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. 2023 Feb 1;109(2):99-106.
doi: 10.1097/JS9.0000000000000200.

Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer

Ming Cui  1   2 , Sami Shoucair  3   4 , Quan Liao  2 , Xiaoyan Qiu  5 , Benedict Kinny-Köster  1 , Joseph R Habib  1 , Elie M Ghabi  1 , Junke Wang  3 , Eun Ji Shin  6 , Sean X Leng  6 , Syed Z Ali  7 , Elizabeth D Thompson  7 , Jacquelyn W Zimmerman  3 , Christopher R Shubert  1   3 , Kelly J Lafaro  1   3 , Richard A Burkhart  1   3 , William R Burns  1   3 , Lei Zheng  1   3 , Jin He  1   3 , Yupei Zhao  2 , Christopher L Wolfgang  8 , Jun Yu  1   3   6
Affiliations

Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer

Ming Cui et al. Int J Surg. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Conflict of interest statement

All authors approved the manuscript and declared no potential conflicts of interest.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1
Figure 1
Scheme of the study design. FNA, fine needle aspirate; IHC, immunohistochemistry; NAT, neoadjuvant therapy; SIA-IgG, cancer-cell-derived sialylated immunoglobulin G.
Figure 2
Figure 2
Cancer-cell-derived sialylated immunoglobulin G (SIA-IgG) expression in treatment-naïve fine needle aspirate (FNA) specimens and surgically resected primary tumor specimens of pancreatic ductal adenocarcinoma. (A, B) Representative images of negative SIA-IgG expression in FNA specimens. (C, D) Representative images of positive SIA-IgG expression in FNA specimens. (E, F) Representative images of negative SIA-IgG expression in surgically resected specimens. (G, H) Representative images of positive SIA-IgG expression in surgically resected specimens.
Figure 3
Figure 3
The association between SIA-IgG staining in fine needle aspirate specimens and clinicopathological characteristics of 72 patients with pancreatic ductal adenocarcinoma. SIA-IgG, cancer-cell-derived sialylated immunoglobulin G.
Figure 4
Figure 4
Receiver operating characteristic curves based on multivariable regression modeling with and without SIA-IgG showing the role of SIA-IgG expression in fine needle aspirate specimens for predicting pathological response. AUC, area under the ROC curves; SIA-IgG, cancer-cell-derived sialylated immunoglobulin G.
Figure 5
Figure 5
Associations of SIA-IgG expression in pancreatic ductal adenocarcinoma (PDAC) specimens with patient survival. (A, B) Kaplan–Meier curves for overall survival and recurrence-free survival of PDAC patients based on SIA-IgG expression in treatment-naïve fine needle aspirate specimens. (C, D) Kaplan–Meier curves for overall survival and recurrence-free survival of PDAC patients based on SIA-IgG expression in surgically resected primary tumor specimens. SIA-IgG, cancer-cell-derived sialylated immunoglobulin G.
See this image and copyright information in PMC

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