World Journal of Surgical Oncology | |
Expression of multidrug resistance-associated proteins and their relation to postoperative individualized chemotherapy in gastric cancer | |
Ruizeng Dong1  Ling Huang1  Qiming Yu1  Xiangdong Cheng1  Yian Du1  Pengfei Yu1  | |
[1] Department of Abdominal Surgery, Zhejiang Cancer Hospital, 38# Guangji Road, Hangzhou 310022, China | |
关键词: prognosis; chemotherapy; multidrug resistance-associated proteins; stomach neoplasms; | |
Others : 1147812 DOI : 10.1186/1477-7819-12-307 |
|
received in 2014-02-12, accepted in 2014-09-25, 发布年份 2014 | |
【 摘 要 】
Background
Adjuvant chemotherapy could reduce residual tumor cells and prevent relapse, however, not all patients are suitable for adjuvant chemotherapy. Screening appropriate patients based on molecular markers for individualized adjuvant chemotherapy is necessary.
Methods
Between June 2002 and June 2004, 119 patients who underwent radical gastrectomy were retrospectively analyzed. Some patients had adjuvant chemotherapy based on platinum and 5-FU for four to six cycles. Topoisomerase II (ToPo II) negative, multidrug resistance protein (MRP) positive and glutathione S-transferase π (GST-π) positive were regarded as three risk factors that may be associated with chemotherapy resistance and poor prognosis. Patients were divided into two groups: a high-risk group (≥2 risk factors) and a low-risk group (<2 risk factors), and tumor recurrence and patient survival time of the two groups were analyzed.
Results
The average recurrence time of the low-risk group was significantly longer than that of the high-risk group (21.29 ± 11.10 versus 15.16 ± 8.05 months, P <0.01). The 3-year and 5-year survival rates of the high-risk group were 57.4% and 42.6%, however, it had no significant difference compared to 66.2% and 58.5% of the low-risk group (P >0.05). In the high-risk group, the 3-year survival rates of patients with/without chemotherapy were 62.1% and 52.0% and the 5-year survival rates were 44.8% and 40.0%, respectively, but the difference was not statistically significant (P >0.05). In the low-risk group, the 3-year survival rates of patients with/without chemotherapy were 81.2% and 51.5%, and the 5-year survival rates were 71.9% and 45.5%, respectively, these differences were statistically significant (P <0.05).
Conclusions
Combined detection of the multidrug resistance (MDR)-related proteins ToPo II, MRP and GST-π may be prospectively valuable for postoperative individualized chemotherapy and in further predicting the outcomes of gastric cancer patients.
【 授权许可】
2014 Yu et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150404044646723.pdf | 605KB | download | |
Figure 3. | 24KB | Image | download |
Figure 2. | 25KB | Image | download |
Figure 1. | 97KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Kodera Y, Ito S, Mochizuki Y, Kondo K, Koshikawa K, Suzuki N, Kojima H, Kojima T, Matsui T, Takase T, Tsuboi K, Fujiwara M, Nakao A: A phase II study of radical surgery followed by postoperative chemotherapy with S-1 for gastric carcinoma with free cancer cells in the peritoneal cavity (CCOG0301 study). Eur J Surg Oncol 2009, 35:1158-1163.
- [2]Omura T, Shimada Y, Nagata T, Okumura T, Fukuoka J, Yamagishi F, Tajika S, Nakajima S, Kawabe A, Tsukada K: Relapse-associated microRNA in gastric cancer patients after S-1 adjuvant chemotherapy. Oncol Rep 2014, 31:613-618.
- [3]Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F: Noh SH; CLASSIC trial investigators: Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 2012, 379:315-321.
- [4]Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y: Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol 2012, 29:4387-4393.
- [5]Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J: Kang YK; ToGA Trial Investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2012, 376:687-697.
- [6]Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, Zhang S, Lee M, Wu J, Lim KH, Lei Z, Goh G, Lim QY, Tan AL, Sin Poh DY, Riahi S, Bell S, Shi MM, Linnartz R, Zhu F, Yeoh KG, Toh HC, Yong WP, Cheong HC, Rha SY, Boussioutas A, Grabsch H, Rozen S, Tan P: A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 2012, 61:673-684.
- [7]Liu Y, Chen J, Shao N, Feng Y, Wang Y, Zhang L: Clinical value of hematologic test in predicting tumor response to neoadjuvant chemotherapy with esophageal squamous cell carcinoma. World J Surg Oncol 2014, 12:43. BioMed Central Full Text
- [8]Lu D, Shi HC, Wang ZX, Gu XW, Zeng YJ: Multidrug resistance-associated biomarkers PGP, GST-pi, Topo-II and LRP as prognostic factors in primary ovarian carcinoma. Br J Biomed Sci 2011, 68:69-74.
- [9]Kunjachan S, Rychlik B, Storm G, Kiessling F, Lammers T: Multidrug resistance: Physiological principles and nanomedical solutions. Adv Drug Deliv Rev 2013, 65:1852-1865.
- [10]Shi H, Lu D, Shu Y, Shi W, Lu S, Wang K: Expression of multidrug resistance-related proteins P-glycoproteinglutathione-s-transferases, ToPoisomerase-II and Lung resistance protein in primary gastric cardiac adenocarcinoma. Cancer Invest 2008, 26:344-351.
- [11]Wu Y, Wei ZW, He YL, Schwarz RE, Smith DD, Xia GK, Zhang CH: Efficacy of adjuvant XELOX and FOLFOX6 chemotherapy after D2 dissection for gastric cancer. World J Gastroenterol 2013, 19:3309-3315.
- [12]Fujitani K: Overview of adjuvant and neoadjuvant therapy for resectable gastric cancer in the East. Dig Surg 2013, 30:119-129.
- [13]Li Y, Tan BB, Zhao Q, Fan LQ, Liu Y, Hao YJ, Zhao XF: Tumor chemosensitivity is correlated with expression of multidrug resistance associated factors in variously differentiated gastric carcinoma tissues. Hepatogastroenterology 2013, 60:213-216.
- [14]Zhu CY, Lv YP, Yan DF, Gao FL: Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells. Asian Pac J Cancer Prev 2013, 14:6757-6760.
- [15]Xu HW, Xu L, Hao JH, Qin CY, Liu H: Expression of P-glycoprotein and multidrug resistance-associated protein is associated with multidrug resistance in gastric cancer. J Int Med Res 2010, 38:34-42.
- [16]Ge J, Chen Z, Wu S, Chen J, Li X, Li J, Yin J, Chen Z: Expression levels of insulin-like growth factor-1 and multidrug resistance-associated protein-1 indicate poor prognosis in patients with gastric cancer. Digestion 2009, 80:148-158.
- [17]Soh Y, Goto S, Kitajima M, Moriyama S, Kotera K, Nakayama T, Nakajima H, Kondo T, Ishimaru T: Nuclear localisation of glutathione S-transferase pi is an evaluation factor for drug resistance in gynaecological cancers. Clin Oncol (R Coll Radiol) 2005, 17:264-270.
- [18]Gate L, Majumdar RS, Lunk A, Tew KD: Influence of glutathione S-transferase pi and p53 expression on tumor frequency and spectrum in mice. Int J Cancer 2005, 113:29-35.
- [19]Chen W, Qiu J, Shen YM: Topoisomerase IIα, rather than IIβ, is a promising target in development of anti-cancer drugs. Drug Discov Ther 2012, 6:230-237.
- [20]Chau M, Christensen JL, Ajami AM, Capizzi RL: Amonafide, a topoisomerase II inhibitor, is unaffected by P-glycoprotein-mediated efflux. Leuk Res 2008, 32:465-473.
- [21]Cao DY, Shen K, Yang JX, Guan J: The expression of MRP, GST-pi, Topo IIalpha and COX-2 in epithelial ovarian cancer and its relationship to drug resistance and prognosis. Zhonghua Yi Xue Za Zhi 2007, 87:1738-1741.