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. 2010 May;117(2):159-69.
doi: 10.1016/j.ygyno.2010.01.041. Epub 2010 Feb 23.

Analysis of chemotherapy response programs in ovarian cancers by the next-generation sequencing technologies

Lihua Cheng  1 , Wei Lu, Bhushan Kulkarni, Tanja Pejovic, Xiaowei Yan, Jung-Hsien Chiang, Leroy Hood, Kunle Odunsi, Biaoyang Lin
Affiliations

Analysis of chemotherapy response programs in ovarian cancers by the next-generation sequencing technologies

Lihua Cheng et al. Gynecol Oncol. 2010 May.

Abstract

Objective: To understand the chemotherapy response program in ovarian cancer cells at deep transcript sequencing levels.

Methods: Two next-generation sequencing technologies--MPSS (massively parallel signature sequencing) and SBS (sequencing by synthesis)--were used to sequence the transcripts of IGROV1 and IGROV1-CP cells, and to sequence the transcripts of a highly chemotherapy responsive and a highly chemotherapy resistant ovarian cancer tissue.

Results: We identified 3422 signatures (2957 genes) that are significantly different between IGROV1 and IGROV1-CP cells (P<0.001). Gene Ontology (GO) term GO:0001837 (epithelial-to-mesenchymal transition) and GO:0034330 (cell junction assembly and maintenance) are enriched in genes that are over expressed in IGROV1-CP cells while apoptosis-related GO terms are enriched in genes over expressed in IGROV1 cells. We identified 1187 tags (corresponding to 1040 genes) that are differentially expressed between the chemotherapy responsive and the persistently chemotherapy resistant ovarian cancer tissues. GO term GO:0050673 (epithelial cell proliferation) and GO:0050678 (regulation of epithelial cell proliferation) are enriched in the genes over expressed in the chemotherapy resistant tissue while the GO:0007229 (integrin-mediated signaling pathway) is enriched in the genes over expressed in the chemotherapy sensitive tissue. An integrative analysis identified 111 common differentially expressed genes including two bone morphogenetic proteins (BMP4 and BMP7), six solute carrier proteins (SLC10A3, SLC16A3, SLC25A1, SLC35B3, SLC7A5 and SLC7A7), transcription factor POU5F1 (POU class 5 homeobox 1), and KLK10 (kallikrein-related peptidase 10). A network analysis revealed a subnetwork with three genes BMP7, NR2F2 and AP2B1 that were consistently over expressed in the chemoresistant tissue or cells compared to the chemosensitive tissue or cells.

Conclusion: Our database offers the first comprehensive view of the digital transcriptomes of ovarian cancer cell lines and tissues with different chemotherapy response phenotypes.

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Conflict of interest statement

Conflict of Interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
A chart showing the over represented Gene Ontology terms in genes over expressed in IGROV1-CP cells comparing to IGROV1 cells. The shade of the red color indicates the P values of enrichments [Log10(P)].
Figure 2
Figure 2
A chart showing the over represented Gene Ontology terms in genes over expressed in IGROV1 cells comparing to IGROV1-CP cells. The shade of the blue-cyan color indicates the P values of enrichments [Log10(P)].
Figure 3
Figure 3
A chart showing the over represented Gene Ontology terms in genes over expressed in chemosensitive (Chemo-S) or chemoresistant (Chemo-R) tissues. The shade of the blue or red colors indicates the P values of enrichments [Log10(P)].
Figure 4
Figure 4
A subnetwork that is over expressed in the chemoresistant cells compared to the chemosensitive cells. The log2 expression ratios of the chemoresistant tissue to the chemosensitive tissue were overlaid onto the network. Red color indicates over expression and white color indicates no significant differentially expression. Circles indicate nodes (proteins) and lines indicate protein-protein interaction taken from the Human Protein Reference Database (HPRD) (http://www.hprd.org/).
See this image and copyright information in PMC

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