TC-1 (C8orf4) expression is correlated with differentiation in ovarian carcinomas and might distinguish metastatic ovarian from metastatic colorectal carcinomas

Abstract

Thyroid cancer 1 (TC-1, C8orf4) is involved in the development of many cancers. In this study, we investigated the correlation between the expression of TC-1 and the clinicopathological characteristics of ovarian and colorectal adenocarcinomas. We also explored the possible use of TC-1 as a marker to distinguish between metastatic tumors of the ovary and colorectum. We used immunohistochemistry to examine the expression level of TC-1 in 100 ovarian and 100 colorectal adenocarcinomas and 25 metastatic carcinomas with the ovary or colorectum as primary site. TC-1 was expressed in all ovarian carcinoma samples. The high expression rate of TC-1 was 84 % in ovarian carcinomas, which was much higher than that observed in colorectal adenocarcinomas (35 %, P < 0.001). High expression of TC-1 significantly correlated with poor differentiation of ovarian carcinomas (P = 0.013). To explore the value of TC-1 in distinguishing metastatic ovarian cancers from colorectal cancers, we found the area under the receiver operator characteristic curve of TC-1 to be 0.819 (95 % confidence interval, 0.760-0.878; P < 0.001). Furthermore, TC-1 was highly expressed in 100 % of nine metastatic ovarian cancers, but only in 31 % of 16 metastatic colorectal cancers. The higher expression of TC-1 in ovarian compared to colorectal adenocarcinomas suggests its potential use as a marker, to distinguish between metastatic ovarian and colorectal adenocarcinomas.

Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with β-catenin and DNMT1 expression and poor prognosis

“…Although originally identified in papillary thyroid cancer, TC1 is ubiquitously expressed in human tissues [ 2 ]. Studies have shown that TC1 expression levels positively correlates with development of many malignancies including thyroid cancer [ 1 , 17 ], gastric cancer [ 10 ], breast cancer [ 13 ], ovarian carcinomas [ 18 ], oral tongue squamous cell carcinomas [ 19 ], and hematological malignancies [ 20 , 21 ]. Expression levels of TC1 correlate with poor clinical outcome and decreased survival in patients with gastric cancer and hematological malignancies [ 10 , 20 ].…”

Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma

“…Among the 38 genes exclusively expressed in SKOV-3 cells (Supplementary Table S2), ALDH1A1 [26], GABRA3 [27], FOLR1 [28], DPYSL5 [29], CGB8 [30], C8orf4 [31] and MAGEB2 [32] could be intriguing for the development and maintenance of the neoplastic phenotype. Similarly, among the 82 genes expressed only in FT194 cells (Supplementary Table S2) CDKN2A [33], MT1G [34], GPX7 [35], HCK [36], ZBTB16 [37] could be looked at as interesting genes being tumor suppressor epigenetically silenced in cancer cells.…”

Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast

“…Thus yeast is a unique platform that may be useful in delineating the mechanisms by which TC-1 protects cells from stress. This is of potential clinical value since hTC-1 is reported to be transformative and may be a key tumor promoter in certain cancers 51606162. Thus yeast expressing hTC-1 may also serve as a platform to screen for novel inhibitors that may have therapeutic value 39.…”