Relationship Between Expression of Apoptosis-related Proteins and the Efficacy of Postoperative Chemotherapy in Patients with T3 Gastric Cancer

Overview

Journal Surg Today

Specialty General Surgery

Date 2011 Dec 7

PMID 22143356

Citations 7

Authors

Shunichi Tsujitani

Hiroaki Saito

Toshiro Wakatsuki

Masahide Ikeguchi

Ken Shirabe

Masaru Morita

Yoshihiro Kakeji

Tokujiro Yano

Yoshihiko Maehara

Affiliations

Soon will be listed here.

Abstract

Purpose: We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy.

Methods: We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test.

Results: Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors.

Conclusions: The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.

Citing Articles

A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer.

Ruan T, Liu W, Tao K, Wu C Onco Targets Ther. 2020; 13:1797-1807.

PMID: 32184615 PMC: 7053652. DOI: 10.2147/OTT.S239336.

Clinical Significance of p53 Protein Expression, Beta-catenin Expression and HER2 Expression for Epstein-Barr Virus-associated Gastric Cancer.

Baek D, Kang B, Hwang S, Kim J, Seo A, Bae H Chonnam Med J. 2017; 53(2):140-146.

PMID: 28584793 PMC: 5457949. DOI: 10.4068/cmj.2017.53.2.140.

Molecular mechanisms of chemoresistance in gastric cancer.

Shi W, Gao J World J Gastrointest Oncol. 2016; 8(9):673-81.

PMID: 27672425 PMC: 5027022. DOI: 10.4251/wjgo.v8.i9.673.

The prognostic significance of p53 expression in gastric cancer: a meta-analysis.

Wei K, Jiang L, Wei Y, Wang Y, Qian X, Dai Q J Cancer Res Clin Oncol. 2014; 141(4):735-48.

PMID: 25316440 DOI: 10.1007/s00432-014-1844-7.

Research and clinical applications of molecular biomarkers in gastrointestinal carcinoma (Review).

Jiao F, Jin Z, Wang L, Wang L Biomed Rep. 2014; 1(6):819-827.

PMID: 24649035 PMC: 3917016. DOI: 10.3892/br.2013.158.

References

Gudkov A, Komarova E . The role of p53 in determining sensitivity to radiotherapy. Nat Rev Cancer. 2003; 3(2):117-29. DOI: 10.1038/nrc992. View

Wei L, Kuo M, Chen C, Chou C, Cheng W, Chang M . The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by up-regulation of Mcl-1 through a PI 3-K/Akt pathway. Oncogene. 2001; 20(41):5799-809. DOI: 10.1038/sj.onc.1204733. View

Tada M, Matsumoto R, Iggo R, Onimaru R, Shirato H, Sawamura Y . Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutations. Cancer Res. 1998; 58(9):1793-7. View

Noguchi Y, Imada T, Matsumoto A, Coit D, Brennan M . Radical surgery for gastric cancer. A review of the Japanese experience. Cancer. 1989; 64(10):2053-62. DOI: 10.1002/1097-0142(19891115)64:10<2053::aid-cncr2820641014>3.0.co;2-j. View

Otani S, Maeta M, Oka A, Hirooka Y, Tsujitani S, Ikeguchi M . Long-term survival of 5 years following initial surgery for gastric cancer and simultaneous disseminated peritoneal metastasis: report of a case. Surg Today. 1995; 25(11):959-61. DOI: 10.1007/BF00312381. View

Cote R, Esrig D, Groshen S, Jones P, SKINNER D . p53 and treatment of bladder cancer. Nature. 1997; 385(6612):123-5. DOI: 10.1038/385123b0. View

Lowe S, Ruley H, Jacks T, Housman D . p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 1993; 74(6):957-67. DOI: 10.1016/0092-8674(93)90719-7. View

Huang H, Huang C, Yen J . Mcl-1 is a common target of stem cell factor and interleukin-5 for apoptosis prevention activity via MEK/MAPK and PI-3K/Akt pathways. Blood. 2000; 96(5):1764-71. View

Zhan Q, Fan S, Bae I, Guillouf C, Liebermann D, OConnor P . Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene. 1994; 9(12):3743-51. View

10.

Erenpreisa J, Cragg M . Mitotic death: a mechanism of survival? A review. Cancer Cell Int. 2002; 1(1):1. PMC: 101225. DOI: 10.1186/1475-2867-1-1. View

11.

Hartmann A, Blaszyk H, McGovern R, Schroeder J, Cunningham J, de Vries E . p53 gene mutations inside and outside of exons 5-8: the patterns differ in breast and other cancers. Oncogene. 1995; 10(4):681-8. View

12.

Lomo J, Blomhoff H, Jacobsen S, Krajewski S, Reed J, Smeland E . Interleukin-13 in combination with CD40 ligand potently inhibits apoptosis in human B lymphocytes: upregulation of Bcl-xL and Mcl-1. Blood. 1997; 89(12):4415-24. View

13.

Zhan Q, Bae I, Kastan M, Fornace Jr A . The p53-dependent gamma-ray response of GADD45. Cancer Res. 1994; 54(10):2755-60. View

14.

Michieli P, Chedid M, Lin D, PIERCE J, Mercer W, Givol D . Induction of WAF1/CIP1 by a p53-independent pathway. Cancer Res. 1994; 54(13):3391-5. View

15.

Sheikh M, ROCHEFORT H, Garcia M . Overexpression of p21WAF1/CIP1 induces growth arrest, giant cell formation and apoptosis in human breast carcinoma cell lines. Oncogene. 1995; 11(9):1899-905. View

16.

Reynolds J, Li J, Craig R, Eastman A . BCL-2 and MCL-1 expression in Chinese hamster ovary cells inhibits intracellular acidification and apoptosis induced by staurosporine. Exp Cell Res. 1996; 225(2):430-6. DOI: 10.1006/excr.1996.0194. View

17.

Finlay C, Hinds P, Tan T, Eliyahu D, Oren M, Levine A . Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988; 8(2):531-9. PMC: 363177. DOI: 10.1128/mcb.8.2.531-539.1988. View

18.

Puthier D, Bataille R, Amiot M . IL-6 up-regulates mcl-1 in human myeloma cells through JAK / STAT rather than ras / MAP kinase pathway. Eur J Immunol. 1999; 29(12):3945-50. DOI: 10.1002/(SICI)1521-4141(199912)29:12<3945::AID-IMMU3945>3.0.CO;2-O. View

19.

Baekelandt M, Holm R, Nesland J, Trope C, Kristensen G . Expression of apoptosis-related proteins is an independent determinant of patient prognosis in advanced ovarian cancer. J Clin Oncol. 2000; 18(22):3775-81. DOI: 10.1200/JCO.2000.18.22.3775. View

20.

Maeta Y, Tsujitani S, Matsumoto S, Yamaguchi K, Tatebe S, Kondo A . Expression of Mcl-1 and p53 proteins predicts the survival of patients with T3 gastric carcinoma. Gastric Cancer. 2004; 7(2):78-84. DOI: 10.1007/s10120-004-0272-9. View