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Open Access 01-12-2018 | Research article

Signaling protein signature predicts clinical outcome of non-small-cell lung cancer

Authors: Bao-Feng Jin, Fan Yang, Xiao-Min Ying, Lin Gong, Shuo-Feng Hu, Qing Zhao, Yi-Da Liao, Ke-Zhong Chen, Teng Li, Yan-Hong Tai, Yuan Cao, Xiao Li, Yan Huang, Xiao-Yan Zhan, Xuan-He Qin, Jin Wu, Shuai Chen, Sai-Sai Guo, Yu-Cheng Zhang, Jing Chen, Dan-Hua Shen, Kun-Kun Sun, Lu Chen, Wei-Hua Li, Ai-Ling Li, Na Wang, Qing Xia, Jun Wang, Tao Zhou

Published in: BMC Cancer | Issue 1/2018

Abstract

Background

Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application.

Methods

A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort.

Results

A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P < 0.001) and SCC patients (27 months vs. not reached, HR 9.97; P < 0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018).

Conclusions

Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.

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Title: Signaling protein signature predicts clinical outcome of non-small-cell lung cancer
Authors: Bao-Feng Jin
Fan Yang
Xiao-Min Ying
Lin Gong
Shuo-Feng Hu
Qing Zhao
Yi-Da Liao
Ke-Zhong Chen
Teng Li
Yan-Hong Tai
Yuan Cao
Xiao Li
Yan Huang
Xiao-Yan Zhan
Xuan-He Qin
Jin Wu
Shuai Chen
Sai-Sai Guo
Yu-Cheng Zhang
Jing Chen
Dan-Hua Shen
Kun-Kun Sun
Lu Chen
Wei-Hua Li
Ai-Ling Li
Na Wang
Qing Xia
Jun Wang
Tao Zhou
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-4104-4

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