Abstract
We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC) tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.
Highlights
Endometrial cancer (EC) is the most common gynecologic malignancy and the fourth most common cancer in females, ranking behind breast, lung and colorectal cancers in the United States.While early stage endometrial cancer (EC) has a favorable prognosis, late stage EC is associated with a relatively high rate of post-treatment recurrence and mortality
HE4 Protein Is Overexpressed in Endometrial Cancer
Utilization of alternative splicing or alternative promoters allows a single gene to encode multiple structurally and functionally related proteins. These processes have greatly increased the diversity of proteome, and may constitute an effective and economical mechanism for fine-tuned regulations of cell functions
Summary
Endometrial cancer (EC) is the most common gynecologic malignancy and the fourth most common cancer in females, ranking behind breast, lung and colorectal cancers in the United States.While early stage EC has a favorable prognosis, late stage EC is associated with a relatively high rate of post-treatment recurrence and mortality. Bingle et al used Northern blot hybridization in order to characterize its tissue-specific expression and found that HE4 mRNA is abundant in lung, kidney, and the salivary gland [8]. Lu et al performed oligo-array analysis and observed that HE4 is overexpressed in OC in comparison to normal ovarian epithelium [10]. Drs Drapkin and Galgano et al analyzed the expression of HE4 in a series of normal and malignant tissues and observed high levels of HE4 mRNA in the trachea and salivary gland [11,12]. Tissue microarray studies indicate that HE4 protein is present in both normal and malignant ovarian and endometrial cells [10,11,12,13]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call