Gene‑expression signature predicts survival benefit from postoperative chemoradiotherapy in head and neck squamous cell carcinoma

Jin, Chen; Fu, Guiming; Chen, Yibo; Zhu, Guiquan; Wang, Zhaohui

doi:10.3892/ol.2018.8964

Cited by 7 publications

(5 citation statements)

References 27 publications

(30 reference statements)

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“…Higher FOS expression is associated with a better outcome in breast cancer datasets (24). Using public data from TCGA, a 22-gene signature that demonstrated the best predictive value for assessing the clinical benefit of postoperative chemoradiotherapy was established (25).…”

Section: Discussionmentioning

confidence: 99%

CPSF3 is a promising prognostic biomarker and predicts recurrence of non‑small cell lung cancer

et al. 2019

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Cleavage polyadenylation specificity factor (CPSF) is the core component of the 3′-end processing complex, which determines the site of 3′-end cleavage interactions of specific sequence elements within pre-mRNAs. The present study revealed that all members of the CPSF complex were overexpressed in lung cancer tissue from The Cancer Genome Atlas (TCGA) Lung Cancer Cohort compared with normal lung tissue. Analysis of overall survival and recurrence-free survival verified that only CPSF3 was associated with prognosis and recurrence of lung adenocarcinoma (LUAD), and thus could be a promising biomarker. Additionally, receiver operating characteristic curve analysis revealed that CPSF3 may function as a diagnostic biomarker to distinguish between two histological subtypes of non-small cell lung cancer. Furthermore, analysis of the association of CPSF3 expression with clinicopathological parameters indicated that CPSF3 was associated with smoking history, tumor diameter, lymph node metastasis, clinical stage and radiation therapy in LUAD. Additionally, analysis of the DNA methylation data of the TCGA-LUAD Cohort revealed that CPSF3 DNA CpG sites (cg12057242 and cg25739938) were generally hypomethylated in LUAD compared with normal lung tissue. Correlation analysis identified the CPSF3 DNA CpG site cg25739938 to be negatively correlated with CPSF3 expression, while no correlation was identified with cg12057242. In addition, correlation analysis demonstrated that the overexpression of CPSF3 was correlated with CPSF3 DNA copy number variants (CNAs). The findings indicate that abnormal expression of CPSF3 may be caused by DNA CNAs; and DNA hypermethylation and function may be a promising diagnostic and prognostic indicator for LUAD.

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Section: Discussionmentioning

confidence: 99%

CPSF3 is a promising prognostic biomarker and predicts recurrence of non‑small cell lung cancer

et al. 2019

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“…On the basis of differentially enriched gene sets between primary and relapsed tumors, we obtained deregulated pathways and cellular functions in tumor recurrences and individual transcriptional subtypes. Next, we selected published sets of metagenes from prognostic signatures that are related to the GSEA related functions and important prognostic features: HYPOXIA, RADIATION RESISTANCE, P-EMT, EGFR, SURVIVAL, TUMOR INFLAMMATION SIGNATURE (TIS) (9,(32)(33)(34)(35).…”

Section: Tumor Recurrence and Transcriptional Subtypes Associated Wit...mentioning

confidence: 99%

Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer

Weber

Künstner

Heß

et al. 2022

Clinical Cancer Research

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Purpose: The genetic relatedness between primary and recurrent head and neck squamous cell carcinomas (HNSCC) reflects the extent of heterogeneity and therapy-driven selection of tumor subpopulations. Yet, current treatment of recurrent HNSCC ignores the molecular characteristics of therapy-resistant tumor populations. Experimental Design: From 150 tumors, 74 primary HNSCCs were RNA sequenced and 38 matched primary/recurrent tumor pairs were both whole-exome and RNA sequenced. Transcriptome analysis determined the predominant classical (CL), basal (BA), and inflamed-mesenchymal (IMS) transcriptional subtypes according to an established classification. Genomic alterations and clonal compositions of tumors were evaluated from whole-exome data. Results: Although CL and IMS subtypes were more common in primary HNSCC with low recurrence rates, the BA subtype was more prevalent and stable in recurrent tumors. The BA subtype was associated with a transcriptional signature of partial epithelial-to-mesenchymal transition (p-EMT) and early recurrence. In 44% of matched cases, the dominant subtype changed from primary to recurrent tumors, preferably from IMS to BA or CL. Expression analysis of prognostic gene sets identified upregulation of hypoxia, p-emt, and radiotherapy resistance signatures and downregulation of tumor inflammation in recurrences compared with index tumors. A relevant subset of primary/recurrent tumor pairs presented no evidence for a common clonal origin. Conclusions: Our study showed a high degree of genetic and transcriptional heterogeneity between primary/recurrent tumors, suggesting therapy-related selection of a transcriptional subtype with characteristics unfavorable for therapy. We conclude that therapy decisions should be based on genetic and transcriptional characteristics of recurrences rather than primary tumors to enable optimally tailored treatment strategies.

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“…Some studies have also suggested a predictive role of p16 expression for the treatment with chemoradiotherapy or EGFR-inhibitors [ 44 , 45 , 46 ]. In the SPECTRUM and the LUX-H&N1 trial p16 positivity was associated with reduced benefit from the addition of panitumumab to chemotherapy and afatinib compared to methotrexate [ 45 , 46 ].…”

Section: Hpv Infection and P16mentioning

confidence: 99%

Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma

Magnes

Wagner

Kiem

et al. 2021

IJMS

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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosa of the upper aerodigestive tract. Despite multimodality treatments approximately half of all patients with locally advanced disease relapse and the prognosis of patients with recurrent or metastatic HNSCC is dismal. The introduction of checkpoint inhibitors improved the treatment options for these patients and pembrolizumab alone or in combination with a platinum and fluorouracil is now the standard of care for first-line therapy. However, approximately only one third of unselected patients respond to this combination and the response rate to checkpoint inhibitors alone is even lower. This shows that there is an urgent need to improve prognostication and prediction of treatment benefits in patients with HNSCC. In this review, we summarize the most relevant risk factors in the field and discuss their roles and limitations. The human papilloma virus (HPV) status for patients with oropharyngeal cancer and the combined positive score are the only biomarkers consistently used in clinical routine. Other factors, such as the tumor mutational burden and the immune microenvironment have been highly studied and are promising but need validation in prospective trials.

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Gene‑expression signature predicts survival benefit from postoperative chemoradiotherapy in head and neck squamous cell carcinoma

Cited by 7 publications

References 27 publications

CPSF3 is a promising prognostic biomarker and predicts recurrence of non‑small cell lung cancer

CPSF3 is a promising prognostic biomarker and predicts recurrence of non‑small cell lung cancer

Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer

Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma

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