Preoperative Serum Placenta Growth Factor Level Is a Prognostic Biomarker in Colorectal Cancer

Wei, Shu–Chen; Liang, Jin–Tung; Tsao, Po‐Nien; Hsieh, Fon‐Jou; Yu, Shan–Chi; Wong, Jau‐Min

doi:10.1007/dcr.0b013e3181afbdaf

Cited by 31 publications

(32 citation statements)

References 29 publications

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“…Results linked high circulating PlGF to adverse prognosis in renal (Matsumoto et al 2003) and oral squamous cell carcinoma (Cheng et al 2012) but not in hepatocellular cancer (Nagaoka et al 2010), and high preoperative PlGF levels predicted reduced recurrence-free and overall survival in colorectal cancer patients undergoing curative surgery (Wei et al 2009, Rahbari et al 2011. The latter data fit with our observation that PlGF levels O50th percentile correlated with shorter TTP in the prospective intestinal NET cohort.…”

Section: Discussionsupporting

confidence: 81%

Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

Hilfenhaus¹,

Göhrig²,

Pape³

et al. 2013

Endocrine-Related Cancer

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Placental growth factor (PlGF), a VEGF-homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. Here, we addressed the expression, function, and prognostic value of PlGF in neuroendocrine tumors (NETs). PlGF was determined in NET patients' sera collected retrospectively (n=88) and prospectively (n=87) using Roche-Elecsys and correlated with clinicopathological data. Tumoral PlGF was evaluated by immunohistochemistry, effects of PlGF on proliferation and migration in vitro were assessed using different NET cell lines and effects on tumor growth in vivo in orthotopic xenografts. Circulating and tumoral PlGF was elevated in patients with pancreatic NETs (pNETs) compared with control sera and respective healthy tissue. De novo PlGF expression occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced NET proliferation and migration in vitro and, conversely, neutralizing antibodies to PlGF reduced tumor growth in vivo. Elevated circulating PlGF levels in NET patients correlated with advanced tumor grading and were associated with reduced tumor-related survival in pNETs. Subsequent determinations confirmed and extended our observation of elevated PlGF levels in a prospective cohort of grade 1 and grade 2 pNETs (n=30) and intestinal NETs (n=57). In low-grade pNETs, normal circulating PlGF levels were associated with better survival. In intestinal NETs, circulating PlGF above median emerged as an independent prognostic factor for shorter time-to-progression in multivariate analyses. These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as a prognostic parameter and therapeutic target.

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Section: Discussionsupporting

confidence: 81%

Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

Hilfenhaus¹,

Göhrig²,

Pape³

et al. 2013

Endocrine-Related Cancer

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“…These downstream gene protein products, which in clude VEGF, stromal cell-derived factor 1α (SDF-1α) and PlGF, promote cell survival under hypoxic conditions. Among patients with colorectal cancer, expression of these 4 AMs has been shown to correlate with rates of lymph node or liver metastasis, disease-free survival, and overall survival (17)(18)(19)(20). However, the effects of pre-operative treatment on expression of AMs in rectal cancer remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of stromal cell-derived factor 1α expression is associated with the resistance to neoadjuvant chemoradiotherapy of locally advanced rectal cancer: Angiogenic markers of neoadjuvant chemoradiation

et al. 2014

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Abstract. The ability to achieve pathologic downstaging after neoadjuvant chemoradiotherapy (NCRT) is correlated with improved survival in locally advanced rectal cancer (LARC). However, there is no effective predictive markers. In this study, the expression of angiogenic markers was evaluated in pretreatment biopsies and corresponding post-treatment resection specimens, and were correlated to histopathological tumour characteristics and response. Fifty-five patients with stage II/III rectal cancer treated with 5-fluorouracil (5-FU)-based NCRT were studied. All patients were administered NCRT followed by surgical resection. Immunohistochemical staining for angiogenic markers [hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1α (SDF-1α) and placental growth factor (PlGF)] was performed on specimens obtained before NCRT and after surgery. Expression of VEGF, PlGF and HIF-1α protein was downregulated after NCRT in the rectal cancer tissues (P<0.001, P=0.001 and P=0.044, respectively). However, SDF-1α was upregulated after NCRT (P<0.001). Moreover, upregulated expression of SDF-1α (P=0.016) and positive PlGF staining (P= 0.001) after NCRT were significantly associated with resistance to NCRT. On multivariate analysis, positive PlGF staining after NCRT was found to be independently associated with resistance to NCRT (P=0.013).Our data suggest that SDF-1α and PlGF should be evaluated as new targets for NCRT in LARC.

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“…PlGF stimulates the proliferation of endothelial cells and indirectly upregulates the expression of various proangiogenic factors including VEGFA, FGF2, and PDGFB (29). Previous reports suggested that plasma PlGF levels are upregulated and correlated with survival in various cancers (12)(13)(14). Surprisingly, serum PlGF was found to be more useful than VEGFA in predicting worse prognostic features and survival in patients with operable gastric cancer (14) and hepatocellular cancer (30).…”

Section: Discussionmentioning

confidence: 99%

A new angiogenesis prognostic index with VEGFA, PlGF, and angiopoietin1 predicts survival in patients with advanced gastric cancer

Aktaş

Akbulut²,

Yazıcı³

et al. 2017

Turk J Med Sci

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Background/aim: The role of angiogenic factors in gastric cancer is not clear. We aimed to assess the role of vascular endothelial growth factor A (VEGFA), angiopoietin 1 (Ang-1), and placental growth factor (PlGF) in the prognosis of patients with advanced gastric cancer.Materials and methods: Thirty consecutive patients treated with a modified DCF (docetaxel, cisplatin, and fluorouracil) regimen were included in the study. The plasma VEGFA, Ang-1, and PlGF levels of the patients before treatment and following two cycles of chemotherapy were measured and evaluated as prognostic factors.Results: Poor performance status and lower Ang-1 levels were correlated with poor overall survival (OS). No significant correlation between VEGFA or PlGF and OS was found. An angiogenesis prognostic index (API) based on the levels of VEGFA, Ang-1, and PlGF was found to be highly correlated with OS. Performance status and API were found as independent prognostic factors for OS. Furthermore, a decrease in VEGFA by 25% from the pretreatment level was also found as a prognostic factor for OS independent of response to DCF regimen. Conclusion:Our results support the use of the new API including VEGFA, Ang-1, and PlGF levels in patients with advanced gastric cancer as a predictor of survival.

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Preoperative Serum Placenta Growth Factor Level Is a Prognostic Biomarker in Colorectal Cancer

Abstract: Preoperative serum placenta growth factor levels were higher in patients with colorectal cancer, were negatively correlated with the serum sFlt-1, and could be used as a prognostic indicator for recurrence and survival for colorectal cancer.

Cited by 31 publications

References 29 publications

Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

Upregulation of stromal cell-derived factor 1α expression is associated with the resistance to neoadjuvant chemoradiotherapy of locally advanced rectal cancer: Angiogenic markers of neoadjuvant chemoradiation

A new angiogenesis prognostic index with VEGFA, PlGF, and angiopoietin1 predicts survival in patients with advanced gastric cancer

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