Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Department of Obstetrics and Gynecology, The Second Hospital of Cangnan People's Hospital, Wenzhou 325027, China.
Biosci Rep. 2017 Sep 27;37(5). doi: 10.1042/BSR20170958. Print 2017 Oct 31.
Although galectin-1 and integrin α5β1 confer chemoresistance to certain types of cancer, whether their expression predicts the response to cisplatin-based neoadjuvant chemotherapy (NACT) in squamous cervical cancer remains unclear. Paired tumor samples (pre- and post-chemotherapy) were obtained from 35 bulky squamous cervical cancer patients treated with cisplatin-based NACT and radical hysterectomy at our hospital between January 2007 and August 2014. The expression of galectin-1 and integrin α5β1 in tumor cells and stromal cells was analyzed by immunohistochemistry. The correlation between galectin-1/integrin α5β1 and apoptosis-associated markers was investigated by using the The Cancer Genome Atlas (TCGA) RNA-sequencing data. Seventeen patients were identified as chemotherapy responders and 18 as non-responders. Galectin-1 and integrin α5β1-positive immunostaining was more frequently observed in stromal cells than its in tumor cells. The expression of galectin-1 and integrin α5β1 in stromal and tumor cells was significantly down-regulated in postchemotherapy cervical cancer tissues. High levels of galectin-1 and integrin α5β1 in stromal were associated with a negative chemotherapy response in squamous cervical cancer patients treated with cisplatin-based NACT. Additionally, the expression of galectin-1 and integrin α5 correlated negatively with caspase 3/caspase 8 by using the TCGA RNA-sequencing data. Galectin-1 and integrin α5β1 expression in stromal may serve as a prediction of the responses to cisplatin-based NACT for patients with bulky squamous cervical cancer. Galectin-1 and integrin α5β1 may be implicated in the development of chemoresistance in cervical cancer via suppressing apoptosis.
尽管半乳糖凝集素-1 和整合素 α5β1 赋予某些类型的癌症对化疗药物的耐药性,但它们的表达是否能预测宫颈癌患者接受顺铂为基础的新辅助化疗(NACT)的反应仍不清楚。我们从 2007 年 1 月至 2014 年 8 月在我院接受以顺铂为基础的 NACT 和根治性子宫切除术治疗的 35 例大体积宫颈鳞癌患者中获得了配对的肿瘤样本(化疗前和化疗后)。通过免疫组织化学分析肿瘤细胞和基质细胞中半乳糖凝集素-1 和整合素 α5β1 的表达。通过使用癌症基因组图谱(TCGA)RNA 测序数据研究半乳糖凝集素-1/整合素 α5β1 与凋亡相关标志物之间的相关性。鉴定出 17 例患者为化疗应答者,18 例患者为非应答者。半乳糖凝集素-1 和整合素 α5β1 的阳性免疫染色在基质细胞中比在肿瘤细胞中更常见。化疗后宫颈癌组织中半乳糖凝集素-1 和整合素 α5β1 的表达在基质和肿瘤细胞中均显著下调。在接受顺铂为基础的 NACT 的宫颈鳞癌患者中,基质中高表达的半乳糖凝集素-1 和整合素 α5β1 与化疗反应阴性相关。此外,使用 TCGA RNA 测序数据表明,半乳糖凝集素-1 和整合素 α5 的表达与 caspase3/caspase8 呈负相关。基质中半乳糖凝集素-1 和整合素 α5β1 的表达可能可作为预测接受顺铂为基础的 NACT 的大体积宫颈鳞癌患者反应的指标。半乳糖凝集素-1 和整合素 α5β1 可能通过抑制凋亡参与宫颈癌的化疗耐药性的发展。