Expression of Placenta Growth Factor (PlGF) in Oral Squamous Cell Carcinomas
Date Issued
2012
Date
2012
Author(s)
Cheng, Shih-Jung
Abstract
Background/Purpose
Placenta growth factor (PlGF) belongs to vascular endothelial growth factor (VEGF) family. PlGF could induce tumor angiogenesis through binding to VEGFR-1, which was highly expressed in a variety of human cancers, including oral cancer. Our previous study demonstrated a significant association of higher expression of PlGF protein with poor prognosis of patients with oral squamous cell carcinoma (OSCC). This study further examined whether the expression of PlGF mRNA in OSCC tissues and the serum PlGF protein level in OSCC patients could be used to predict the progression and prognosis of OSCCs in Taiwan.
Materials and methods
In the first part of this study, we used quantitative real-time reverse transcription-polymerase chain reaction (quantitative RT-PCR) to detect the PlGF mRNA levels in 63 paired OSCC and adjacent normal-looking oral mucosa (non-OSCC) tissues. Threshold cycle (CT) was defined as the PCR cycle number needed to generate a pre-determined amount of DNA (threshold). For a chosen threshold, a smaller starting copy number of mRNA results in a higher CT value. In this study, the relative expression level of tissue PlGF mRNA in each OSCC patient was expressed as -∆CT = – (OSCC CT – non-OSCC CT). Thus, the higher the -∆CT, the greater the copy number of PlGF mRNA in tissues. In the second part of this study, serum samples were obtained from 72 OSCC patients before and 3 months after surgical cancer excision and from 30 normal control subjects. Serum PlGF protein levels were determined by enzyme-linked immunosorbent assay (ELISA).
Results
In the first part of this study, we found that the higher mean PlGF mRNA -∆CT value was significantly associated with OSCCs with larger tumor size (P = 0.03), positive lymph node metastasis (P = 0.003), more advanced clinical stages (P = 0.013) or the presence of loco-regional recurrence (P = 0.039). Positive lymph node metastasis (P = 0.019) and PlGF mRNA -∆CT value > 2 (P = 0.016) were identified as two independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Moreover, Kaplan-Meier curve showed that OSCC patients with a PlGF mRNA -∆CT value > 2 had a significantly poorer recurrence-free survival than those with a PlGF mRNA -∆CT value ≦ 2 (log-rank test, P = 0.017). In the second part of this study, we found that the mean serum PlGF protein levels were significantly higher in pre-surgery OSCC patients than in normal controls (19.1 ± 10.7 pg/ml vs. 10.1 ± 4.5 pg/ml, P < 0.001). Serum PlGF protein levels dropped to near the normal control levels after surgical cancer removal. Higher pre-surgery serum PlGF protein levels were significantly associated with OSCCs with larger tumor size (P = 0.015), positive lymph node metastasis (P = 0.001), more advanced clinical stages (P = 0.002), and loco-regional recurrence (P = 0.037). The serum PlGF protein level was identified as an independent unfavorable prognosis factor by multivariate Cox regression analyses (P = 0.014). Kaplan-Meier curve showed that OSCC patients with a higher serum PlGF protein level had a significantly poorer cumulative recurrence-free survival than those with a lower serum PlGF protein level (log-rank test, P = 0.009). When we used the serum PlGF protein level of 19.1 pg/ml (mean normal control value plus 2 standard deviations) as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence was 80%, 56% and 78%, respectively.
Conclusion
This study found that PlGF mRNA level in OSCC tissues and serum PlGF protein level in OSCC patients could be used to predict the tumor size, regional lymph node metastasis, clinical stage, and recurrence of OSCCs and the prognosis of OSCC patients. Therefore, we conclude that PlGF mRNA level in OSCC tissues and serum PlGF protein level in OSCC patients may be valuable biomarkers for prediction of progression, recurrence and prognosis of OSCC in Taiwan.
Subjects
placenta growth factor
oral cancer
angiogenesis
SDGs
Type
thesis
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