cell carcinomapT4aN1Surgical resection followed by adjuvant chemoradiotherapy; two metastatic nodules at right and left upper lung were resected.26.011.9Case 3Short-term survival47.1MaleOropharynxSquamous cell carcinomapT4aN2bInduction chemotherapy followed by definitive surgical resection and adjuvant chemoradiotherapy; one left upper lung metastasis was resected.22.87.1Case 4Long-term survival38.9MaleHypopharynxSquamous cell carcinomapT2N2bSurgical resection followed by adjuvant radiotherapy; multiple bilateral lung metastases with sequential wedge resection for left and right side lesions52.140.2Case 5Long-term survival51.3MaleHypopharynxSquamous cell carcinomapT3N2bSurgical resection followed by adjuvant chemoradiotherapy; 3 metastatic lesion at right upper, middle and left lower lung were resected.89.842.7Case 6Long-term survival54.4MaleHypopharynxSquamous cell carcinomapT4aN2bSurgical resection followed by adjuvant chemoradiotherapy; 2 metastatic lesions at bilateral lung apices with sequential wedge resection134.891.1Case 7Control39.6FemaleOral cavityAdenoid cystic carcinomapT4aNoSurgical resection followed by adjuvant chemoradiotherapy; 2 metastatic nodules at right upper and middle lung were resected130.187.0Case 8Control46.2FemaleRight maxillary sinus and nasal cavityAdenoid cystic carcinomaUnknownSurgical resection followed by adjuvant radiotherapy; 2 metastatic nodules at right upper and middle lung were resected195.079.9 Citation Format: Hsueh-Ju Lu, Chih-Cheng Hsieh, Chi-Chun Yeh, Yi-Chen Yeh, Muh-Hwa Yang, Chi-Ying F. Huang, Peter Mu-Hsin Chang. Genome-wide association study reveals potential biomarkers after pulmonary metastasectomy for head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3442.