Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Turk J Gastroenterol. 2021 Dec;32(12):1049-1056. doi: 10.5152/tjg.2021.20899.
Thrombospondin type 1 domain-containing 7A (THSD7A) has emerged as a new potential molecular tool for multiple tumors since that THSD7A was detected to be expressed in various malignant tumor types including colorectal cancer (CRC). Thus, we investigated the correlation between THSD7A expression and pathologic determinants of azoxymethane (AOM)-induced CRC in a rat model.
A total of 30 rats were included in the study (experimental group; n = 15, control group; n = 15). Azoxymethane was administered to the experimental group weekly as subcutaneous injections at a dose of 15 mg/kg bodyweight for 3 weeks. Five months later, 42 tumors were obtained in the study group and histopathologic evaluation of CRC tumors for THSD7A was performed by immunohistochemical staining. Thrombospondin type 1 domain-containing 7A expression was classified according to staining levels.
While 28.6% of the colonic tumors were stained as negative, mild-moderate and strong staining was determined in 61.9% and 9.5% of the tumors, respectively. Thrombospondin type 1 domain-containing 7A expression levels inversely correlated with Ki-67 expression (P < .001) and tumor grade (P =.02). Receiver operating characteristic analysis showed Ki-67 staining ≥20.5% was determined as a cut-off value for negatively stained THSD7A tumors with 91% sensitivity and 69% specificity (P = .001, area under curve: 0.822). Moreover, higher Ki-67 expression was found to be associated with higher tumor grade (P < .001), presence of lymphatic invasion (P = .003), and higher T stage (P = .003).
Negative staining for THSD7A seems to be linked to invasive pathologic determinants in AOM-induced CRC in rats.
血栓反应蛋白 1 型结构域包含 7A（THSD7A）已成为多种肿瘤的新的潜在分子工具，因为在包括结直肠癌（CRC）在内的各种恶性肿瘤类型中检测到 THSD7A 表达。因此，我们研究了 THSD7A 表达与 AOM 诱导的大鼠 CRC 的病理决定因素之间的相关性。
共有 30 只大鼠纳入研究（实验组，n = 15，对照组，n = 15）。实验组每周给予 AOM 皮下注射，剂量为 15mg/kg 体重，连续 3 周。5 个月后，实验组获得 42 个肿瘤，对 CRC 肿瘤进行 THSD7A 的免疫组织化学染色进行组织病理学评估。根据染色水平对 THSD7A 表达进行分类。
28.6%的结肠肿瘤染色为阴性，61.9%和 9.5%的肿瘤分别为轻度中度和强染色。THSD7A 表达水平与 Ki-67 表达呈负相关（P <.001），与肿瘤分级呈负相关（P =.02）。ROC 分析显示 Ki-67 染色≥20.5%为 THSD7A 阴性肿瘤的截断值，具有 91%的敏感性和 69%的特异性（P =.001，曲线下面积：0.822）。此外，较高的 Ki-67 表达与较高的肿瘤分级（P <.001）、存在淋巴浸润（P =.003）和较高的 T 分期（P =.003）相关。
THSD7A 的阴性染色似乎与 AOM 诱导的大鼠 CRC 中的侵袭性病理决定因素有关。
