Transforming Acidic Coiled-coil Protein-3: A Novel Marker for Differential Diagnosis and Prognosis Prediction in Endocervical Adenocarcinoma

Abstract BackgroundEndocervical adenocarcinoma (ECA) is classified as human papilloma virus (HPV)-associated (HPVA) or non-HPVA (NHPVA) type in the International Endocervical Adenocarcinoma Criteria and Classification (IECC). Of them, HPVA is recognized as the representative ECA subtype, which is related to typical molecular characteristics. Transforming acidic coiled-coil protein-3 (TACC3) is an oncogene with frequent abnormal expression, and it also represents a vital biomarker for various human malignancies. This work aimed to examine the role of TACC3 in the diagnosis and prognosis of ECA. MethodsWe analyzed 264 ECA patients who underwent surgical resection, and tumors were classified into HPVA and NHPVA subtypes. The expression levels of TACC3, P16, MLH1, PMS2, MSH2, MSH6, Ki-67 in tumor were evaluated on tissue microarray by immunohistochemistry (IHC). HPV subtypes were detected on formalin-fixed paraffin-embedded (FFPE) ECA tissues by polymerase chain reaction (PCR). ResultsAs suggested by IHC, ECA samples showed increased TACC3 level relative to related non-carcinoma samples. TACC3 expression was also elevated in HPVA compared with NHPA. In HPVA subtype, high TACC3 expression was significantly correlated with P16-positive, Ki-67-high expression. Furthermore, TACC3 level was remarkably related to the histological type (P=0.006), nerve invasion (P=0.003), differentiation (P=0.004), surgical margin (P=0.012), parametrium invasion (P=0.040), Ki-67 (P=0.004) and P16 (P=0.000). Besides, upon Kaplan-Meier analysis, the up-regulated TACC3 was tightly related to the poor overall survival (OS, P= 0.001), disease-free survival (DFS, P< 0.001) as well as recurrence survival (P< 0.001). Moreover, upon multivariate analysis, the elevated TACC3 level served as the marker to independently predict ECA prognosis. ROC curve analyses indicate that TACC3, P16 and HPV subtype showed similar results for distinguishing HPVA from NHPVA, with an area under the ROC curve of 0.640, 0.649 and 0.675, respectively. The combination of TACC3 and HPV subtypes improved diagnostic performance for ECA compared with TACC3, P16 and HPV subtype alone.ConclusionsTaken together, findings in this work reveal that TACC3 may be used as the new biomarker for the diagnosis and prognosis of ECA.