Strong expression of paired-like homeodomain transcription factor 1 (PITX1) is associated with a favorable outcome in human osteosarcoma

Abstract

Paired-like homeodomain transcription factor 1 (PITX1) has been implicated as a tumor suppressor in various cancers. However, the biological and clinical significance of PITX1 in osteosarcoma has not been fully elucidated. Here, we studied the expression and clinical significance of PITX1 in 6 normal lower limb bone tissue specimens and 35 osteosarcoma tissue samples by immunohistochemistry. PITX1 was expressed in all normal tissues (6/6, 100 %) and in 85.7 % (30/35) of tumor tissues (P > 0.05). In addition, all normal tissue specimens showed high PITX1 expression (6/6, 100 %) while only 23.3 % (7/30) osteosarcoma tissue specimens had high PITX1 expression (P < 0.05). Patients with median overall survival (OS) >12 months had significantly higher PITX1 levels compared with those whose median OS was less than or equal to 12 months (P < 0.05 or 0.001). Furthermore, patients with lung metastasis had significantly lower PITX1 levels than patients without lung metastasis. In conclusion, PITX1 expression is downregulated in osteosarcoma and correlates with patient survival and lung metastasis.

De Novo PITX1 Expression Controls Bi-Stable Transcriptional Circuits to Govern Self-Renewal and Differentiation in Squamous Cell Carcinoma

“…PITX1 function is critical for TPC proliferation and survival, while its decline enables squamous differentiation. Increased PITX1 expression has also been observed in KRAS mutant colorectal cancers (Watanabe et al, 2011) and acute lymphoblastic leukemia (Nagel et al, 2011), while its increased expression correlates with good prognosis in melanoma (Osaki et al, 2013), osteosarcoma (Kong et al, 2015), prostate, lung, liver, and gastric cancers (Calvisi et al, 2011;Chen et al, 2007), indicative of context-dependent functions. Indeed, we found PITX1 cooperates with SOX2 and TRP63 to govern an SCC-specific transcriptional network.…”

Silenced PITX1 promotes chemotherapeutic resistance to 5‑fluorocytosine and cisplatin in gastric cancer cells

“…Furthermore, a decreased PITX1 expression has been revealed in bronchial (17,18), hepatic (19), colorectal (20), pancreatic (21), prostatic (22) and gastric malignancies (15,16). It has also been demonstrated that the level of PITX1 is correlated with patient survival; patients with higher PITX1 levels exhibit a longer median overall survival in human osteosarcoma (24). The reduced expression of PITX1 is also independently correlated with shorter patient survival and may serve as a prognostic marker in colorectal carcinoma (32).…”

“…Various studies have also indicated that PITX1 expression is downregulated in certain types of malignant cancer, including oral squamous cell carcinoma (13), esophageal (14), gastric (15,16), lung (17), breast (18), hepatic (19), colorectal (20), pancreatic (21) and prostatic cancer (22), as well as malignant melanoma (16,23). The strong expression of PITX1 is associated with a favorable outcome in human osteosarcoma (24). PITX1 expression also serves as a novel biomarker for the prediction of patient prognosis in oral epithelial dysplasia (25) and may be a predictive biomarker of human head and neck squamous cell carcinoma chemosensitivity (26).…”

Heritability of Atrial Fibrillation

“…PITX2 is involved in specifying pulmonary venous myocardial sleeves, suppression of a default left-atrial sinus node, and conditional knockout of the Pitx2c transcript has been linked to increased AF susceptibility in mice. 42–44 Activation of PITX1 was suggested to be associated with tumor suppression in various cancers, 45, 46 but the function of PITX1 in cardiac function has not been well-understood. The second novel locus is at 53kb upstream of RASSF8, encoding a candidate tumor suppressor protein, RASSF8 , 47 but the association of RASSF8 and cardiac physiology remains unclear.…”