Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer.
Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer.
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DOI：
10.1097/js9.0000000000000200
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发表时间：
2023-02-01
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新辅助治疗（NAT）越来越多地应用于胰腺导管腺癌（PDAC）;然而，准确预测NAT的治疗反应仍然是一个紧迫的临床挑战。癌细胞来源的唾液酸化免疫球蛋白G（SIA-IgG）先前被确定为PDAC中的预后生物标志物。本研究旨在探讨未经治疗的细针穿刺（FNA）活检标本中的SIA-IgG表达是否可以预测PDAC对NAT的病理学反应（PR）。在NAT之前，从约翰霍普金斯医院的72例PDAC患者中前瞻性地获得了内镜超声引导的FNA活检标本。免疫组化法检测PDAC标本中SIA-IgG的表达。分析SIA-IgG表达与PR以及患者预后之间的关系。第二个队列招募了来自79名PDAC患者的手术切除的原发性肿瘤标本，用于验证SIA-IgG表达的预后价值。SIA-IgG在58.3%的未经治疗的FNA活检中表达。诊断时SIA-IgG阳性表达与PR不利相关，可作为PR的独立预测因子，FNA标本SIA-IgG表达预测PR不利的敏感性和特异性分别为63.9%和80.6%。未经治疗的FNA标本中SIA-IgG阳性表达和手术切除的原发性肿瘤标本中SIA-IgG高表达均与较短的生存期显著相关。NAT前评估FNA标本上的SIA-IgG可能有助于预测PDAC的PR。此外，SIA-IgG在未经治疗的FNA标本和手术切除的原发性肿瘤标本中的表达可预测PDAC的预后。
Neoadjuvant therapy (NAT) is increasingly applied in pancreatic ductal adenocarcinoma (PDAC); however, accurate prediction of therapeutic response to NAT remains a pressing clinical challenge. Cancer-cell-derived sialylated immunoglobulin G (SIA-IgG) was previously identified as a prognostic biomarker in PDAC. This study aims to explore whether SIA-IgG expression in treatment-naïve fine needle aspirate (FNA) biopsy specimens could predict the pathological response (PR) to NAT for PDAC. Endoscopic ultrasonography-guided FNA biopsy specimens prior to NAT were prospectively obtained from 72 patients with PDAC at the Johns Hopkins Hospital. SIA-IgG expression of PDAC specimens was assessed by immunohistochemistry. Associations between SIA-IgG expression and PR, as well as patient prognosis, were analyzed. A second cohort enrolling surgically resected primary tumor specimens from 79 patients with PDAC was used to validate the prognostic value of SIA-IgG expression. SIA-IgG was expressed in 58.3% of treatment-naïve FNA biopsies. Positive SIA-IgG expression at diagnosis was associated with unfavorable PR and can serve as an independent predictor of PR. The sensitivity and specificity of SIA-IgG expression in FNA specimens in predicting an unfavorable PR were 63.9% and 80.6%, respectively. Both positive SIA-IgG expression in treatment-naïve FNA specimens and high SIA-IgG expression in surgically resected primary tumor specimens were significantly associated with shorter survival. Assessment of SIA-IgG on FNA specimens prior to NAT may help predict PR for PDAC. Additionally, SIA-IgG expression in treatment-naïve FNA specimens and surgically resected primary tumor specimens were predictive of the prognosis for PDAC.