A Keratin 7 and E-Cadherin Signature Is Highly Predictive of Tubo-Ovarian High-Grade Serous Carcinoma Prognosis

Abstract

During tubo-ovarian high-grade serous carcinoma (HGSC) progression, tumoral cells undergo phenotypic changes in their epithelial marker profiles, which are essential for dissemination processes. Here, we set out to determine whether standard epithelial markers can predict HGSC patient prognosis. Levels of E-CADH, KRT7, KRT18, KRT19 were quantified in 18 HGSC cell lines by Western blot and in a Discovery cohort tissue microarray (TMA) (n = 101 patients) using immunofluorescence. E-CADH and KRT7 levels were subsequently analyzed in the TMA of the Canadian Ovarian Experimental Unified Resource cohort (COEUR, n = 1158 patients) and in public datasets. Epithelial marker expression was highly variable in HGSC cell lines and tissues. In the Discovery cohort, high levels of KRT7 and KRT19 were associated with an unfavorable prognosis, whereas high E-CADH expression indicated a better outcome. Expression of KRT7 and E-CADH gave a robust combination to predict overall survival (OS, p = 0.004) and progression free survival (PFS, p = 5.5 × 10−4) by Kaplan–Meier analysis. In the COEUR cohort, the E-CADH-KRT7 signature was a strong independent prognostic biomarker (OS, HR = 1.6, p = 2.9 × 10−4; PFS, HR = 1.3, p = 0.008) and predicted a poor patient response to chemotherapy (p = 1.3 × 10−4). Our results identify a combination of two epithelial markers as highly significant indicators of HGSC patient prognosis and treatment response.

High Keratin-7 Expression in Benign Peri-Tumoral Prostatic Glands Is Predictive of Bone Metastasis Onset and Prostate Cancer-Specific Mortality

“…Antibody specificity was validated and the baseline expression of KRT7 in prostatic cell lines with different species of antibodies (mouse OV-TL 12/30 and rabbit SP52) was determined by Western blot assay on whole-cell extracts ( Supplementary Figure S1A ). Both mouse and rabbit antibodies showed specific and similar bands around the expected 51 kDa molecular weight ( Supplementary Figure S2 ), as previously described [ 18 ]. It was noted that the KRT7 protein level was higher in castration-resistant PC cell lines (DU145, PC3) and non-malignant prostate cell lines (PZ-HPV-7 and RWPE-1) when compared to hormone-sensitive PC cell lines (22Rv1 and LNCaP).…”

“…No previous study had identified KRT7 as a putative prognostic biomarker in PC, and only few conflictual data described an association between the Gleason score and percentage of KRT7 positivity [ 20 , 52 ]. However, its overexpression alone or in combination (E-cadherin) in several other cancer types has been reported to predict a poor prognosis [ 15 , 16 , 17 , 18 ]. On the other hand, high KRT7 expression was associated with a better prognosis in renal cell carcinoma, as an example [ 53 , 54 ].…”

“…It is mainly expressed in glandular epithelia where it exhibits a cytoplasmic pattern. KRT7 is detected in many tissues and its overexpression in tumors was associated with disease progression in several cancer types [ 15 , 16 , 17 , 18 ]. There is no similar data currently available for KRT7 expression in PC.…”

Cancer Progression Gene Expression Profiling Identifies the Urokinase Plasminogen Activator Receptor as a Biomarker of Metastasis in Cutaneous Squamous Cell Carcinoma

“…A closer examination of the clinicopathological characteristics of these specimens found these to be from patients with high-risk features such as either recurrences or PNI. PCA loadings show that the genes exerting the largest effects include MMP1 and MMP10 , KRT7 , and KRT19 ( Figure 3C ), high levels of which in other cancers have been associated with unfavorable prognosis ( 64 ). Another example is SPP1 , which encodes a stromal cell ligand shown to interact with integrin receptors encoded by ITGB1 and ITGA5 , which are both enriched on TSKs ( 9 ).…”

Integrative Multi−Omics Analysis Reveals Candidate Biomarkers for Oral Squamous Cell Carcinoma

“…In addition, the overall survival (OS) effect of hub genes in HNSC was estimated by calculating the log−rank p−value and the hazard ratio (HR). Patients were divided into high (higher than the 75 th percentile) and low (lower than the 25 th percentile) expression groups based on the normalized expression level of the selected gene across all HNSC patients in the database (23). Since there is no OSCC category in both GEPIA and TCGA databases, and OSCC accounts for ~95% of HNSC, we chose HNSC as the category for these validation analyses.…”