新辅助治疗局部晚期宫颈癌的疗效与 HIF-1α、VEGF-A 和 Ki67 表达的降低有关。
Decreasing expression of HIF-1α, VEGF-A, and Ki67 with efficacy of neoadjuvant therapy in locally advanced cervical cancer.
机构信息
Department of Gynecologic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
出版信息
Medicine (Baltimore). 2023 May 19;102(20):e33820. doi: 10.1097/MD.0000000000033820.
BACKGROUND
Neoadjuvant chemotherapy (NACT) before radical hysterectomy has been widely used for locally advanced cervical cancer (LACC); However, its efficacy is yet to be determined.
METHODS
Effective and predictive biomarkers, which may aid in predicting the chemotherapy responses, were explored in this study. Initially, the expression of HIF-1α, VEGF-A, and Ki67 was detected in 42 paired (pre-NACT and post-NACT) LACC tissues, as well as 40 nonneoplastic cervical epithelial tissues by immunohistochemistry. Then, the correlation of the expression of HIF-1α, VEGF-A, Ki67 with the efficacy of NACT, as well as factors that affect the efficacy of NACT was analyzed.
RESULTS
A clinical response occurred in 66.7% (28/42) of the patients, including 57.1% (16/28) with a complete response and 42.9% (12/28) with a partial response; While 33.33% (14/42) were non-responders, including 42.9% (6/14) with stable disease and 57.1% (8/14) with progressive disease. HIF-1α, VEGF-A, and Ki67 were overexpressed in LACC tissues compared to nonneoplastic tissues (P < .01, respectively); While the expression of HIF-1α, VEGF-A, and Ki67 was significantly decreased after NACT (P < .01, respectively). What's more, in the response group, HIF-1α, VEGF-A, and Ki67 expression were significantly decreased after chemotherapy in the post-chemotherapy cervical cancer tissues compared with the pre-chemotherapy cervical cancer tissues (all P < .05). Additionally, patients with lower histological grade and lower expression of HIF-1α, VEGF-A, and Ki67 were more responsive to NACT (P < .05, respectively); Moreover, the histological grade [P = .025, HR (95% CI): 0.133 (0.023-0.777)], HIF-1α [P = .019, HR (95% CI): 0.599 (0.390-0.918)], and Ki67 [P = .036, HR (95% CI): 0.946 (0898-0.996)] were independent risk factors affecting the efficacy of NACT in LACC.
CONCLUSION
Expression of HIF-1α, VEGF-A, and Ki67 were significantly decreased after NACT, and decreasing expression of HIF-1α, VEGF-A, and Ki67 were related to good response to NACT, suggesting HIF-1α, VEGF-A, and Ki67 may be implicated in evaluating the efficacy of NACT in LACC.
背景
新辅助化疗（NACT）在根治性子宫切除术之前已被广泛用于局部晚期宫颈癌（LACC）；然而，其疗效尚待确定。
方法
本研究旨在探索有效的预测生物标志物，以帮助预测化疗反应。最初，通过免疫组织化学法检测 42 对（术前 NACT 和术后 NACT）LACC 组织和 40 例非肿瘤性宫颈上皮组织中 HIF-1α、VEGF-A 和 Ki67 的表达。然后，分析 HIF-1α、VEGF-A、Ki67 的表达与 NACT 疗效以及影响 NACT 疗效的因素的相关性。
结果
66.7%（28/42）的患者出现临床反应，包括完全缓解 57.1%（16/28）和部分缓解 42.9%（12/28）；33.33%（14/42）为无反应者，包括疾病稳定 42.9%（6/14）和疾病进展 57.1%（8/14）。与非肿瘤组织相比，LACC 组织中 HIF-1α、VEGF-A 和 Ki67 表达过度（P<0.01）；而 NACT 后 HIF-1α、VEGF-A 和 Ki67 的表达明显降低（P<0.01）。更重要的是，在反应组中，与术前宫颈癌组织相比，化疗后宫颈癌组织中 HIF-1α、VEGF-A 和 Ki67 的表达明显降低（均 P<0.05）。此外，组织学分级较低和 HIF-1α、VEGF-A 和 Ki67 表达较低的患者对 NACT 更敏感（均 P<0.05）；此外，组织学分级[P=0.025，HR（95%CI）：0.133（0.023-0.77）]、HIF-1α[P=0.019，HR（95%CI）：0.599（0.390-0.918）]和 Ki67[P=0.036，HR（95%CI）：0.946（0.898-0.996）]是影响 LACC 中 NACT 疗效的独立危险因素。
结论
NACT 后 HIF-1α、VEGF-A 和 Ki67 的表达明显降低，HIF-1α、VEGF-A 和 Ki67 表达降低与 NACT 反应良好相关，提示 HIF-1α、VEGF-A 和 Ki67 可能参与评估 LACC 中 NACT 的疗效。
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