Gene expression profile analysis identifies metastasis and chemoresistance-associated genes in epithelial ovarian carcinoma cells

Abstract

The purpose of this study was to identify genes that associated with higher ability of metastasis and chemotherapic resistance in epithelial ovarian carcinoma (EOC) cells. An oligonucleotide microarray with probe sets complementary to 41,000+ unique human genes and transcripts was used to determine whether gene expression profile may differentiate three epithelial ovarian cell lines (RMG-I-C, COC1 and HO8910) from their sub-lines (RMG-I-H, COCI/DDP and HO8910/PM) with higher ability of metastasis and chemotherapic resistance. Quantitative real-time PCR and immunohistochemical staining validated the microarray results. Hierarchic cluster analysis of gene expression identified 49 genes that exhibited ≥2.0-fold change and P value ≤0.05. Highly differential expression of GCET2, NLRP4, FOXP1 and SNX29 genes was validated by quantitative PCR in all cell line samples. Finally, FOXP1 was validated at the protein level by immunohistochemistry in paraffin embedded ovarian tissues (i.e., for metastasis, 15 primary EOC and 10 omental metastasis [OM]; for chemoresistance, 13 sensitive and 13 resistant EOC). The identification of higher ability of metastasis and chemotherapic resistance-associated genes may provide a foundation for the development of new type-specific diagnostic strategies and treatment for metastasis and chemotherapic resistance in epithelial ovarian cancer.

Functionally Coherent Transcription Factor Target Networks Illuminate Control of Epithelial Remodelling

“…SNX29 is poorly characterised and ectopic expression significantly reduced invasion in a SNAI1-dependent manner ( Figure 6). Since we obtained these results, SNX29 downregulation was associated with metastasis and chemoresistance in ovarian carcinoma (Zhu et al, 2015), consistent with SNX29 inhibition of invasion driven by Snail. ATG3 is an E2-like enzyme required for autophagy and mitochondrial homeostasis (Doherty and Baehrecke, 2018), ATG3 overexpression significantly increased MCF7 invasion.…”

WITHDRAWN: Correlation between FOXP1 and ER/PR expression in endometrial carcinoma

“…According to available reports, however, the positive expression rate of FOXP1 in the cytoplasm varies greatly, from negative to 90% (median: 30%) [14,15]. Our preliminary study demonstrated that the mRNA expression level of FOXP1 was decreased in highly metastatic and drug-resistant ovarian cancer cell lines associated with ovarian cancer metastasis [10]. With increasing malignancy of ovarian tumors, the nucleus expression of FOXP1 became reduced, and FOXP1 and the ER co-localized in the cytoplasm; coimmunoprecipitation experiments showed that FOXP1 bound both ERα and ERβ [5].…”

“…It plays an important role in the regulation of B cell development and monocyte differentiation, and participates in cardiac valve morphodifferentiation and lung development [4]. Numerous studies have shown that the expression level of FOXP1 shows a marked change in tumor tissues, being lower in renal, breast, ovarian, lung and prostate cancers than in normal tissues [5][6][7][8][9][10], but is increased in malignant tumors such as lymphoma, which indicates that FOXP1 may have other roles except as an anti-oncogene [11][12][13].…”

Inflammatory pathway genes associated with inter-individual variability in the trajectories of morning and evening fatigue in patients receiving chemotherapy

“…This change is predicted to be tolerated by SIFT and benign by PolyPhen-2. While no studies were found that described the effect of NLRP4 rs17857373, NLRP4 overexpression was associated with a diagnosis of bladder cancer [119], with an increased potential for metastasis and CTX resistance in women with epithelial ovarian cancer [120], and with periodontal disease [118]. In our study, patients who were homozygous or heterozygous for the rare G allele were predicted to have evening fatigue scores below the clinically meaningful cutoff at all six assessments (Figure 5B).…”