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MACE sequencing of the preoperative INVERT cohort reveals EpCAM expression as a prognostic marker in Head and neck cancer

ABSTRACT: Abstract Background The aim of this study was to identify prognostic molecular biomarkers to neoadjuvant chemoradiotherapy (nCRT) in locally advanced oral cavity cancer (LA-OCC) on a transcriptome level. Materials and methods The global transcriptome of therapy-naïve LA-OCC treated within the prospective INVERT trial by nCRT were used as a discovery cohort for massive analysis of cDNA Ends (MACE) from archived biopsy specimen (n = 17; patients received nCRT consisting of 60 Gy with concomitant platinum based chemotherapy six to eight weeks preoperatively [3]) was investigated. Potential predictive biomarkers (EpCAM and Sox2) were further verified on an independent retrospective explorative tissue microarray (TMA) cohort of tumor and matched non-tumor specimen of primarily surgically resected HNSCC patients (n = 240). The biomarker expression was associated with clinicopathological features and outcome of the patients in our explorative tumor cohort. Results Deregulated transcripts between tumor tissue of patients with complete or incomplete response to the INVERT therapy regimen in our discovery cohort were shown regarding cell cycle G1/S transition, Wnt signaling, and epithelial adhesion and differentiation. Confirmation of altered expression of EpCAM on a protein level with high EpCAM expression was associated with impaired overall survival. The prognostic relevance of elevated EpCAM expression was also confirmed using the independent explorative cohort (p = 0.044). Additional Sox2 staining correlated significantly with EpCAM expression (p < 0.001) and EpCAM might serve as a risk factor for worse overall survival in our explorative cohort (p = 0.049). However, EpCAM did not serve as an independent risk factor in this cohort. Conclusion Transcriptomic profiling of therapy-naïve LA-OCC revealed biological processes and pathways that could be associated with therapy response and impaired overall survival. By translating results into readily available daily routine biomarkers, histopathological-based EpCAM and Sox2 assessment could support prognostication of patient overall survival. Prospective trials are necessary to validate this result using tissue and liquid biopsy-based approaches.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240115 | GEO | 2025/09/30

REPOSITORIES: GEO

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Project description:Background: Neoadjuvant chemoradiotherapy (NCRT) is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies. Methods: Forty-eight candidates for NCRT were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade (TRG).Results: Both Smoothing and Hidden Markov Model (HMM) approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 7q21, 7q36, 13q12, 13q32-34, 16p13, 17p12 chromosomal regions. Conclusion: This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information about response to NCRT and help to optimize therapy in rectal cancer patients. 48 samples included in the study were analyzed on whole genome BAC arrays with the aim to characterize genomic alterations and correlate them with the tumor response to therapy. The case series was composed by 15%,81% and 4% of uT2, uT3 and uT4 tumors, respectively. At the diagnosis 56% of patients had uN0 tumors and 44% uN+. 30%,13%, 23% and 34% of patients reached/mantained respectively ypT0, ypT1, ypT2 and ypT3. With regard to response to NCRT, according to TRG criteria proposed by Dworak, two group were defined: non responders (TRG0-2= 56%) and responders (TRG3-4=44%). Clinical and pathological parameters: uT: pre-therapy stage determined by ultrasounds techniques uN: pre-therapy lymph node status determined by ultrasounds techniques ypT: pathologic stage after a neoadjuvant treatment ypN: pathologic lymph node status after a neoadjuvant treatment

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MACE sequencing of the preoperative INVERT cohort reveals EpCAM expression as a prognostic marker in Head and neck cancer

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