Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan.
Department of General Internal Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
Ann Surg Oncol. 2024 Jan;31(1):251-261. doi: 10.1245/s10434-023-14364-9. Epub 2023 Oct 5.
Preoperative chemotherapy/chemoradiotherapy has been generally considered for the treatment of esophageal squamous cell carcinoma (ESCC) to improve prognosis. We examined the effects of anticancer drugs on the expression of kallikrein-related peptidase 13 (KLK13), a potential ESCC prognostic marker, and its clinical relevance in patients who received chemotherapy/chemoradiotherapy for ESCC.
Overall, 105 patients with ESCC who received chemotherapy or chemoradiotherapy before esophagectomy were enrolled. The expression of KLK13 in biopsy samples obtained before chemotherapy/chemoradiotherapy and resected ESCC tumors was assessed by immunohistochemical staining. The effects of 5-fluorouracil (5-FU) and/or cisplatin (CDDP) exposure on the expressions of KLK13 and ten-eleven translocation dioxygenases (TET) in ESCC cells were examined by reverse transcription-polymerase chain reaction.
Immunohistochemical staining of paired ESCC specimens before (biopsy samples) and after (resected specimens) chemotherapy/chemoradiotherapy demonstrated a change in KLK13 expression. KLK13 and TET2/3 transcriptions were induced when human ESCC cell lines were treated with 5-FU and/or CDDP. Among patients with KLK13-negative status before chemotherapy/chemoradiotherapy, those with KLK13-positive resected tumors had a significantly poorer prognosis than those with KLK13-negative resected tumors (p = 0.0477). By using tumor cells isolated from ESCC biopsy tissues obtained before chemotherapy/chemoradiotherapy, we established a primary culture system and detected the induction of KLK13 expression by anticancer drugs.
Preoperative treatments alter KLK13 expression in ESCC. The conversion of KLK13 expression from a negative status in biopsy samples to a positive status in resected tumor samples is a predictor of poor prognosis. KLK13 status is a potential marker for decision making to avoid harmful chemotherapy/chemoradiotherapy in patients with ESCC.
术前化疗/放化疗通常被认为是治疗食管鳞癌（ESCC）的一种方法，可以改善预后。我们研究了抗癌药物对激肽释放酶相关肽酶 13（KLK13）表达的影响，KLK13 是一种潜在的 ESCC 预后标志物，并在接受 ESCC 化疗/放化疗的患者中研究了其临床相关性。
共纳入 105 例接受术前化疗或放化疗的 ESCC 患者。通过免疫组织化学染色评估化疗/放化疗前活检样本和切除的 ESCC 肿瘤中 KLK13 的表达。通过逆转录聚合酶链反应（RT-PCR）检测 5-氟尿嘧啶（5-FU）和/或顺铂（CDDP）暴露对 ESCC 细胞中 KLK13 和 ten-eleven translocation dioxygenases（TET）表达的影响。
对化疗/放化疗前后（活检样本和切除样本）配对的 ESCC 标本进行免疫组织化学染色显示 KLK13 表达发生变化。当人 ESCC 细胞系用 5-FU 和/或 CDDP 处理时，KLK13 和 TET2/3 转录物被诱导。在化疗/放化疗前 KLK13 阴性的患者中，KLK13 阳性切除肿瘤的患者预后明显差于 KLK13 阴性切除肿瘤的患者（p=0.0477）。通过使用化疗/放化疗前获得的 ESCC 活检组织中的肿瘤细胞，我们建立了一个原代培养系统，并检测了抗癌药物诱导 KLK13 表达的情况。
术前治疗改变了 ESCC 中的 KLK13 表达。KLK13 表达从活检样本中的阴性状态转变为切除肿瘤样本中的阳性状态是预后不良的预测指标。KLK13 状态是决定是否避免对 ESCC 患者进行有害的化疗/放化疗的潜在标志物。
