Human kallikrein-related peptidase 6 (KLK6) and 13 (KLK13) are involved in ovarian carcinoma pathogenesis
Thesis (Ph.D.)--Memorial University of Newfoundland, 2010. Medicine Includes bibliographical references It is estimated in 2009 that 2500 Canadian women were diagnosed and 1750 women lost their lives to epithelial ovarian cancer. This malignancy has a high mortality rate because the majority of wome...
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Format: | Thesis |
Language: | English |
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2010
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Online Access: | http://collections.mun.ca/cdm/ref/collection/theses4/id/50832 |
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ftmemorialunivdc:oai:collections.mun.ca:theses4/50832 |
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institution |
Open Polar |
collection |
Memorial University of Newfoundland: Digital Archives Initiative (DAI) |
op_collection_id |
ftmemorialunivdc |
language |
English |
topic |
Kallikrein Ovaries--Cancer--Diagnosis Ovaries--Cancer--Genetic aspects Kallikreins Ovarian Neoplasms--diagnosis Ovarian Neoplasms--etiology |
spellingShingle |
Kallikrein Ovaries--Cancer--Diagnosis Ovaries--Cancer--Genetic aspects Kallikreins Ovarian Neoplasms--diagnosis Ovarian Neoplasms--etiology White, Nicole, 1978- Human kallikrein-related peptidase 6 (KLK6) and 13 (KLK13) are involved in ovarian carcinoma pathogenesis |
topic_facet |
Kallikrein Ovaries--Cancer--Diagnosis Ovaries--Cancer--Genetic aspects Kallikreins Ovarian Neoplasms--diagnosis Ovarian Neoplasms--etiology |
description |
Thesis (Ph.D.)--Memorial University of Newfoundland, 2010. Medicine Includes bibliographical references It is estimated in 2009 that 2500 Canadian women were diagnosed and 1750 women lost their lives to epithelial ovarian cancer. This malignancy has a high mortality rate because the majority of women are diagnosed in late stage disease where the 5 year survival rate is only 20%. Late diagnosis is a result of the lack of an effective screening marker. Currently, CA125 is the only marker that is used for ovarian cancer patients and it is used primarily to monitor disease recurrence after treatment. Unfortunately, CA125 lacks the sensitivity and specificity to be used for early detection of ovarian cancer. Recently, a new group of genes, the human kallikrein-related peptidase (KLK) family, has been implicated in ovarian cancer and are being investigated as potential new biomarkers for the malignancy. In particular, KLK 13 has been shown to have increased expression in ovarian cancer. KLK13 has increased expression in the ovarian cancer cell lines CAOV-3, OVCAR-3, and SKOV-3 when compared to the IOSE cell line and is involved in cell motility. Increased KLK13 expression increases migration in the epithelial cell lines IOSE and Mv1Lu. Also, when KLK13 expression was decreased in the ovarian cancer cell line SKOV-3, which has high endogenous KLK13 expression levels, there was a decrease in cellular migration. Increased KLK13 expression in IOSE cells increased cellular invasion through the basement membrane. These data together suggest KLK 13 plays a role in ovarian carcinogenesis and may be a potential therapeutic target. In order to see if KLK expression had any prognostic significance in ovarian cancer patients, paraffin embedded ovarian cancer samples were analyzed for KLK6 and KLK13 mRNA expression. High expression levels of both KLK6 and KLK13 were associated with invasive ovarian cancer. Also, high KLK6 expression was associated with late stage ovarian cancer and serous histological type. Both KLK6 and KLK13 were also shown to be markers of poor prognosis as patients with high kallikrein expression were more likely to have a recurrence than patients with low KLK expression. When KLK6, KLK13 and Mucl6 were assessed for the ability to detect ovarian cancer, the genes detected 56%, 50%, and 56%, respectively, early stage (Stage I and II) ovarian cancer patients. When all three markers were used in combination, the sensitivity of the test improved to 84%. There was no significant change in the specificity or positive predictive value, but the negative predictive value increased from 33% using the individual markers to 58% when all three markers were combined. These data together suggest KLK6 and KLK 13 are involved in ovarian cancer tumorigenesis. Both KLK6 and KLK13 are potential new markers and possible therapeutic targets for ovarian carcinoma. |
author2 |
Memorial University of Newfoundland. Faculty of Medicine |
format |
Thesis |
author |
White, Nicole, 1978- |
author_facet |
White, Nicole, 1978- |
author_sort |
White, Nicole, 1978- |
title |
Human kallikrein-related peptidase 6 (KLK6) and 13 (KLK13) are involved in ovarian carcinoma pathogenesis |
title_short |
Human kallikrein-related peptidase 6 (KLK6) and 13 (KLK13) are involved in ovarian carcinoma pathogenesis |
title_full |
Human kallikrein-related peptidase 6 (KLK6) and 13 (KLK13) are involved in ovarian carcinoma pathogenesis |
title_fullStr |
Human kallikrein-related peptidase 6 (KLK6) and 13 (KLK13) are involved in ovarian carcinoma pathogenesis |
title_full_unstemmed |
Human kallikrein-related peptidase 6 (KLK6) and 13 (KLK13) are involved in ovarian carcinoma pathogenesis |
title_sort |
human kallikrein-related peptidase 6 (klk6) and 13 (klk13) are involved in ovarian carcinoma pathogenesis |
publishDate |
2010 |
url |
http://collections.mun.ca/cdm/ref/collection/theses4/id/50832 |
genre |
Newfoundland studies University of Newfoundland |
genre_facet |
Newfoundland studies University of Newfoundland |
op_source |
Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries |
op_relation |
Electronic Theses and Dissertations (25.81 MB) -- http://collections.mun.ca/PDFs/theses/White_Nicole.pdf a3497942 http://collections.mun.ca/cdm/ref/collection/theses4/id/50832 |
op_rights |
The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. |
_version_ |
1766113244356804608 |
spelling |
ftmemorialunivdc:oai:collections.mun.ca:theses4/50832 2023-05-15T17:23:33+02:00 Human kallikrein-related peptidase 6 (KLK6) and 13 (KLK13) are involved in ovarian carcinoma pathogenesis White, Nicole, 1978- Memorial University of Newfoundland. Faculty of Medicine 2010 xvii, 5-212 leaves : ill. (some col.) Image/jpeg; Application/pdf http://collections.mun.ca/cdm/ref/collection/theses4/id/50832 Eng eng Electronic Theses and Dissertations (25.81 MB) -- http://collections.mun.ca/PDFs/theses/White_Nicole.pdf a3497942 http://collections.mun.ca/cdm/ref/collection/theses4/id/50832 The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries Kallikrein Ovaries--Cancer--Diagnosis Ovaries--Cancer--Genetic aspects Kallikreins Ovarian Neoplasms--diagnosis Ovarian Neoplasms--etiology Text Electronic thesis or dissertation 2010 ftmemorialunivdc 2015-08-06T19:21:57Z Thesis (Ph.D.)--Memorial University of Newfoundland, 2010. Medicine Includes bibliographical references It is estimated in 2009 that 2500 Canadian women were diagnosed and 1750 women lost their lives to epithelial ovarian cancer. This malignancy has a high mortality rate because the majority of women are diagnosed in late stage disease where the 5 year survival rate is only 20%. Late diagnosis is a result of the lack of an effective screening marker. Currently, CA125 is the only marker that is used for ovarian cancer patients and it is used primarily to monitor disease recurrence after treatment. Unfortunately, CA125 lacks the sensitivity and specificity to be used for early detection of ovarian cancer. Recently, a new group of genes, the human kallikrein-related peptidase (KLK) family, has been implicated in ovarian cancer and are being investigated as potential new biomarkers for the malignancy. In particular, KLK 13 has been shown to have increased expression in ovarian cancer. KLK13 has increased expression in the ovarian cancer cell lines CAOV-3, OVCAR-3, and SKOV-3 when compared to the IOSE cell line and is involved in cell motility. Increased KLK13 expression increases migration in the epithelial cell lines IOSE and Mv1Lu. Also, when KLK13 expression was decreased in the ovarian cancer cell line SKOV-3, which has high endogenous KLK13 expression levels, there was a decrease in cellular migration. Increased KLK13 expression in IOSE cells increased cellular invasion through the basement membrane. These data together suggest KLK 13 plays a role in ovarian carcinogenesis and may be a potential therapeutic target. In order to see if KLK expression had any prognostic significance in ovarian cancer patients, paraffin embedded ovarian cancer samples were analyzed for KLK6 and KLK13 mRNA expression. High expression levels of both KLK6 and KLK13 were associated with invasive ovarian cancer. Also, high KLK6 expression was associated with late stage ovarian cancer and serous histological type. Both KLK6 and KLK13 were also shown to be markers of poor prognosis as patients with high kallikrein expression were more likely to have a recurrence than patients with low KLK expression. When KLK6, KLK13 and Mucl6 were assessed for the ability to detect ovarian cancer, the genes detected 56%, 50%, and 56%, respectively, early stage (Stage I and II) ovarian cancer patients. When all three markers were used in combination, the sensitivity of the test improved to 84%. There was no significant change in the specificity or positive predictive value, but the negative predictive value increased from 33% using the individual markers to 58% when all three markers were combined. These data together suggest KLK6 and KLK 13 are involved in ovarian cancer tumorigenesis. Both KLK6 and KLK13 are potential new markers and possible therapeutic targets for ovarian carcinoma. Thesis Newfoundland studies University of Newfoundland Memorial University of Newfoundland: Digital Archives Initiative (DAI) |