|
|
- 2016
胃癌的分子机制及靶向诊断研究进展
|
Abstract:
摘要：胃癌的发生发展涉及多个分子信号通路和许多细胞因子，其中比较重要的包括PI3K/AKT、MAPK通路，HER、VEGF/VEGFR、MET等生长因子及受体家族，COX-2、NF-κB、STAT、白介素家族等炎症相关因子，他们参与了胃癌细胞凋亡抑制、增殖促进、周期调控以及胃癌侵袭迁移、血管生成等过程。这些因子在胃癌中特异性表达，可以作为肿瘤标记物用于胃癌的靶向治疗，相应药物多已进入临床试验阶段。在上述理论基础上，胃癌靶向诊断也有了新的进展，闪烁扫描法、内镜等手段逐渐趋于成熟，但特异性探针的研究多处于临床前期阶段，仍有待进一步的发展。
ABSTRACT: Multiple cellular factors and molecular signal pathways including PI3K/AKT pathway; MAPK pathway; growth factors and receptors like HER, VEGF/VEGFR and MET; inflammation-related factors like COX-2, NF-κB, STAT and interleukins, are involved in the occurrence and development of gastric cancer, these factors play a key role in apoptosis inhibition, proliferation promotion and cell cycle regulation of gastric cancer cells, as well as invasion, migration and angiogenesis of stomach malignancy. They are also expressed at a higher level in gastric cancer tissue compared with normal gastric mucosa and characterized as biomarkers, whose target therapies mostly have been in clinical trials. Based on these theoretical foundations, the research on molecular diagnosis of gastric cancer has made some progress.Instruments for target detection tend to be mature. However, the research of molecular probes is still in pre-clinical trials, which remains to be further developed
| [1] | SHI J, YAO D, LIU W, et al. Frequent gene amplification predicts poor prognosis in gastric cancer[J]. Int J Mol Sci, 2012, 13(4):4714-4726. |
| [2] | RAMANATHAN RK, MCDONOUGH SL, KENNECKE HF, et al. Phase 2 study of MK-2206, an allosteric inhibitor of AKT, as second-line therapy for advanced gastric and gastroesophageal junction cancer: A SWOG cooperative group trial (S1005)[J]. Cancer, 2015, 121(13):2193-2197. |
| [3] | HUDIS C, SWANTON C, JANJIGIAN YY, et al. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors[J]. Breast Cancer Res, 2013, 15(6):R110. |
| [4] | LIANG B, WANG S, ZHU XG, et al. Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer[J]. World J Gastroenterol, 2005, 11(5):623-628. |
| [5] | SHI J, ZHANG G, YAO D, et al. Prognostic significance of aberrant gene methylation in gastric cancer[J]. Am J Cancer Res, 2012, 2(1):116-129. |
| [6] | XIE KM, HOU XF, LI MQ, et al. NME1 at the human maternal-fetal interface downregulates titin expression and invasiveness of trophoblast cells via MAPK pathway in early pregnancy[J]. Reproduction, 2010, 139(4):799-808. |
| [7] | MURALIDHARAN-CHARI V, CLANCY J, PLOU C, et al. ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles[J]. Curr Biol, 2009, 19(22):1875-1885. |
| [8] | MARTIN-RICHARD M, GALLEGO R, PERICAY C, et al. Multicenter phase II study of oxaliplatin and sorafenib in advanced gastric adenocarcinoma after failure of cisplatin and fluoropyrimidine treatment. A GEMCAD study[J]. Invest New Drugs, 2013, 31(6):1573-1579. |
| [9] | KIM MA, LEE HS, LEE HE, et al. EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number[J]. Histopathology, 2008, 52(6):738-746. |
| [10] | LIETO E, FERRARACCIO F, ORDITURA M, et al. Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients[J]. Ann Surg Oncol, 2008, 15(1):69-79. |
| [11] | DOUILLARD JY, SIENA S, CASSIDY J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study[J]. J Clin Oncol, 2010, 28(31):4697-4705. |
| [12] | IQBAL S, GOLDMAN B, FENOGLIO-PREISER CM, et al. Southwest Oncology Group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer[J]. Ann Oncol, 2011, 22(12):2610-2615. |
| [13] | ROJO F, TABERNERO J, ALBANELL J, et al. Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma[J]. J Clin Oncol, 2006, 24(26):4309-4316. |
| [14] | KARAYIANNAKIS AJ, SYRIGOS KN, POLYCHRONIDIS A, et al. Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables, patient survival, and tumor surgery[J]. Ann Surg, 2002, 236(1):37-42. |
| [15] | DE HAAS S, DELMAR P, BANSAL AT, et al. Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy[J]. Angiogenesis, 2014, 17(4):909-920. |
| [16] | WANG JY, HSIEH JS, CHEN CC, et al. Alterations of APC, c-met, and p53 genes in tumor tissue and serum of patients with gastric cancers[J]. J Surg Res, 2004, 120(2):242-248. |
| [17] | ANCRILE B, LIM KH, COUNTER CM. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis[J]. Genes Dev, 2007, 21(14):1714-1719. |
| [18] | BOLLRATH J, PHESSE TJ, VON BURSTIN VA, et al. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis[J]. Cancer Cell, 2009, 15(2):91-102. |
| [19] | JACKSON CB, JUDD LM, MENHENIOTT TR, et al. Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression[J]. J Pathol, 2007, 213(2):140-151. |
| [20] | KIM DY, CHA ST, AHN DH, et al. STAT3 expression in gastric cancer indicates a poor prognosis[J]. J Gastroenterol Hepatol, 2009, 24(4):646-651. |
| [21] | KANDA N, SENO H, KONDA Y, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells[J]. Oncogene, 2004, 23(28):4921-4929. |
| [22] | ELLEGALA DB, LEONG-POI H, CARPENTER JE, et al. Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3[J]. Circulation, 2003, 108(3):336-341. |
| [23] | CHEN W, ZHENG R, ZENG H, et al. The updated incidences and mortalities of major cancers in China, 2011[J]. Chin J Cancer, 2015, 34(11):502-507. |
| [24] | IKEDA Y, SAKU M, KISHIHARA F, et al. Effective follow-up for recurrence or a second primary cancer in patients with early gastric cancer[J]. Br J Surg, 2005, 92(2):235-239. |
| [25] | HOHENBERGER P, GRETSCHEL S. Gastric cancer[J]. Lancet, 2003, 362(9380):305-315. |
| [26] | OSAKI M, KASE S, ADACHI K, et al. Inhibition of the PI3K-Akt signaling pathway enhances the sensitivity of Fas-mediated apoptosis in human gastric carcinoma cell line, MKN-45[J]. J Cancer Res Clin Oncol, 2004, 130(1):8-14. |
| [27] | XING CG, ZHU BS, LIU HH, et al. LY294002 induces p53-dependent apoptosis of SGC7901 gastric cancer cells[J]. Acta Pharmacol Sin, 2008, 29(4):489-498. |
| [28] | CHOI WY, JIN CY, HAN MH, et al. Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated apoptosis via down-regulation of AKT and activation of caspase-3[J]. Anticancer Res, 2009, 29(11):4457-4465. |
| [29] | LIU J, FU XQ, ZHOU W, et al. LY294002 potentiates the anti-cancer effect of oxaliplatin for gastric cancer via death receptor pathway[J]. World J Gastroenterol, 2011, 17(2):181-190. |
| [30] | KIM KC, KOH YW, CHANG HM, et al. Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays[J]. Ann Surg Oncol, 2011, 18(10):2833-2840. |
| [31] | YONEMURA Y, NINOMIYA I, YAMAGUCHI A, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer[J]. Cancer Res, 1991, 51(3):1034-1038. |
| [32] | AMEMIYA H, KONO K, MORI Y, et al. High frequency of c-Met expression in gastric cancers producing alpha- fetoprotein[J]. Oncology, 2000, 59(2):145-151. |
| [33] | GONG W, WANG L, YAO JC, et al. Expression of activated signal transducer and activator of transcription 3 predicts expression of vascular endothelial growth factor in and angiogenic phenotype of human gastric cancer[J]. Clin Cancer Res, 2005, 11(4):1386-1393. |
| [34] | ALTORKI NK, CHRISTOS P, PORT JL, et al. Preoperative taxane-based chemotherapy and celecoxib for carcinoma of the esophagus and gastroesophageal junction: results of a phase 2 trial[J]. J Thorac Oncol, 2011, 6(6):1121-1127. |
| [35] | SHAH MA, POWER DG, KINDLER HL, et al. A multicenter, phase Ⅱ study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma[J]. Invest New Drugs, 2011, 29(6):1475-1481. |
| [36] | WU WY, XUE XY, CHEN ZJ, et al. Potentially predictive microRNAs of gastric cancer with metastasis to lymph node[J]. World J Gastroenterol, 2011, 17(31):3645-3651. |
| [37] | GUO XB, JING CQ, LI LP, et al. Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene[J]. World J Gastroenterol, 2011, 17(14):1895-1902. |
| [38] | JOSHI BP, WANG TD. Exogenous molecular probes for targeted imaging in cancer: Focus on multi-modal imaging[J]. Cancers (Basel), 2010, 2(2):1251-1287. |
| [39] | BRANDON D, ALAZRAKI A, HALKAR RK, et al. The role of single-photon emission computed tomography and SPECT/computed tomography in oncologic imaging[J]. Semin Oncol, 2011, 38(1):87-108. |
| [40] | GOETZ M. Molecular imaging in GI endoscopy[J]. Gastrointest Endosc, 2012, 76(6):1207-1209. |
| [41] | ATREYA R, NEUMANN H, NEUFERT C, et al. <em>In vivo</em> imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn’s disease[J]. Nat Med, 2014, 20(3):313-318. |
| [42] | PIERCE MC, JAVIER DJ, RICHARDS-KORTUM R. Optical contrast agents and imaging systems for detection and diagnosis of cancer[J]. Int J Cancer, 2008, 123(9):1979-1990. |
| [43] | WANG P, QU Y, LI C, et al. Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CD146 in gastric cancer[J]. Int J Nanomedicine, 2015, 10:749-763. |
| [44] | JUN HY, PARK SH, KIM HS, et al. Long residence time of ultrasound microbubbles targeted to integrin in murine tumor model[J]. Acad Radiol, 2010, 17(1):54-60. |
| [45] | ZHOU M, WANG C, HU S, et al. 18F-FLT PET/CT imaging is not competent for the pretreatment evaluation of metastatic gastric cancer: a comparison with 18F-FDG PET/CT imaging[J]. Nucl Med Commun, 2013, 34(7):694-700. |
| [46] | ZHANG D, JIA H, WANG Y, et al. A CD44 specific peptide developed by phage display for targeting gastric cancer[J]. Biotechnol Lett, 2015, 37(11):2311-2320. |
| [47] | ZHOU J, JOSHI BP, DUAN X, et al. EGFR overexpressed in colonic neoplasia can be detected on wide-field endoscopic imaging[J]. Clin Transl Gastroenterol, 2015, 6: e101. |
| [48] | JEMAL A, BRAY F, CENTER MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90. |
| [49] | YOSHIOKA K. Scaffold proteins in mammalian MAP kinase cascades[J]. J Biochem, 2004, 135(6):657-661. |
| [50] | LEE SH, LEE JW, SOUNG YH, et al. BRAF and KRAS mutations in stomach cancer[J]. Oncogene, 2003, 22(44):6942-6945. |
| [51] | CORONA G, DEIANA M, INCANI A, et al. Hydroxytyrosol inhibits the proliferation of human colon adenocarcinoma cells through inhibition of ERK1/2 and cyclin D1[J]. Mol Nutr Food Res, 2009, 53(7):897-903. |
| [52] | OH DY, LEE SH, HAN SW, et al. Phase I study of OPB-31121, an oral STAT3 inhibitor, in patients with advanced solid tumors[J]. Cancer Res Treat, 2015, 47(4):607-615. |
| [53] | LI X, ZHANG Y, DING J, et al. Survival prediction of gastric cancer by a seven-microRNA signature[J]. Gut, 2010, 59(5):579-585. |
| [54] | MOTOYAMA K, INOUE H, NAKAMURA Y, et al. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family[J]. Clin Cancer Res, 2008, 14(8):2334-2340. |
| [55] | PETROCCA F, VISONE R, ONELLI MR, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer[J]. Cancer Cell, 2008, 13(3):272-286. |
| [56] | KELLOFF GJ, HOFFMAN JM, JOHNSON B, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development[J]. Clin Cancer Res, 2005, 11(8):2785-2808. |
| [57] | ZHANG D, JIA H, LI W, et al. Screening and identification of a phage display derived peptide that specifically binds to the CD44 protein region encoded by variable exons[J]. J Biomol Screen, 2016, 21(1):44-53. |
| [58] | JOSHI BP, DUAN X, KWON RS, et al. Multimodal endoscope can quantify wide-field fluorescence detection of Barrett’s neoplasia[J]. Endoscopy, 2016, 48(2):A1-A13. |
| [59] | OSAKI M, OSHIMURA M, ITO H. PI3K-Akt pathway: its functions and alterations in human cancer[J]. Apoptosis, 2004, 9(6):667-676. |
| [60] | SONG G, OUYANG G, BAO S. The activation of Akt/PKB signaling pathway and cell survival[J]. J Cell Mol Med, 2005, 9(1):59-71. |
| [61] | PARK CM, PARK MJ, KWAK HJ, et al. Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signaling pathways[J]. Cancer Res, 2006, 66(17):8511-8519. |
| [62] | VIVANCO I, SAWYERS CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer[J]. Nat Rev Cancer, 2002, 2(7):489-501. |
| [63] | BADER AG, KANG S, VOGT PK. Cancer-specific mutations in PIK3CA are oncogenic ？？in vivo？？[J]. Proc Natl Acad Sci USA, 2006, 103(5):1475-1479. |
| [64] | ALMHANNA K, CUBITT CL, ZHANG S, et al. MK-2206, an Akt inhibitor, enhances carboplatinum/paclitaxel efficacy in gastric cancer cell lines[J]. Cancer Biol Ther, 2013, 14(10):932-936. |
| [65] | KOBAYASHI I, SEMBA S, MATSUDA Y, et al. Significance of Akt phosphorylation on tumor growth and vascular endothelial growth factor expression in human gastric carcinoma[J]. Pathobiology, 2006, 73(1):8-17. |
| [66] | DAMMANN R, SCHAGDARSURENGIN U, SEIDEL C, et al. The tumor suppressor RASSF1A in human carcinogenesis: an update[J]. Histol Histopathol, 2005, 20(2):645-663. |
| [67] | ALEJANDRO EU, JOHNSON JD. Inhibition of Raf-1 alters multiple downstream pathways to induce pancreatic beta-cell apoptosis[J]. J Biol Chem, 2008, 283(4):2407-2417. |
| [68] | TAI KY, SHIEH YS, LEE CS, et al. Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-kappaB and Brg-1[J]. Oncogene, 2008, 27(29):4044-4055. |
| [69] | NICHOLSON RI, GEE JM, HARPER ME. EGFR and cancer prognosis[J]. Eur J Cancer, 2001, 37(Suppl 4):S9-15. |
| [70] | ABAD A. New drugs in the treatment of gastric tumors[J]. Clin Transl Oncol, 2008, 10(5):256-261. |
| [71] | HAN SW, OH DY, IM SA, et al. Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer[J]. Br J Cancer, 2009, 100(2):298-304. |
| [72] | SATOH T, LEE KH, RHA SY, et al. Randomized phase II trial of nimotuzumab plus irinotecan versus irinotecan alone as second-line therapy for patients with advanced gastric cancer[J]. Gastric Cancer, 2015, 18(4):824-832. |
| [73] | RAO S, STARLING N, CUNNINGHAM D, et al. Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer[J]. Br J Cancer, 2008, 99(6):868-874. |
| [74] | ROZEN P, SHABTAI EI, LIPHSHITZ I, et al. Risk for colorectal cancer in elderly persons and possible methodologies for their screening[J]. Eur J Gastroenterol Hepatol, 2011, 23(5):431-437. |
| [75] | MATSUI Y, INOMATA M, TOJIGAMORI M, et al. Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model[J]. Int J Oncol, 2005, 27(3):681-685. |
| [76] | JORGENSEN JT. Targeted HER2 treatment in advanced gastric cancer[J]. Oncology, 2010, 78(1):26-33. |
| [77] | KAKEJI Y, KOGA T, SUMIYOSHI Y, et al. Clinical significance of vascular endothelial growth factor expression in gastric cancer[J]. J Exp Clin Cancer Res, 2002, 21(1):125-129. |
| [78] | OHTA M, KONNO H, TANAKA T, et al. The significance of circulating vascular endothelial growth factor (VEGF) protein in gastric cancer[J]. Cancer Lett, 2003, 192(2):215-225. |
| [79] | TAKAHASHI Y, CLEARY KR, MAI M, et al. Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer[J]. Clin Cancer Res, 1996, 2(10):1679-1684. |
| [80] | KUNIYASU H, YASUI W, KITADAI Y, et al. Frequent amplification of the c-met gene in scirrhous type stomach cancer[J]. Biochem Biophys Res Commun, 1992, 189(1):227-232. |
| [81] | TSENG CW, LIN CC, CHEN CN, et al. Integrative network analysis reveals active microRNAs and their functions in gastric cancer[J]. BMC Syst Biol, 2011, 5:99. |
| [82] | ZHU M, ZHANG N, HE S, et al. MicroRNA-106a targets TIMP2 to regulate invasion and metastasis of gastric cancer[J]. FEBS Lett, 2014, 588(4):600-607. |
| [83] | LI Z, ZHAN W, WANG Z, et al. Inhibition of PRL-3 gene expression in gastric cancer cell line SGC7901 via microRNA suppressed reduces peritoneal metastasis[J]. Biochem Biophys Res Commun, 2006, 348(1):229-237. |
| [84] | CORREA P. A human model of gastric carcinogenesis[J]. Cancer Res, 1988, 48(13):3554-3560. |
| [85] | WEBER J, HABERKORN U, MIER W. Cancer stratification by molecular imaging[J]. Int J Mol Sci, 2015, 16(3):4918-4946. |
| [86] | YANG DJ, KIM EE, INOUE T. Targeted molecular imaging in oncology[J]. Ann Nucl Med, 2006, 20(1):1-11. |
| [87] | SMYTH E, SCHODER H, STRONG VE, et al. A prospective evaluation of the utility of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer[J]. Cancer, 2012, 118(22):5481-5488. |
| [88] | YENTZ S, WANG TD. Molecular imaging for guiding oncologic prognosis and therapy in esophageal adenocarcinoma[J]. Hosp Pract (1995), 2011, 39(2):97-106. |
| [89] | MILLER SJ, JOSHI BP, FENG Y, et al. <em>In vivo</em> fluorescence-based endoscopic detection of colon dysplasia in the mouse using a novel peptide probe[J]. PLoS One, 2011, 6(3): e17384. |
| [90] | AIME S, CABELLA C, COLOMBATTO S, et al. Insights into the use of paramagnetic Gd(Ⅲ) complexes in MR-molecular imaging investigations[J]. J Magn Reson Imaging, 2002, 16(4):394-406. |
