Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy

Li, Jian; Li, Zhennan; Yu, Long-Chuan; Bao, Qian-Lei; Wu, Jianrong; Shi, Shun‐Bing; Li, Xiaoqin

doi:10.1016/j.lungcan.2009.09.013

Cited by 60 publications

(29 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, overexpression of MRP1 has been related to poor prognosis in patients with localized non-small cell lung carcinoma receiving cisplatin-based chemotherapy, a substrate of MRP1 (23)(24)(25). Similarly, the expression of MRP1 was associated with an increased risk of failure in cases with small tumors, in node-negative tumors and in node-positive patients in a retrospective series of patients with localized breast cancer, who received adjuvant systemic chemotherapy based on MRP1 substrates such as cyclophosphamide and methotrexate (26).…”

Section: Discussionmentioning

confidence: 99%

MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study

Martin‐Broto

Gutiérrez

Ramos

et al. 2014

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Patients with localized high-risk soft tissue sarcomas (STS) of the limbs and trunk wall still have a considerable metastatic recurrence rate of more than 50%, in spite of adjuvant chemotherapy. This drugceiling effect of chemotherapy in sarcoma setting could be explained, at least partially, by multidrug resistance (MDR) mechanisms. The aim of this study was to ascertain whether mRNA and protein expression of ABCB1 (P-glycoprotein), ABCC1 (MRP1), and GSTA1 (glutathione S-transferase pi) was prognostic in localized high-risk STS. Immunohistochemistry and reverse transcriptase-PCR studies were performed from biopsies at the time of diagnosis. Patients of this series were prospectively enrolled into a phase III trial that compared three versus five cycles of epirubicin plus ifosfamide. The series of 102 patients found 41 events of recurrence and 37 of death with a median follow-up of 68 months. In univariate analysis, variables with a statistically significant relationship with relapse-free survival (RFS) were: MRP1 expression (5-year RFS rate of 23% in positive cases and 63% in negative cases, P ¼ 0.029), histology (5-year RFS rate of 74% in undifferentiated pleomorphic sarcoma and 43% in synovial sarcoma, P ¼ 0.028), and ABCC1 expression (5-year RFS rate of 33% in overexpression and 65% in downregulation, P ¼ 0.012). Combined ABCC1/MRP1 was the only independent prognostic factor for both RFS (HR ¼ 2.704, P ¼ 0.005) and overall survival (HR ¼ 2.208, P ¼ 0.029). ABCC1/MRP1 expression shows robust prognostic relevance in patients with localized high-risk STS treated with anthracycline-based chemotherapy, which is the standard front line treatment in STS. This finding deserves attention as it points to a new targetable protein in STS.

show abstract

Section: Discussionmentioning

confidence: 99%

MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study

Martin‐Broto

Gutiérrez

Ramos

et al. 2014

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…MVP is present in normal tissues, including bronchus, digestive tract and macrophages, and in malignant cells, including acute myeloid leukemia, ovarian cancer and colon carcinoma (29). The high degree of conservation and ubiquitous expression of MVP suggest that this protein exerts crucial cellular functions (29 evidence from previous studies has demonstrated that high messenger (m)RNA and protein levels of MVP are associated with resistance to antineoplastic agents and reduced survival in certain types of cancer, including ovarian cancer (22,(30)(31)(32). Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation among the human population, and are often associated with inter-individual diversity in various malignancies regarding the patient's susceptibility to disease, drug response, toxicity and survival (33)(34)(35)(36).…”

Section: Introductionmentioning

confidence: 99%

Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer

Wang

2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. The human major vault protein (MVP) has been linked to the development of multidrug resistance in cancer cells, and overexpression of MVP has been observed in ovarian cancer tissues. The aim of the present study was to investigate the association between single nucleotide polymorphisms (SNPs) in the MVP gene and the tumor response to platinum-based chemotherapy and survival of patients affected by epithelial ovarian cancer (EOC), in addition to confirm whether tetra-primer amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) is an accurate genotyping method. For this purpose, two polymorphisms in the MVP gene, namely reference SNP (rs)1057451 and rs4788186, were selected from the data obtained by the International haplotype map (HapMap) Project regarding Chinese Han population, and were evaluated by tetra-primer ARMS-PCR. Upon validation by DNA sequencing, the association of these polymorphisms with platinum resistance, progression-free survival (PFS) and overall survival (OS) in patients with EOC was assessed. The results of tetra-primer ARMS-PCR were in agreement with those derived from DNA sequencing. No significant differences were observed between platinum-sensitive and platinum-resistant cohorts in terms of allele and genotype distribution of these two polymorphisms in the MVP gene, which were not associated with PFS or OS. However, a trend toward prolonged PFS was observed in patients carrying the heterozygous AG allele at the rs4788186 locus. These results suggest that rs1057451 and rs4788186 variants in the MVP gene are not associated with favorable therapeutic response to platinum or longer survival in Chinese Han patients affected by EOC. In addition, the data of the present study confirm that tetra-primer ARMS-PCR is a trustworthy and economical genotyping method.

show abstract

“…ERCC1 is a DNA repair endonuclease responsible for the 5'-incision during DNA excision repair. Overexpression of ERCC1 is correlated to resistance to platinum-based chemotherapy (10 shown that high TUBB3 expression is associated with resistance to docetaxel and paclitaxel (11,12). TYMS is the enzyme used for DNA synthesis and repair.…”

Section: Introductionmentioning

confidence: 99%

“…However, drug resistance causes unsatisfactory clinical responses to these medicines. Therefore, it is essential to understand the molecular markers associated with resistance to these medicines, to aid oncologists in choosing the more effective anti-tumor drugs for patients to achieve the most advantageous potential outcomes.The major molecular markers associated with clinical response to gefitinib or chemotherapy in NSCLC include the status of EGFR, K-RAS mutations and mRNA expression levels of excision repair cross-complementing 1 (ERCC1), class III β-tubulin (TUBB3), thymidylate synthase (TYMS), ribonucleotide reductase subunit M1 (RRM1) and EGFR (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). EGFR is a member of the ErbB family of receptors.…”

mentioning

confidence: 99%

EGFR and K-RAS mutations and ERCC1, TUBB3, TYMS, RRM1 and EGFR mRNA expression in non-small cell lung cancer: Correlation with clinical response to gefitinib or chemotherapy

Guo

Zhang

et al. 2015

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Personalizing medicines has refined the traditional treatments for non-small-cell lung cancer (NSCLC). In the present study, efforts towards personalizing delivery of care based on the status of EGFR and K-RAS mutations, and mRNA expression levels of ERCC1, TUBB3, TYMS, RRM1 and EGFR by choosing appropriate treatments for 52 patients with NSCLC were discussed. Among these 52 NSCLC patients, there were 14 patients treated with gefitinib. Ten patients with EGFR exon 21 point mutations or exon 19 deletions had better treatment outcomes following gefitinib treatment (71.4%). There were 38 patients treated with platinum-based chemotherapy. Docetaxel-platinum based chemotherapy was chosen as the first-line treatment when the patients had low or median ERCC1/TUBB3 expression and gemcitabine-platinum based chemotherapy was chosen when the patients had low or median ERCC1/RRM1 expression. In total, 26 cases had mRNA expression levels of ERCC1/TUBB3 or ERCC1/RRM1 that could be used to predict the treatment outcomes of chemotherapy (68.4%). The present results indicated that the mutation status of EGFR, as well as the mRNA expression levels of ERCC1, TUBB3 and RRM1, could be used as predictors of the response to gefitinib or chemotherapy. IntroductionLung cancer, of which nearly 80-85% is diagnosed as non-small-cell lung cancer (NSCLC), is one of the leading causes of fatality worldwide (1). The adjuvant chemotherapy, including the combinations of platinum and cytotoxic agents (such as docetaxel and gemcitabine) and epidermal growth factor receptor (EGFR)-targeted therapy, such as gefitinib (AstraZeneca, London, UK), has become common treatments for NSCLC (2). However, drug resistance causes unsatisfactory clinical responses to these medicines. Therefore, it is essential to understand the molecular markers associated with resistance to these medicines, to aid oncologists in choosing the more effective anti-tumor drugs for patients to achieve the most advantageous potential outcomes.The major molecular markers associated with clinical response to gefitinib or chemotherapy in NSCLC include the status of EGFR, K-RAS mutations and mRNA expression levels of excision repair cross-complementing 1 (ERCC1), class III β-tubulin (TUBB3), thymidylate synthase (TYMS), ribonucleotide reductase subunit M1 (RRM1) and EGFR (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). EGFR is a member of the ErbB family of receptors. Mutations within the tyrosine kinase domain of EGFR account for increased sensitivity to the tyrosine kinase inhibitor (TKIs), such as gefitinib (3,4). However, an insertion mutation and the point mutation T790M in exon 20 of EGFR are associated with resistance to TKIs (5). Previous studies have demonstrated that overexpression of EGFR was associated with increased sensitivity to gefitinib (6,7). K-RAS encodes a small guanosine triphosphate (GTP)-binding protein involved in numerous cellular processes, including proliferation and apoptosis (8). The wild-type K-RAS protein has intrinsic GTPase activity that catalyzes the...

show abstract

Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy

Cited by 60 publications

References 27 publications

MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study

MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study

Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer

EGFR and K-RAS mutations and ERCC1, TUBB3, TYMS, RRM1 and EGFR mRNA expression in non-small cell lung cancer: Correlation with clinical response to gefitinib or chemotherapy

Contact Info

Product

Resources

About