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Conference Paper: Genomics approach to identify growth factor and drug transporter associated with liver cancer recurrence and chemo-resistance
Title | Genomics approach to identify growth factor and drug transporter associated with liver cancer recurrence and chemo-resistance |
---|---|
Authors | |
Issue Date | 2012 |
Publisher | Springer New York LLC. The Journal's web site is located at http://www.springer.com/west/home/medicine?SGWID=4-10054-70-173733513-0 |
Citation | The 22nd Congress of the Asian Pacific Association for the Study of the Liver (APASL 2012), Taipei, Taiwan, 16-19 February 2012. In Hepatology International, 2012, v. 6 n. 1, p. 26, abstract no. PS05-01 How to Cite? |
Abstract | Background: Liver cancer is the third leading cause of cancer death
globally. Surgery is the mainstay for early stage patients but recurrence
is still common. Chemotherapy has been widely used to treat
advanced liver cancer but with marginal efficacy. Recent evidences
have shown the role of tumor initiating cells on chemo-resistance and
recurrence, however, the key genes remind inconclusive. Recently,
we have demonstrated that the novel growth factor granulin-epithelin
precursor (GEP) and drug transporter ABCB5 were associated with
chemo-resistance and recurrence-free survival (Gastroenterology
2011). GEP has been identified as a potential therapeutic target for
liver cancer in our earlier genomic studies. The aim of the study is to
identify additional drug transporters with clinical relevance.
Methods: The liver cancer gene expression profiles reported previously
were re-examined for all the ATP-binding transporters. The
gene of interest were further validated in an independent cohort using
real-time quantitative RT-PCR.
Results: ABCF1 was upregulated in tumor compared with non-tumor
(P/0.001), and increased ABCF1 was associated with poor recurrence-
free survival (log-rank test, P = 0.001). Functionally,
suppression of ABCF1 rendered the liver cancer cells sensitive to
chemotherapeutic agents. Liver cancer cells that were positive for
GEP and ABCB5/ABCF1 showed enhanced expression of the stem
cell related signaling molecules-catenin, Oct4 and Nanog.
Conclusions: In summary, chemo-resistance and cancer recurrence
are dictated by a subset of cells expressing GEP and ABC transporters.
Targeting the novel growth factor GEP and drug transporters,
in combination with chemotherapy, could provide novel treatment
modalities to eradicate the aggressive hepatic tumor initiating cells. |
Description | Oral Presentation |
Persistent Identifier | http://hdl.handle.net/10722/165656 |
ISSN | 2023 Impact Factor: 5.9 2023 SCImago Journal Rankings: 1.813 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Cheung, ST | en_US |
dc.contributor.author | Cheung, PFY | en_US |
dc.contributor.author | Cheng, CKC | en_US |
dc.contributor.author | Fan, ST | en_US |
dc.date.accessioned | 2012-09-20T08:21:41Z | - |
dc.date.available | 2012-09-20T08:21:41Z | - |
dc.date.issued | 2012 | en_US |
dc.identifier.citation | The 22nd Congress of the Asian Pacific Association for the Study of the Liver (APASL 2012), Taipei, Taiwan, 16-19 February 2012. In Hepatology International, 2012, v. 6 n. 1, p. 26, abstract no. PS05-01 | en_US |
dc.identifier.issn | 1936-0533 | - |
dc.identifier.uri | http://hdl.handle.net/10722/165656 | - |
dc.description | Oral Presentation | - |
dc.description.abstract | Background: Liver cancer is the third leading cause of cancer death globally. Surgery is the mainstay for early stage patients but recurrence is still common. Chemotherapy has been widely used to treat advanced liver cancer but with marginal efficacy. Recent evidences have shown the role of tumor initiating cells on chemo-resistance and recurrence, however, the key genes remind inconclusive. Recently, we have demonstrated that the novel growth factor granulin-epithelin precursor (GEP) and drug transporter ABCB5 were associated with chemo-resistance and recurrence-free survival (Gastroenterology 2011). GEP has been identified as a potential therapeutic target for liver cancer in our earlier genomic studies. The aim of the study is to identify additional drug transporters with clinical relevance. Methods: The liver cancer gene expression profiles reported previously were re-examined for all the ATP-binding transporters. The gene of interest were further validated in an independent cohort using real-time quantitative RT-PCR. Results: ABCF1 was upregulated in tumor compared with non-tumor (P/0.001), and increased ABCF1 was associated with poor recurrence- free survival (log-rank test, P = 0.001). Functionally, suppression of ABCF1 rendered the liver cancer cells sensitive to chemotherapeutic agents. Liver cancer cells that were positive for GEP and ABCB5/ABCF1 showed enhanced expression of the stem cell related signaling molecules-catenin, Oct4 and Nanog. Conclusions: In summary, chemo-resistance and cancer recurrence are dictated by a subset of cells expressing GEP and ABC transporters. Targeting the novel growth factor GEP and drug transporters, in combination with chemotherapy, could provide novel treatment modalities to eradicate the aggressive hepatic tumor initiating cells. | - |
dc.language | eng | en_US |
dc.publisher | Springer New York LLC. The Journal's web site is located at http://www.springer.com/west/home/medicine?SGWID=4-10054-70-173733513-0 | - |
dc.relation.ispartof | Hepatology International | en_US |
dc.rights | The original publication is available at www.springerlink.com | - |
dc.title | Genomics approach to identify growth factor and drug transporter associated with liver cancer recurrence and chemo-resistance | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.email | Cheung, ST: stcheung@hkucc.hku.hk | en_US |
dc.identifier.email | Cheung, PFY: cphyllis@hkucc.hku.hk | en_US |
dc.identifier.email | Cheng, CKC: ckccheng@hkucc.hku.hk | en_US |
dc.identifier.email | Fan, ST: stfan@hku.hk | en_US |
dc.identifier.authority | Cheung, ST=rp00457 | en_US |
dc.identifier.authority | Fan, ST=rp00355 | en_US |
dc.identifier.doi | 10.1007/s12072-011-9330-7 | - |
dc.identifier.hkuros | 211412 | en_US |
dc.identifier.hkuros | 211293 | - |
dc.identifier.volume | 6 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 26, abstract no. PS05-01 | - |
dc.identifier.epage | 26, abstract no. PS05-01 | - |
dc.identifier.isi | WOS:000300362800001 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 1936-0533 | - |