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The expression levels of CYP3A4 and CYP3A5 serve as potential prognostic biomarkers in lung adenocarcinoma.

Abstract Lung adenocarcinoma remains to be a high-mortality disease with few effective prognostic biomarkers. Novel biomarkers are urgently demanded to supplement the current prognostic biomarkers. Here, we explored the prognostic value of CYP3A4 and CYP3A5 in lung adenocarcinoma. The tissue microarray was made up of lung adenocarcinoma samples and corresponding normal lung tissues from Nanjing Medical University affiliated Cancer Hospital Tissue Bank. The expression of CYP3A4, together with CYP3A5, was detected by the chip data from Gene Expression Omnibus datasets and immunohistochemistry staining of the tissue microarray. Then, we assessed the relationships between CYP3A4 or CYP3A5 expression level and clinicopathological factors to estimate the clinical significance. Kaplan-Meier curves were applied to analyze the prognosis. Univariate and multivariate Cox analyses were subsequently applied to identify the independent prognostic factors. Immunohistochemistry staining results showed that by comparison with matched normal tissues, CYP3A4 was frequently hyper-expressed in lung adenocarcinoma tissues while CYP3A5 was hypo-expressed, which was consistent with the Gene Expression Omnibus analysis. Kaplan-Meier analysis indicated that high-CYP3A4 or low-CYP3A5 expression level predicted poor survival in lung adenocarcinoma patients. Multivariate Cox analysis found that hypo-expression of CYP3A5 was an independent prognostic factor. Further study revealed that combination of these two markers exhibited a more powerful predictor of poor prognosis, which could target to more accurate survival of lung adenocarcinoma. Our findings indicate that combination of CYP3A4 and CYP3A5 may serve as a novel prognostic biomarker in lung adenocarcinoma, which contribute to the precision of predicting the survival in lung adenocarcinoma.
PMID
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Authors

Mayor MeshTerms
Keywords

CYP3A4

CYP3A5

lung adenocarcinoma

prognostic biomarker

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28381170
OWN - NLM
STAT- MEDLINE
DA  - 20170406
DCOM- 20170418
LR  - 20170418
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 4
DP  - 2017 Apr
TI  - The expression levels of CYP3A4 and CYP3A5 serve as potential prognostic
      biomarkers in lung adenocarcinoma.
PG  - 1010428317698340
LID - 10.1177/1010428317698340 [doi]
AB  - Lung adenocarcinoma remains to be a high-mortality disease with few effective
      prognostic biomarkers. Novel biomarkers are urgently demanded to supplement the
      current prognostic biomarkers. Here, we explored the prognostic value of CYP3A4
      and CYP3A5 in lung adenocarcinoma. The tissue microarray was made up of lung
      adenocarcinoma samples and corresponding normal lung tissues from Nanjing Medical
      University affiliated Cancer Hospital Tissue Bank. The expression of CYP3A4,
      together with CYP3A5, was detected by the chip data from Gene Expression Omnibus 
      datasets and immunohistochemistry staining of the tissue microarray. Then, we
      assessed the relationships between CYP3A4 or CYP3A5 expression level and
      clinicopathological factors to estimate the clinical significance. Kaplan-Meier
      curves were applied to analyze the prognosis. Univariate and multivariate Cox
      analyses were subsequently applied to identify the independent prognostic
      factors. Immunohistochemistry staining results showed that by comparison with
      matched normal tissues, CYP3A4 was frequently hyper-expressed in lung
      adenocarcinoma tissues while CYP3A5 was hypo-expressed, which was consistent with
      the Gene Expression Omnibus analysis. Kaplan-Meier analysis indicated that
      high-CYP3A4 or low-CYP3A5 expression level predicted poor survival in lung
      adenocarcinoma patients. Multivariate Cox analysis found that hypo-expression of 
      CYP3A5 was an independent prognostic factor. Further study revealed that
      combination of these two markers exhibited a more powerful predictor of poor
      prognosis, which could target to more accurate survival of lung adenocarcinoma.
      Our findings indicate that combination of CYP3A4 and CYP3A5 may serve as a novel 
      prognostic biomarker in lung adenocarcinoma, which contribute to the precision of
      predicting the survival in lung adenocarcinoma.
FAU - Qixing, Mao
AU  - Qixing M
AD  - 1 Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of
      Cancer research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 
      China.
AD  - 2 The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
AD  - 3 Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer
      Institute of Jiangsu Province, Nanjing, China.
FAU - Juqing, Xu
AU  - Juqing X
AD  - 4 Department of Oncology, Jiangsu Province Geriatric Hospital, Nanjing, China.
FAU - Yajing, Wang
AU  - Yajing W
AD  - 5 Nanjing Medical University, Nanjing, China.
FAU - Gaochao, Dong
AU  - Gaochao D
AD  - 1 Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of
      Cancer research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 
      China.
AD  - 3 Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer
      Institute of Jiangsu Province, Nanjing, China.
FAU - Wenjie, Xia
AU  - Wenjie X
AD  - 1 Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of
      Cancer research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 
      China.
AD  - 2 The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
AD  - 3 Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer
      Institute of Jiangsu Province, Nanjing, China.
FAU - Run, Shi
AU  - Run S
AD  - 1 Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of
      Cancer research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 
      China.
AD  - 2 The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
AD  - 3 Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer
      Institute of Jiangsu Province, Nanjing, China.
FAU - Anpeng, Wang
AU  - Anpeng W
AD  - 1 Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of
      Cancer research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 
      China.
AD  - 2 The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
AD  - 3 Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer
      Institute of Jiangsu Province, Nanjing, China.
FAU - Lin, Xu
AU  - Lin X
AD  - 1 Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of
      Cancer research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 
      China.
AD  - 3 Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer
      Institute of Jiangsu Province, Nanjing, China.
FAU - Feng, Jiang
AU  - Feng J
AD  - 1 Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of
      Cancer research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 
      China.
AD  - 3 Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer
      Institute of Jiangsu Province, Nanjing, China.
FAU - Jun, Wang
AU  - Jun W
AD  - 4 Department of Oncology, Jiangsu Province Geriatric Hospital, Nanjing, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Biomarkers, Tumor)
RN  - EC 1.14.13.67 (CYP3A4 protein, human)
RN  - EC 1.14.14.1 (CYP3A5 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - Adenocarcinoma of lung
SB  - IM
MH  - Adenocarcinoma/*enzymology/mortality/pathology
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/analysis
MH  - Cytochrome P-450 CYP3A/*analysis
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*enzymology/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Proportional Hazards Models
OTO - NOTNLM
OT  - CYP3A4
OT  - CYP3A5
OT  - lung adenocarcinoma
OT  - prognostic biomarker
EDAT- 2017/04/07 06:00
MHDA- 2017/04/19 06:00
CRDT- 2017/04/07 06:00
AID - 10.1177/1010428317698340 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Apr;39(4):1010428317698340. doi: 10.1177/1010428317698340.

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