Prediction of radiosensitive patients with gastric cancer by developing gene signature

Zhou,Jin; Wu,Xiaoyu; Li,Gang; Gao,Xin; Zhai,Min; Chen,Weichang; Hu,Huagang; Tang,Zaixiang

doi:10.3892/ijo.2017.4107

Prediction of radiosensitive patients with gastric cancer by developing gene signature

Authors:
- Jin Zhou
- Xiaoyu Wu
- Gang Li
- Xin Gao
- Min Zhai
- Weichang Chen
- Huagang Hu
- Zaixiang Tang
View Affiliations

Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China, Department of General Surgery, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, School of Nursing, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, and Center for Genetic Epidemiology and Genomics, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
Published online on: August 30, 2017 https://doi.org/10.3892/ijo.2017.4107
Pages: 1067-1076
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Adjuvant radiotherapy is an important clinical treatment for the majority of gastric cancer, a common cancer. However, radiotherapy is a double-edged sword. It is necessary to develop a method to predict radiosensitive patients who are most likely to benefit from radiotherapy. Using the publicly available data of gastric cancer from The Cancer Genome Atlas (TCGA), we developed a gene signature that predicts radiosensitive patients through estimating a new index, nominal HR (nHR) (HR product of sensitive genes), for each patient. In this study, we provided several results to validate our prediction. Cross-validation results showed that the predicted radiosensitive patients who received radiotherapy had significantly better survival than predicted radiosensitive patients who did not receive radiotherapy. After adjusting for other clinical factors, including age, sex, target therapy, histologic diagnosis, tumor stage, the benefit of radiotherapy on predicted radiosensitive patient remained significant. In addition, predicted radiosensitive patients who received radiotherapy had a significantly reduced rate of disease progression. Taken together, we have obtained a set of genes, to identify radiosensitive patients with gastric cancer. These genes may be potential biomarkers for diagnosis and treatment of gastric cancer, which could give new insight for revealing the underlying mechanism of radiosensitivity of gastric cancer.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
3	Ajani JA, D'Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, Denlinger CS, Fanta P, Farjah F, Fuchs CS, et al: Gastric cancer, version 3.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 14:1286–1312. 2016. View Article : Google Scholar : PubMed/NCBI
4	Zhang ZX, Gu XZ, Yin WB, Huang GJ, Zhang DW and Zhang RG: Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC) - report on 370 patients. Int J Radiat Oncol Biol Phys. 42:929–934. 1998. View Article : Google Scholar : PubMed/NCBI
5	Hazard L, O'Connor J and Scaife C: Role of radiation therapy in gastric adenocarcinoma. World J Gastroenterol. 12:1511–1520. 2006. View Article : Google Scholar : PubMed/NCBI
6	Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, et al: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 345:725–730. 2001. View Article : Google Scholar : PubMed/NCBI
7	Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, et al: Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: The ARTIST trial. J Clin Oncol. 30:268–273. 2012. View Article : Google Scholar
8	Minn AY, Hsu A, La T, Kunz P, Fisher GA, Ford JM, Norton JA, Visser B, Goodman KA, Koong AC, et al: Comparison of intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy as adjuvant therapy for gastric cancer. Cancer. 116:3943–3952. 2010. View Article : Google Scholar : PubMed/NCBI
9	Freidlin B, Jiang W and Simon R: The cross-validated adaptive signature design. Clin Cancer Res. 16:691–698. 2010. View Article : Google Scholar : PubMed/NCBI
10	Freidlin B and Simon R: Adaptive signature design: an adaptive clinical trial design for generating and prospectively testing a gene expression signature for sensitive patients. Clin Cancer Res. 11:7872–7878. 2005. View Article : Google Scholar : PubMed/NCBI
11	Tang Z, Zeng Q, Li Y, Zhang X, Ma J, Suto MJ, Xu B and Yi N: Development of a radiosensitivity gene signature for patients with soft tissue sarcoma. Oncotarget. 8:27428–27439. 2017.PubMed/NCBI
12	Molinaro AM, Simon R and Pfeiffer RM: Prediction error estimation: A comparison of resampling methods. Bioinformatics. 21:3301–3307. 2005. View Article : Google Scholar : PubMed/NCBI
13	Moertel CG, Childs DS Jr, Reitemeier RJ, Colby MY Jr and Holbrook MA: Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 2:865–867. 1969. View Article : Google Scholar : PubMed/NCBI
14	Lowy AM, Feig BW, Janjan N, Rich TA, Pisters PW, Ajani JA and Mansfield PF: A pilot study of preoperative chemoradiotherapy for resectable gastric cancer. Ann Surg Oncol. 8:519–524. 2001. View Article : Google Scholar : PubMed/NCBI
15	Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, et al German Rectal Cancer Study Group: Preoperative chemo-radiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: Initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 13:679–687. 2012. View Article : Google Scholar
16	Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, et al: Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): An open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 15:1245–1253. 2014. View Article : Google Scholar : PubMed/NCBI
17	Dikken JL, Jansen EP, Cats A, Bakker B, Hartgrink HH, Kranenbarg EM, Boot H, Putter H, Peeters KC, van de Velde CJ, et al: Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer. J Clin Oncol. 28:2430–2436. 2010. View Article : Google Scholar : PubMed/NCBI
18	Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, et al: Updated analysis of SWOG-directed intergroup study 0116: A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 30:2327–2333. 2012. View Article : Google Scholar : PubMed/NCBI
19	Liu GF, Bair RJ, Bair E, Liauw SL and Koshy M: Clinical outcomes for gastric cancer following adjuvant chemoradiation utilizing intensity modulated versus three-dimensional conformal radiotherapy. PLoS One. 9:e826422014. View Article : Google Scholar : PubMed/NCBI
20	Wang X, Li G, Zhang Y, Bai S, Xu F, Wei Y and Gong Y: Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). Med Dosim. 38:395–400. 2013. View Article : Google Scholar : PubMed/NCBI
21	Dahele M, Skinner M, Schultz B, Cardoso M, Bell C and Ung YC: Adjuvant radiotherapy for gastric cancer: A dosimetric comparison of 3-dimensional conformal radiotherapy, tomotherapy and conventional intensity modulated radiotherapy treatment plans. Med Dosim. 35:115–121. 2010. View Article : Google Scholar
22	Jameson JL and Longo DL: Precision medicine - personalized, problematic, and promising. N Engl J Med. 372:2229–2234. 2015. View Article : Google Scholar : PubMed/NCBI
23	Martens FK, Kers JG and Janssens AC: External validation is only needed when prediction models are worth it (Letter commenting on: J Clin Epidemiol. 2015;68:25–34). J Clin Epidemiol. 69:249–250. 2016. View Article : Google Scholar
24	Bleeker SE, Moll HA, Steyerberg EW, Donders AR, Derksen-Lubsen G, Grobbee DE and Moons KG: External validation is necessary in prediction research: A clinical example. J Clin Epidemiol. 56:826–832. 2003. View Article : Google Scholar : PubMed/NCBI
25	Bijlsma MW, Brouwer MC, Bossuyt PM, Heymans MW, van der Ende A, Tanck MW and van de Beek D: Risk scores for outcome in bacterial meningitis: Systematic review and external validation study. J Infect. 73:393–401. 2016. View Article : Google Scholar : PubMed/NCBI
26	Wang J, Chen C, Li HF, Jiang XL and Zhang L: Investigating key genes associated with ovarian cancer by integrating affinity propagation clustering and mutual information network analysis. Eur Rev Med Pharmacol Sci. 20:2532–2540. 2016.PubMed/NCBI