Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer

Masafumi Takeshita, Takaomi Koga, Koichi Takayama, Tokujiro Yano, Yoshihiko Maehara, Yoichi Nakanishi, Katsuo Sueishi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Experiments using cancer cell lines have revealed that CHFR methylation correlates with sensitivity to microtubule inhibitors. However, this marker may not benefit actual clinical cases because it is difficult to detect CHFR methylation without surgically resected samples. Thus, a more easily accessible marker that correlates with sensitivity to microtubule inhibitors might be useful in NSCLC, especially in advanced cases. In this study, we show that EGFR gene status and smoking are predict the efficacy of treatment with microtubule inhibitors in NSCLC. Chemosensitivity to paclitaxel and six other chemotherapeutic agents was evaluated using the succinate dehydrogenase inhibition (SDI) method in 69 NSCLC cases, consisting of 48 adenocarcinomas, 20 squamous cell carcinomas and 1 large cell carcinoma. Next, we evaluated the relationships between CHFR or EGFR status and clinicopathologic data. Methylation-specific PCR (MSP ) and direct DNA sequencing were performed to detect aberrant methylation of CHFR and EGFR mutations, respectively. CHFR gene promoter methylation and EGFR gene mutation were observed in 11 cases (15.9%) and 7 cases (10.1%), respectively. The SDI method revealed that CHFR gene methylation was significantly related to high sensitivity to paclitaxel (p<0.001), while no sensitivity was found to other agents. Interestingly, sensitivity to paclitaxel also correlated with wild type EGFR genotype (p=0.014) and patients with a smoking habit (0.029). Our results demonstrate that a wild-type EGFR genotype and a smoking habit, in addition to aberrant methylation of the CHFR gene, might be a predictor of clinical response to paclitaxel in NSCLC.

Original languageEnglish
Pages (from-to)933-941
Number of pages9
JournalCancer Biology and Therapy
Volume10
Issue number9
DOIs
Publication statusPublished - Nov 1 2010

Fingerprint

Paclitaxel
Non-Small Cell Lung Carcinoma
Methylation
Microtubules
erbB-1 Genes
Succinate Dehydrogenase
Smoking
Habits
Genotype
Genes
Large Cell Carcinoma
Mutation
DNA Sequence Analysis
Squamous Cell Carcinoma
Adenocarcinoma
Cell Line
Polymerase Chain Reaction
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Takeshita, M., Koga, T., Takayama, K., Yano, T., Maehara, Y., Nakanishi, Y., & Sueishi, K. (2010). Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer. Cancer Biology and Therapy, 10(9), 933-941. https://doi.org/10.4161/cbt.10.9.13320

Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer. / Takeshita, Masafumi; Koga, Takaomi; Takayama, Koichi; Yano, Tokujiro; Maehara, Yoshihiko; Nakanishi, Yoichi; Sueishi, Katsuo.

In: Cancer Biology and Therapy, Vol. 10, No. 9, 01.11.2010, p. 933-941.

Research output: Contribution to journalArticle

Takeshita, M, Koga, T, Takayama, K, Yano, T, Maehara, Y, Nakanishi, Y & Sueishi, K 2010, 'Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer', Cancer Biology and Therapy, vol. 10, no. 9, pp. 933-941. https://doi.org/10.4161/cbt.10.9.13320
Takeshita, Masafumi ; Koga, Takaomi ; Takayama, Koichi ; Yano, Tokujiro ; Maehara, Yoshihiko ; Nakanishi, Yoichi ; Sueishi, Katsuo. / Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer. In: Cancer Biology and Therapy. 2010 ; Vol. 10, No. 9. pp. 933-941.
@article{aa9b6af396c34a0ea58b1321264be2a0,
title = "Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer",
abstract = "Experiments using cancer cell lines have revealed that CHFR methylation correlates with sensitivity to microtubule inhibitors. However, this marker may not benefit actual clinical cases because it is difficult to detect CHFR methylation without surgically resected samples. Thus, a more easily accessible marker that correlates with sensitivity to microtubule inhibitors might be useful in NSCLC, especially in advanced cases. In this study, we show that EGFR gene status and smoking are predict the efficacy of treatment with microtubule inhibitors in NSCLC. Chemosensitivity to paclitaxel and six other chemotherapeutic agents was evaluated using the succinate dehydrogenase inhibition (SDI) method in 69 NSCLC cases, consisting of 48 adenocarcinomas, 20 squamous cell carcinomas and 1 large cell carcinoma. Next, we evaluated the relationships between CHFR or EGFR status and clinicopathologic data. Methylation-specific PCR (MSP ) and direct DNA sequencing were performed to detect aberrant methylation of CHFR and EGFR mutations, respectively. CHFR gene promoter methylation and EGFR gene mutation were observed in 11 cases (15.9{\%}) and 7 cases (10.1{\%}), respectively. The SDI method revealed that CHFR gene methylation was significantly related to high sensitivity to paclitaxel (p<0.001), while no sensitivity was found to other agents. Interestingly, sensitivity to paclitaxel also correlated with wild type EGFR genotype (p=0.014) and patients with a smoking habit (0.029). Our results demonstrate that a wild-type EGFR genotype and a smoking habit, in addition to aberrant methylation of the CHFR gene, might be a predictor of clinical response to paclitaxel in NSCLC.",
author = "Masafumi Takeshita and Takaomi Koga and Koichi Takayama and Tokujiro Yano and Yoshihiko Maehara and Yoichi Nakanishi and Katsuo Sueishi",
year = "2010",
month = "11",
day = "1",
doi = "10.4161/cbt.10.9.13320",
language = "English",
volume = "10",
pages = "933--941",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "9",

}

TY - JOUR

T1 - Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer

AU - Takeshita, Masafumi

AU - Koga, Takaomi

AU - Takayama, Koichi

AU - Yano, Tokujiro

AU - Maehara, Yoshihiko

AU - Nakanishi, Yoichi

AU - Sueishi, Katsuo

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Experiments using cancer cell lines have revealed that CHFR methylation correlates with sensitivity to microtubule inhibitors. However, this marker may not benefit actual clinical cases because it is difficult to detect CHFR methylation without surgically resected samples. Thus, a more easily accessible marker that correlates with sensitivity to microtubule inhibitors might be useful in NSCLC, especially in advanced cases. In this study, we show that EGFR gene status and smoking are predict the efficacy of treatment with microtubule inhibitors in NSCLC. Chemosensitivity to paclitaxel and six other chemotherapeutic agents was evaluated using the succinate dehydrogenase inhibition (SDI) method in 69 NSCLC cases, consisting of 48 adenocarcinomas, 20 squamous cell carcinomas and 1 large cell carcinoma. Next, we evaluated the relationships between CHFR or EGFR status and clinicopathologic data. Methylation-specific PCR (MSP ) and direct DNA sequencing were performed to detect aberrant methylation of CHFR and EGFR mutations, respectively. CHFR gene promoter methylation and EGFR gene mutation were observed in 11 cases (15.9%) and 7 cases (10.1%), respectively. The SDI method revealed that CHFR gene methylation was significantly related to high sensitivity to paclitaxel (p<0.001), while no sensitivity was found to other agents. Interestingly, sensitivity to paclitaxel also correlated with wild type EGFR genotype (p=0.014) and patients with a smoking habit (0.029). Our results demonstrate that a wild-type EGFR genotype and a smoking habit, in addition to aberrant methylation of the CHFR gene, might be a predictor of clinical response to paclitaxel in NSCLC.

AB - Experiments using cancer cell lines have revealed that CHFR methylation correlates with sensitivity to microtubule inhibitors. However, this marker may not benefit actual clinical cases because it is difficult to detect CHFR methylation without surgically resected samples. Thus, a more easily accessible marker that correlates with sensitivity to microtubule inhibitors might be useful in NSCLC, especially in advanced cases. In this study, we show that EGFR gene status and smoking are predict the efficacy of treatment with microtubule inhibitors in NSCLC. Chemosensitivity to paclitaxel and six other chemotherapeutic agents was evaluated using the succinate dehydrogenase inhibition (SDI) method in 69 NSCLC cases, consisting of 48 adenocarcinomas, 20 squamous cell carcinomas and 1 large cell carcinoma. Next, we evaluated the relationships between CHFR or EGFR status and clinicopathologic data. Methylation-specific PCR (MSP ) and direct DNA sequencing were performed to detect aberrant methylation of CHFR and EGFR mutations, respectively. CHFR gene promoter methylation and EGFR gene mutation were observed in 11 cases (15.9%) and 7 cases (10.1%), respectively. The SDI method revealed that CHFR gene methylation was significantly related to high sensitivity to paclitaxel (p<0.001), while no sensitivity was found to other agents. Interestingly, sensitivity to paclitaxel also correlated with wild type EGFR genotype (p=0.014) and patients with a smoking habit (0.029). Our results demonstrate that a wild-type EGFR genotype and a smoking habit, in addition to aberrant methylation of the CHFR gene, might be a predictor of clinical response to paclitaxel in NSCLC.

UR - http://www.scopus.com/inward/record.url?scp=78549282146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78549282146&partnerID=8YFLogxK

U2 - 10.4161/cbt.10.9.13320

DO - 10.4161/cbt.10.9.13320

M3 - Article

C2 - 20855974

AN - SCOPUS:78549282146

VL - 10

SP - 933

EP - 941

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 9

ER -