Biomedical Center, School of Electronics Engineering, Beijing University of Posts and Telecommunications, Beijing, China.
Cell Biochem Biophys. 2010 Apr;56(2-3):59-71. doi: 10.1007/s12013-009-9071-6.
The aim of this study is to set up single molecular secreted phosphoprotein 1 (SPP1) upstream invasive network of lung adenocarcinoma. This paper proposed an integrated method based on linear programming and a decomposition procedure with integrated analysis of the significant function cluster using Kappa statistics and fuzzy heuristic clustering. Our study proved that only modules appearing in lung adenocarcinoma include cytokine module (CXCL13, GREM1_2 inhibition), cell adhesion module (COL11A1_2 activation; CDH3 inhibition), and receptor binding module (NMU activation; CXCL13, GREM1_2 inhibition), which increase the invasion of cancer cell. We compared skeletal development, signal, biological regulation, sequence variant modules between human normal adjacent tissues and lung adenocarcinoma. SPP1 skeletal development module appears in human normal adjacent tissues (COL11A1_1 activation; COL10A1 inhibition), whereas in lung adenocarcinoma (COL11A1_2, COL1A2 activation); signal module appears in human normal adjacent tissues (COL11A1_1, CXCL13, MMP11, SPINK1 activation; COL10A1, COL3A1 inhibition), whereas in lung adenocarcinoma (COL11A1_2, COL1A2, MMP12 activation; CDH3, CXCL13, GREM1_2, MMP11, SPINK1 inhibition); biological regulation module appears in human normal adjacent tissues (CXCL13, MKI67, PYCR1 activation; NEK2, SPDEF, TOP2A_2, TOX3_1 inhibition), whereas in lung adenocarcinoma (HMGB3, MKI67, NMU, PYCR1, TOX3_2 activation; CXCL13, SPDEF, TOP2A_2 inhibition); sequence variant module appears in human normal adjacent tissues (COL11A1_1, MKI67, MMP11 activation; ASPM, COL10A1, COL3A1, NEK2, TMPRSS4, TOP2A_2 inhibition), whereas in lung adenocarcinoma (COL11A1_2, COL1A2, HMMR, MKI67, MMP12 activation; ABCC3, ASPM, CDH3, MMP11, TOP2A_2 inhibition). It can be deduced that modules above in human normal adjacent tissues reflect the invasive inhibition of normal cells, whereas in lung adenocarcinoma increase the invasion of cancer cell. Our study of SPP1 upstream invasive network may be useful to identify novel and potentially targets for prognosis and therapy of lung adenocarcinoma.
本研究旨在建立肺腺癌中单个分子分泌磷蛋白 1（SPP1）的上游侵袭网络。本文提出了一种基于线性规划的综合方法和一种分解过程，通过使用 Kappa 统计和模糊启发式聚类对显著功能簇进行综合分析。我们的研究证明，只有出现在肺腺癌中的模块包括细胞因子模块（CXCL13、GREM1_2 抑制）、细胞黏附模块（COL11A1_2 激活；CDH3 抑制）和受体结合模块（NMU 激活；CXCL13、GREM1_2 抑制），这会增加癌细胞的侵袭性。我们比较了人类正常相邻组织和肺腺癌之间的骨骼发育、信号、生物调节、序列变异模块。SPP1 骨骼发育模块出现在人类正常相邻组织中（COL11A1_1 激活；COL10A1 抑制），而在肺腺癌中（COL11A1_2、COL1A2 激活）；信号模块出现在人类正常相邻组织中（COL11A1_1、CXCL13、MMP11、SPINK1 激活；COL10A1、COL3A1 抑制），而在肺腺癌中（COL11A1_2、COL1A2、MMP12 激活；CDH3、CXCL13、GREM1_2、MMP11、SPINK1 抑制）；生物调节模块出现在人类正常相邻组织中（CXCL13、MKI67、PYCR1 激活；NEK2、SPDEF、TOP2A_2、TOX3_1 抑制），而在肺腺癌中（HMGB3、MKI67、NMU、PYCR1、TOX3_2 激活；CXCL13、SPDEF、TOP2A_2 抑制）；序列变异模块出现在人类正常相邻组织中（COL11A1_1、MKI67、MMP11 激活；ASPM、COL10A1、COL3A1、NEK2、TMPRSS4、TOP2A_2 抑制），而在肺腺癌中（COL11A1_2、COL1A2、HMMR、MKI67、MMP12 激活；ABCC3、ASPM、CDH3、MMP11、TOP2A_2 抑制）。可以推断，人类正常相邻组织中的上述模块反映了正常细胞的侵袭抑制，而在肺腺癌中则增加了癌细胞的侵袭性。我们对 SPP1 上游侵袭网络的研究可能有助于确定肺腺癌预后和治疗的新的潜在靶点。
