| Title |
Elevated expression of podoplanin and its clinicopathological, prognostic, and therapeutic values in squamous non-small cell lung cancer
|
|---|---|
| Published in |
Cancer Management and Research, May 2018
|
| DOI | 10.2147/cmar.s163510 |
| Pubmed ID | |
| Authors |
Liyi Xie, Chen Lin, Qingfu Zhang, Hailan Piao, Darell D Bigner, Zhen Zhang, Xuhui Bao |
| Abstract |
Squamous non-small cell lung cancer (SqNSCLC), as a leading cause of cancer-related deaths worldwide, has limited treatment options and poor prognosis. Thus, novel targeted therapies are desperately needed. SqNSCLC cases from derivation and validation cohorts were ana-lyzed for podoplanin (PDPN) expression, and its clinicopathological correlation and prognostic prediction. The Human Proteome Map database was used to compare the expression of different lung cancer targets in normal human tissues. Two human lung cancer cell lines, H226 (a SqNSCLC line) and A549 (a non-SqNSCLC line), were examined for PDPN expression. The in vitro cytotoxicity of an anti-PDPN therapy (NZ-1-immunotoxin [NZ-1-IT]) was tested against both lines. The in vivo therapeutic effect of NZ-1-IT was examined in subcutaneous non-small cell lung cancer (NSCLC) xenograft mouse models. In the derivation cohort, 40% (28/70) were PDPN positive. There was significantly increasing pleural invasion (46.4% vs 9.5%, p=0.001), lymphovascular invasion (25.0% vs 9.5%, p=0.08), and lymph node involvement (53.6% vs 33.3%, p=0.09) in PDPN-positive vs PDPN-negative patients, along with poorer progression-free survival in PDPN-positive patients (p=0.07). The validation cohort with 224 randomly matched cases from The Cancer Genome Atlas data set also displayed significantly shorter overall survival in the group with elevated PDPN mRNA (p=0.05). However, PDPN showed limited expression in normal tissues. PDPN was highly and specifically expressed on the surface of H226 cells instead of A549 cells. Subsequently, PDPN-positive H226 cells were around 800 times more sensitive to anti-PDPN NZ-1-IT therapy than PDPN-negative A549 cells in vitro. Furthermore, NZ-1-IT significantly delayed tumorigenesis only in the H226 subcutaneous mouse model (p<0.05). Our results demonstrate a distinctively elevated expression of PDPN in SqNSCLC, which is significantly associated with worse clinicopathological features and poorer prognosis. With promising preclinical therapeutic results, anti-PDPN targeted therapy can thus be a robust potential strategy for future SqNSCLC treatment. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 14 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 4 | 29% |
| Student > Ph. D. Student | 1 | 7% |
| Lecturer | 1 | 7% |
| Student > Doctoral Student | 1 | 7% |
| Unknown | 7 | 50% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 36% |
| Biochemistry, Genetics and Molecular Biology | 2 | 14% |
| Unknown | 7 | 50% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 June 2018.
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#18,637,483
of 23,088,369 outputs
Outputs from Cancer Management and Research
#1,056
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#253,020
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Outputs of similar age from Cancer Management and Research
#33
of 61 outputs
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