Distinct expression and prognostic value of members of the epidermal growth factor receptor family in ovarian cancer

Zhou, Quan; Hou, Chao-Nan; Yang, Hui; He, Ze; Zuo, Mingzhang

doi:10.2147/cmar.s183769

Cited by 7 publications

(6 citation statements)

References 57 publications

(65 reference statements)

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“…Gene alterations such as mutations, amplifications and deep deletions have been reported to influence cancer patients outcomes (31,48). We found 9% alteration of VCAN in gastric cancer and this was associated with better outcome in terms of DFS for patients.…”

Section: Discussionmentioning

confidence: 51%

VCAN – A novel prognostic marker for gastric cancer

Binang

Wang

Tewara³

et al. 2019

Preprint

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Background Versican (VCAN) is a large aggregating extracellular matrix proteoglycan implicated in the pathogenesis of most human cancers but its role in gastric cancer is not yet elucidated. We designed the present study to investigate the expression, prognostic value, relationship between genetic alterations and patient’s outcome, disease associations, as well as genetic and protein interactions of VCAN in gastric cancer. Methods Expression of VCAN in tumor and normal tissues was studied with ONCOMINE, UALCAN, and GEPIA databases and the human protein atlas. UALCAN, GEPIA, OncoLnc and Kaplan-Meier plotter were used to assess the prognostic values of VCAN in gastric cancer. Subgroup analysis of the clinical significance of VCAN in gastric cancer was done using Kaplan-Meier plotter. Genetic alterations of VCAN and their associations with patient’s outcome were studied with cBioPortal. Open targets platform was used to study diseases associated with VCAN, GeneMANIA was used to obtain the neighbor genes interaction network of VCAN, and STRING was used to examine VCAN interaction with other proteins. Results VCAN was upregulated and associated with clinical cancer stages. High VCAN expression predicted unfavorable outcome for all patients; subgroup analysis showed worse outcomes for patients treated with surgery or other adjuvants (other than 5-FU based adjuvant) but better outcome for patients treated with 5-FU based adjuvant, associating VCAN expression with chemosensitivity to 5-FU based adjuvants, but chemoresistance to other adjuvants. Genetic alteration of VCAN correlated with a favorable outcome in terms of disease-free survival for patients. Also, open targets platform showed that VCAN is associated with gastric cancer and is a potential therapeutic target for the disease. Finally, interaction of VCAN with neighbor genes and proteins revealed that VCAN interacts with genes and proteins that drive tumorigenesis and cancer progression. Conclusion The results of this study show that VCAN is an oncogene in gastric cancer whose expression can be applied as a biomarker for prognostic prediction, selection of appropriate chemotherapy drugs/monitoring of treatment response, and is a potential therapeutic target for gastric cancer.

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Section: Discussionmentioning

confidence: 51%

VCAN – A novel prognostic marker for gastric cancer

Binang

Wang

Tewara³

et al. 2019

Preprint

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“…Mutations and gene amplifications are linked to carcinogenesis; mutant genes cause a gain-of-function phenotype, are involved in tumorigenesis and related to patient outcomes (45). Herein, the percentages of alterations in PTPRG-AS1 and BLACAT2 among patients were identified as 1.1 and 0.2%, respectively.…”

Section: Discussionmentioning

confidence: 89%

Expression levels and associations of five long non‑coding RNAs in gastric cancer and their clinical significance

et al. 2020

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Gastric cancer (GC) is a type of cancer that is commonly diagnosed worldwide due to a lack of early diagnostic, prognostic and therapeutic targets for this disease. The aim of the present study was to examine the expression levels of five long non-coding RNAs, namely PTPRG antisense RNA 1 (PTPRG-AS1), forkhead box P4 antisense RNA 1 (FOXP4-AS1), bladder cancer-associated transcript 2 (BLACAT2), ZXF2 and upregulated in colorectal cancer (UCC), to study their associations with patient characteristics and assess their prognostic efficacy, in order to determine the possibility of their application as GC biomarkers. The expression levels of long non-coding RNAs (lncRNAs) were determined by reverse transcription-quantitative PCR analysis of 61 pairs of GC tissues and adjacent healthy gastric mucosa tissues and GC cell lines. The Chi-square test was conducted to assess the associations of lncRNA expression levels with clinical characteristics of patients. The effect of UCC on GC cell proliferation was determined using in vitro functional experiments. The prognostic efficacy of FOXP4-AS1, BLACAT2 and UCC were examined in the Gene Expression Profiling Interactive Analysis database and those of PTPRG-AS1 were examined in the Kaplan Meier Plot database. Gene alteration frequencies of PTPRG-AS1 and BLACAT2 in GC were identified using the cBioPortal for Cancer Genomics. PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC were found to be upregulated in GC cell lines and GC tissues compared with adjacent normal tissues. PTPRG-AS1 and ZXF2 expression levels were associated with the expression status of the cell proliferation marker Ki67. UCC promoted the proliferation of GC cells in vitro and was associated with lymph node metastasis. Increased expression of FOXP4-AS1 indicated a favorable outcome in terms of disease-free survival, whereas high expression of PTPRG-AS1 was associated with poor survival rates for patients in different GC risk groups. BLACAT2 gene mutation was associated with poor disease-free survival outcome for patients with GC. The results suggest that PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC are potential biomarkers for the detection of GC at the molecular level and may be used as potential targets for GC therapy. The individual roles of these lncRNAs may be utilized for prognostic predictions.

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“…Ovarian cancers express easily detectable or overexpressed levels of HERs. The founding member of the family, the EGFR, is widely overexpressed in ovarian cancer [163,164,165]; while HER2 is overexpressed in a subset of ovarian mucinous tumors [166,167]. There are also examples of upregulation of HER2 mRNA, in the absence of HER2 overexpression in ovarian clear cell carcinomas (OCCCs) [168].…”

Section: Ovarian Cancermentioning

confidence: 99%

Epigenetic Dysregulation at the Crossroad of Women’s Cancer

Kumar

Paul

Rameshwar

et al. 2019

Cancers

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An increasingly number of women of all age groups are affected by cancer, despite substantial progress in our understanding of cancer pathobiology, the underlying genomic alterations and signaling cascades, and cellular-environmental interactions. Though our understanding of women’s cancer is far more complete than ever before, there is no comprehensive model to explain the reasons behind the increased incidents of certain reproductive cancer among older as well as younger women. It is generally suspected that environmental and life-style factors affecting hormonal and growth control pathways might help account for the rise of women’s cancers in younger age, as well, via epigenetic mechanisms. Epigenetic regulators play an important role in orchestrating an orderly coordination of cellular signals in gene activity in response to upstream signaling and/or epigenetic modifiers present in a dynamic extracellular milieu. Here we will discuss the broad principles of epigenetic regulation of DNA methylation and demethylation, histone acetylation and deacetylation, and RNA methylation in women’s cancers in the context of gene expression, hormonal action, and the EGFR family of cell surface receptor tyrosine kinases. We anticipate that a better understanding of the epigenetics of women’s cancers may provide new regulatory leads and further fuel the development of new epigenetic biomarkers and therapeutic approaches.

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Distinct expression and prognostic value of members of the epidermal growth factor receptor family in ovarian cancer

Cited by 7 publications

References 57 publications

VCAN – A novel prognostic marker for gastric cancer

VCAN – A novel prognostic marker for gastric cancer

Expression levels and associations of five long non‑coding RNAs in gastric cancer and their clinical significance

Epigenetic Dysregulation at the Crossroad of Women’s Cancer

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