Department of Otorhinolaryngology Head and Neck Surgery, Medical University of Warsaw, Warsaw, Poland.
Doctoral School, Medical University of Warsaw, Warsaw, Poland.
PeerJ. 2022 Apr 19;10:e13104. doi: 10.7717/peerj.13104. eCollection 2022.
The study was designed to evaluate the potential validity and utility of selected molecular markers in serum samples from patients with specific stages of laryngeal intraepithelial lesions that could serve as diagnostic tools in differentiation of benign and dysplastic lesions from invasive pathologies.
Prospective study included 80 consecutive patients with vocal fold lesions treated at the single otorhinolaryngology centre. All participants had surgical resection of the lesion. Blood samples were collected from each patient before the surgery. Final diagnosis was confirmed on histopathological examination and included 39 (48.75%) non-dysplastic lesions, eight (10%) low-grade dysplasia, six (7.5%) high-grade dysplasia and 27 (33.75%) invasive cancers. The ELISA procedures were performed according to the manufacturer's instruction. Individual serum concentration of selected proteins was reported in ng/ml: Vascular Endothelial-Cadherin Complex (VE-cad), CD44, Human High mobility group protein B1(HMGB1), Kallikrein 6.
The highest mean levels of HMGB1, KLK6 and VE-cad were detected in sera of patients with low-grade dysplasia (81.14, 24.33, 14.17 respectively). Soluble CD44 was the most elevated in patients with non-dysplastic lesions (2.49). The HMGB1, KLK6 and VE-cad serum levels were increasing from non-dysplastic to low-grade dysplasia and followed by the decrease for high-grade dysplasia and invasive cancer, however the differences were not significant (-values 0.897, 0.354, 0.1 respectively). Patients' serum had the highest CD44 concentration in non-dysplastic and low-grade dysplasia with the following decrease through high-grade dysplasia and invasive cancer. GERD symptomatic patients had higher levels of KLK6 and CD44 than other patients (-value 0.06 and 0.084 respectively). There were no significant differences of biomarkers levels related to patients' gender (-value from 0.243 to 1) or smoking status (-value from 0.22 to 0.706).
VE-cad, HMGB1, CD44 and KLK6 did not prove to be reliable biomarkers implicating malignant potential within vocal fold hypertrophic intraepithelial lesions.
本研究旨在评估特定喉内上皮病变阶段患者血清样本中选定分子标志物的潜在有效性和实用性,以期将其作为良性和发育不良病变与侵袭性病变之间的鉴别诊断工具。
前瞻性研究纳入了在单一耳鼻喉科中心接受治疗的 80 例声带病变患者。所有患者均接受了病变的手术切除。每位患者在术前采集了血液样本。最终诊断通过组织病理学检查确认,包括 39 例(48.75%)非发育不良病变、8 例(10%)低级别发育不良、6 例(7.5%)高级别发育不良和 27 例(33.75%)侵袭性癌症。ELISA 程序按照制造商的说明进行。以 ng/ml 报告选定蛋白质的个体血清浓度:血管内皮钙黏蛋白复合物(VE-cad)、CD44、人高迁移率族蛋白 B1(HMGB1)、激肽释放酶 6(Kallikrein 6)。
HMGB1、KLK6 和 VE-cad 的平均水平在低级别发育不良患者的血清中最高(分别为 81.14、24.33 和 14.17)。可溶性 CD44 在非发育不良病变患者中升高最明显(2.49)。HMGB1、KLK6 和 VE-cad 血清水平从非发育不良病变逐渐升高到低级别发育不良,随后在高级别发育不良和侵袭性癌症中降低,但差异无统计学意义(-值分别为 0.897、0.354 和 0.1)。患者血清中非发育不良和低级别发育不良的 CD44 浓度最高,随后在高级别发育不良和侵袭性癌症中降低。胃食管反流病(GERD)症状患者的 KLK6 和 CD44 水平高于其他患者(-值分别为 0.06 和 0.084)。标志物水平与患者性别(-值为 0.243 至 1)或吸烟状况(-值为 0.22 至 0.706)无显著差异。
在声带肥厚性上皮内病变中,VE-cad、HMGB1、CD44 和 KLK6 均不能作为预示恶性潜能的可靠生物标志物。