Development of a radiosensitivity gene signature for patients with soft tissue sarcoma

Abstract

Adjuvant radiotherapy is an important clinical treatment option for the majority of sarcomas. The motivation of current study is to identify a gene signature and to predict radiosensitive patients who are most likely to benefit from radiotherapy. Using the public available data of soft tissue sarcoma from The Cancer Genome Atlas, we developed a cross-validation procedure for identifying a gene signature and predicting radiosensitive patients through. The result showed that the predicted radiosensitive patients who received radiotherapy had a significantly better survival with a reduced rate of new tumor event and disease progression. Strata analysis showed that the predicted radiosensitive patients had significantly better survival under radiotherapy independent of histologic types. A hierarchical cluster analysis was used to validate the gene signature, and the results showed the predicted sensitivity for each patient well matched the results from cluster analysis. Together, we demonstrate a radiosensitive molecular signature that can be potentially used for identifying radiosensitive patients with sarcoma.

Developing a radiosensitivity gene signature for Caucasian patients with breast cancer

“…A nested inner loop of the K-fold cross-validation approach can be used on the training data to select the best tuning parameter values without affecting the statistical validity of the procedure. Similar procedures for the two key tuning parameters (25) and for more tuning parameters have also been reported in previous studies (23,24).…”

“…Although the adaptive method was proposed and used in previous studies (25,35,36), the procedure in the Training step was further updated in the present study. Only significant genes with negative interaction effects were selected for further prediction.…”

“…Freidlin and Simon (24) in 2005 and Freidlin et al (23) in 2010 developed a novel cross-validated adaptive signature design to identify sensitive patients in clinical trial for binary outcome. Following the framework of these studies, this approach was modified and extended to the proportional hazards model, and used to develop radiosensitive gene signature for sarcoma data in a previous study (25). In the present study, the procedure was further improved.…”

“…Furthermore, due to the difficulty of collecting clinical samples and the large number of potential genes available for analysis, the development of a reliable diagnostic classifier using early nonrandomized phase II data is often not feasible. To overcome these difficulties, an internal cross-validation was performed via the cross-validated adaptive signature design that combined the gene signature development and the validation test in a single trial, as originally introduced by Freidlin et al (23), Freidlin and Simon (24), and Tang et al (25). The previous procedure of selecting informative genes was improved in the present study, and this novel approach was extended to the proportional hazard model.…”

Molecular radiosensitization of soft tissue sarcoma by oncolytic virus-mediated MCL1 ablation

“…In addition, radiotherapy has the potential to cause secondary cancers in irradiated tissues [4]. Therefore, radiosensitizing approaches are required to reduce the dosage of ionizing radiation delivered to STS patients, especially in certain histological subtypes where the response to radiotherapy is known to be limited [5]. STS can be divided into distinct histological subtypes, namely brosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing sarcoma, and synovial sarcoma [6].…”