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HIF-2α not HIF-1α overexpression confers poor prognosis in non-small cell lung cancer.

Abstract HIF-α may play an important role in the process of tumorigenesis as well as tumor progression. Although a number of investigations have established the significance of HIF-1α in several human tumors, there is still little information available on the clinical significance of HIF-2α expression in non-small cell lung cancer (NSCLC). In present study, immunohistologic expression of HIF-1α/ HIF-2α was studied in a tissue microarray of 140 Stage I-III NSCLCs and correlated with clinicopathologic parameters and clinical outcome. We found that HIF-1α/ HIF-2α showed a cytoplasmic pattern of expression in tumor cells while normal lung components showed negative or weak cytoplasmic staining. High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases respectively. There was no direct correlation between HIF-1α and HIF-2α expression ( p = 0.200). The high HIF-2α expression was associated with histology (squamous cell carcinoma vs. adenocarcinomas) in these patients ( p = 0.001). Patients in advanced tumor stage had frequent high expression of HIF-2α ( p = 0.007), and the similar high expression was also observed in advanced T or N stage ( p = 0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage ( p = 0.084), which showed a higher expression in early tumor stage. Univariate analysis of the overall survival demonstrates that HIF-2α expression but not HIF-1α was related to poor outcome ( p = 0.005) and it retained significance in multivariate analysis ( p = 0.046). In conclusion, HIF-2α expression was related to tumor size, lymph node metastasis, tumor stage and histology. We also found a positive prognostic value of HIF-2α protein expression. HIF-2α might serve as a potential prognosis biomarker in evaluating progression and prognosis of NSCLC. We believe that our study will be of great benefit to the clinical treatment and prognostic evaluation of NSCLC.
PMID
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Authors

Mayor MeshTerms

Prognosis

Keywords

HIF-1α/2α

Non–small cell lung cancer

immunohistochemistry

prognostic factor

tissue microarray

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




PMID- 28653893
OWN - NLM
STAT- MEDLINE
DA  - 20170627
DCOM- 20170711
LR  - 20170713
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 6
DP  - 2017 Jun
TI  - HIF-2alpha not HIF-1alpha overexpression confers poor prognosis in non-small cell
      lung cancer.
PG  - 1010428317709637
LID - 10.1177/1010428317709637 [doi]
AB  - HIF-alpha may play an important role in the process of tumorigenesis as well as
      tumor progression. Although a number of investigations have established the
      significance of HIF-1alpha in several human tumors, there is still little
      information available on the clinical significance of HIF-2alpha expression in
      non-small cell lung cancer (NSCLC). In present study, immunohistologic expression
      of HIF-1alpha/ HIF-2alpha was studied in a tissue microarray of 140 Stage I-III
      NSCLCs and correlated with clinicopathologic parameters and clinical outcome. We 
      found that HIF-1alpha/ HIF-2alpha showed a cytoplasmic pattern of expression in
      tumor cells while normal lung components showed negative or weak cytoplasmic
      staining. High HIF-1alpha and HIF-2alpha expression was noted in 49/140 (35.0%)
      and in 64/140 (45.7%) of the cases respectively. There was no direct correlation 
      between HIF-1alpha and HIF-2alpha expression ( p = 0.200). The high HIF-2alpha
      expression was associated with histology (squamous cell carcinoma vs.
      adenocarcinomas) in these patients ( p = 0.001). Patients in advanced tumor stage
      had frequent high expression of HIF-2alpha ( p = 0.007), and the similar high
      expression was also observed in advanced T or N stage ( p = 0.030 and 0.043,
      respectively). HIF-1alpha showed a marginal association with T stage ( p =
      0.084), which showed a higher expression in early tumor stage. Univariate
      analysis of the overall survival demonstrates that HIF-2alpha expression but not 
      HIF-1alpha was related to poor outcome ( p = 0.005) and it retained significance 
      in multivariate analysis ( p = 0.046). In conclusion, HIF-2alpha expression was
      related to tumor size, lymph node metastasis, tumor stage and histology. We also 
      found a positive prognostic value of HIF-2alpha protein expression. HIF-2alpha
      might serve as a potential prognosis biomarker in evaluating progression and
      prognosis of NSCLC. We believe that our study will be of great benefit to the
      clinical treatment and prognostic evaluation of NSCLC.
FAU - Gao, Zhao-Jia
AU  - Gao ZJ
AD  - 1 Division of Thoracic Surgery, Changzhou No. 2 People's Hospital, Nanjing
      Medical University, Changzhou, China.
AD  - 2 Heart and Lung Disease Laboratory, Changzhou No. 2 People's Hospital, Nanjing
      Medical University, Changzhou, China.
FAU - Wang, Yong
AU  - Wang Y
AD  - 1 Division of Thoracic Surgery, Changzhou No. 2 People's Hospital, Nanjing
      Medical University, Changzhou, China.
FAU - Yuan, Wei-Dong
AU  - Yuan WD
AD  - 1 Division of Thoracic Surgery, Changzhou No. 2 People's Hospital, Nanjing
      Medical University, Changzhou, China.
FAU - Yuan, Jun-Qiang
AU  - Yuan JQ
AD  - 1 Division of Thoracic Surgery, Changzhou No. 2 People's Hospital, Nanjing
      Medical University, Changzhou, China.
FAU - Yuan, Kai
AU  - Yuan K
AD  - 1 Division of Thoracic Surgery, Changzhou No. 2 People's Hospital, Nanjing
      Medical University, Changzhou, China.
AD  - 2 Heart and Lung Disease Laboratory, Changzhou No. 2 People's Hospital, Nanjing
      Medical University, Changzhou, 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 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (endothelial PAS domain-containing protein 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Basic Helix-Loop-Helix Transcription Factors/*biosynthesis/genetics
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis/genetics
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Neovascularization, Pathologic/genetics/pathology
MH  - *Prognosis
MH  - Tissue Array Analysis
OTO - NOTNLM
OT  - HIF-1alpha/2alpha
OT  - Non-small cell lung cancer
OT  - immunohistochemistry
OT  - prognostic factor
OT  - tissue microarray
EDAT- 2017/06/28 06:00
MHDA- 2017/07/14 06:00
CRDT- 2017/06/28 06:00
AID - 10.1177/1010428317709637 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Jun;39(6):1010428317709637. doi: 10.1177/1010428317709637.