A prognostic mRNA expression signature of four 16q24.3 genes in radio(chemo)therapy‐treated head and neck squamous cell carcinoma (HNSCC)

Abstract

Previously, we have shown that copy number gain of the chromosomal band 16q24.3 is associated with impaired clinical outcome of radiotherapy‐treated head and neck squamous cell carcinoma (HNSCC) patients. We set out to identify a prognostic mRNA signature from genes located on 16q24.3 in radio(chemo)therapy‐treated HNSCC patients of the TCGA (The Cancer Genome Atlas, n = 99) cohort. We applied stepwise forward selection using expression data of 41 16q24.3 genes. The resulting optimal Cox‐proportional hazards regression model included the genes APRT, CENPBD1, CHMP1A, and GALNS. Afterward, the prognostic value of the classifier was confirmed in an independent cohort of HNSCC patients treated by adjuvant radio(chemo)therapy (LMU‐KKG cohort). The signature significantly differentiated high‐ and low‐risk patients with regard to overall survival (HR = 2.01, 95% CI 1.10–3.70; P = 0.02125), recurrence‐free survival (HR = 1.84, 95% CI 1.01–3.34; P = 0.04206), and locoregional recurrence‐free survival (HR = 1.87, 95% CI 1.03–3.40; P = 0.03641). The functional impact of the four signature genes was investigated after reconstruction of a gene association network from transcriptome data of the TCGA HNSCC cohort using a partial correlation approach. Subsequent pathway enrichment analysis of the network neighborhood (first and second) of the signature genes suggests involvement of HNSCC‐associated signaling pathways such as apoptosis, cell cycle, cell adhesion, EGFR, JAK‐STAT, and mTOR. Furthermore, a detailed analysis of the first neighborhood revealed a cluster of co‐expressed genes located on chromosome 16q, substantiating the impact of 16q24.3 alterations in poor clinical outcome of HNSCC. The reported gene expression signature represents a prognostic marker in HNSCC patients following postoperative radio(chemo)therapy.

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

“…Deletions in 16q24.2 have been observed frequently in patients with KBG syndrome [33,34], autism spectrum disorder, intellectual disability and congenital renal malformation [30]. Moreover, 16q24.3 alterations aggravate the clinical outcomes of head and neck squamous cell carcinoma [35]. The other RPL-associated CNV identified in this study was duplication of 16p13.3 (7.9 Mb), which was found in 18 cases of miscarriage, but not in the SA cases group.…”

Transcriptome sequencing analysis of mono‑ADP‑ribosylation in colorectal cancer cells

“…Based on this, it was shown that the histone variants HIST2H3PS2, HIST2H3D, HIST1H2AI and CENPBD1 were significantly differentially expressed In eukaryotes, the existence of histone variants is based on differences in the primary amino acid sequences, and these variants have different regulatory mechanisms of expression, deposition and genome occupancy (33). Histone variants can alter the structure of nucleosomes and participate in the transcription, replication and repair of DNA (47). CENPBD1 contributes to the formation of the centromere, and may be associated with the prognosis of head and neck squamous cell carcinoma (48).…”

Digital scoring of EpCAM and slug expression as prognostic markers in head and neck squamous cell carcinomas

“…Tumor stage was assessed using the UICC TNM Classification of Malignant Tumors, 7th edition. HPV status of the patients was determined by p16 INK4a immunohistochemistry in combination with HPV DNA detection as described before [24]. Age, sex, tumor localization, TNM, perineural invasion, extracapsular extension, grading, UICC staging, and HPV status of all patients are provided in Table 1.…”