Chromosomal instability as a prognostic marker in cervical cancer.

Christine How,Fei-Fei Liu,Benjamin Haibe-Kains,Jonathan So,David W Hedley,Melania Pintilie,Anthony Fyles,Richard P Hill,Blaise A Clarke,Angela Hui,Michael Milosevic,Jeff Bruce

doi:10.1186/s12885-015-1372-0

Christine How, Fei-Fei Liu + Show 10 more

Open Access

https://doi.org/10.1186/s12885-015-1372-0

Copy DOI

Abstract

BackgroundCervical cancer is the third most common cancer in women globally, and despite treatment, distant metastasis and nodal recurrence will still develop in approximately 30% of patients. The ability to predict which patients are likely to experience distant relapse would allow clinicians to better tailor treatment. Previous studies have investigated the role of chromosomal instability (CIN) in cancer, which can promote tumour initiation and growth; a hallmark of human malignancies. In this study, we sought to examine the published CIN70 gene signature in a cohort of cervical cancer patients treated at the Princess Margaret (PM) Cancer Centre and an independent cohort of The Cancer Genome Atlas (TCGA) cervical cancer patients, to determine if this CIN signature associated with patient outcome.MethodsCervical cancer samples were collected from 79 patients, treated between 2000–2007 at the PM, prior to undergoing curative chemo-radiation. Total RNA was extracted from each patient sample and analyzed using the GeneChip Human Genome U133 Plus 2.0 array (Affymetrix).ResultsHigh CIN70 scores were significantly related to increased chromosomal alterations in TCGA cervical cancer patients, including a higher percentage of genome altered and a higher number of copy number alterations. In addition, this same CIN70 signature was shown to be predictive of para-aortic nodal relapse in the PM Cancer Centre cohort.ConclusionsThese findings demonstrate that chromosomal instability plays an important role in cervical cancer, and is significantly associated with patient outcome. For the first time, this CIN70 gene signature provided prognostic value for patients with cervical cancer.

Highlights

Cervical cancer is the third most common cancer in women globally, and despite treatment, distant metastasis and nodal recurrence will still develop in approximately 30% of patients
Princess Margaret (PM) and The Cancer Genome Atlas (TCGA) cohorts showed a distinct expression pattern of CIN70 genes according to CIN70 score The clinical characteristics of the 79 PM Cancer Centre and 130 TCGA patients are shown in Tables 1 and 2, respectively
Our study further extended the application of this CIN70 signature to cervical cancer

Summary

Introduction

Cervical cancer is the third most common cancer in women globally, and despite treatment, distant metastasis and nodal recurrence will still develop in approximately 30% of patients. Previous studies have investigated the role of chromosomal instability (CIN) in cancer, which can promote tumour initiation and growth; a hallmark of human malignancies. Using a computational approach to identify specific genes whose expression was consistently correlated with total functional aneuploidy across multiple cancer types, Carter et al developed a gene expression signature of CIN, the CIN70, which could predict patient survival and prognosis [14]. Over-expression of this CIN70 signature was predictive of poor clinical outcome in 12 datasets representing six types of tumour: lymphoma, lung adenocarcinoma, glioma, medulloblastoma, mesothelioma, and breast cancer [15,16,17,18,19,20,21,22,23,24,25,26]. We sought to examine CIN in cervical cancer and determine

Methods

Results

Discussion

Conclusion