Transcriptomic Abnormalities Associated With Recurrence And Metastasis In Laryngeal Squamous Cell Carcinomas

Objective: To explore the abnormalities associated with recurrence and metastasis in laryngeal squamous cell carcinomas (SCC), using comparative expressed sequence hybridization (CESH).Material and Methods: Total RNA was isolated from the tumor tissue derived from 27 cases of laryngeal SCC and placenta tissues. A cytogenetic approach, CESH that is based on comparative genetic hybridization (CGH), was applied to detect the chromosomal regions harboring abnormally expressed genes over the transcriptome. The resulting chromosome regions were then analyzed on their correlations with local recurrence, metastasis of and other pathological features. Four genes (RFC5, ARK5, TTXNRD1 and I-Plastin) derived from the 'over-expressed chromosome regions' were investigated in another 20 paired laryngeal SCC tumor tissues and their corresponding normal mucosas by RT-PCR.Results: (1) Among the 27 cases of laryngeal SCC, 378 abnormally expressed chromosomal regions were detected, including 280 over-expressing and 98 under-expressing regions. The most frequently overexpressed chromosome regions were 22q12-q13.2(63.0%), 12q11-q14 (63.0%), 9q22-q33(55.6%), 11q12-q21(55.6%), 16p12-pl3(55.6%), 7q21-q33(51.9%), and 1p32-p36(51.9%), while the most frequently under-expressed regions were Yq (66.7%, male), 18q22-q23(48.1%), 3p23-pter(29.6%), and 13q22-qter (29.6%). (2) Overexpression of 1q21-q32, 3q13.3-q27 and 11p13-p15.3 are associated with metastasis of laryngeal SCC. Up-regulated expression of 7p15.3-p21, 11q12-q21 may also correlate with metastasis. (3) Overexpression of 1q21-q32, 3q13.3-q27, 10q22-q25, 22q12-q13.2 and under-expression of 3p22-pter are associated with local recurrence of laryngeal SCC. Up-regulated expression of 12p12-p13 and down-regulated expression of 13q22-qter may also correlate with recurrence. (4) The differences of abnormal expression of 9p22-pter, 13q31-q34 and 4q31.3-q34...