Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma

Hu, Dingyuan; Ansari, Daniel; Pawłowski, Krzysztof; Zhou, Qimin; Sasor, Agata; Welinder, Charlotte; Kristl, Theresa; Bauden, Monika; Rezeli, Melinda; Jiang, Yi; Markó-Varga, György; Andersson, Roland

doi:10.18632/oncotarget.23929

Cited by 42 publications

(34 citation statements)

References 93 publications

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“…2). It is noted that the relationship between expression level of CLIC3 and prognosis were opposite to the previous reports [13][14][15][16][17], although the types of cancer are different. In fact, expression level of CLIC3 was negatively correlated with pathological tumor depth (Table 1).…”

Section: No Effects Of Clic3 Overexpression On Migration and Invasioncontrasting

confidence: 78%

“…On the other hand, it has been reported that chloride intracellular channel 3 (CLIC3) plays roles as not only a soluble protein, but also an organellar membrane protein [10][11][12]. Moreover, CLIC3 is associated with poor prognosis in pancreatic cancer, breast cancer, ovarian cancer, and malignant pleural mesothelioma [13][14][15][16][17]. Taken together, we have raised two questions: (1) Does CLIC3 act as a Cl − channel in the membrane?, and (2) Page 2 of 11 Kawai et al J Physiol Sci (2020) 70:15 Is CLIC3 expression associated with prognosis of gastric cancer?.…”

Section: Introductionmentioning

confidence: 99%

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Pathophysiological properties of CLIC3 chloride channel in human gastric cancer cells

et al. 2020

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Pathophysiological functions of chloride intracellular channel protein 3 (CLIC3) in human gastric cancer have been unclear. In the tissue microarray analysis using 107 gastric cancer specimens, CLIC3 expression was negatively correlated with pathological tumor depth, and the patients with lower expression of CLIC3 exhibited poorer prognosis. CLIC3 was expressed in the plasma membrane of cancer cells in the tissue. CLIC3 expression was also found in a human gastric cancer cell line (MKN7). In whole-cell patch-clamp recordings of the cells expressing CLIC3, NPPB-sensitive outwardly rectifying Cl − currents were observed. Cell proliferation was significantly accelerated by knockdown of CLIC3 in MKN7 cells. On the other hand, the proliferation was attenuated by exogenous CLIC3 expression in human gastric cancer cells in which endogenous CLIC3 expression is negligible. Our results suggest that CLIC3 functions as a Cl − channel in the plasma membrane of gastric cancer cells and that decreased expression of CLIC3 results in unfavorable prognosis of gastric cancer patients.

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Section: No Effects Of Clic3 Overexpression On Migration and Invasioncontrasting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Pathophysiological properties of CLIC3 chloride channel in human gastric cancer cells

et al. 2020

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“…In a previous mass spectrometry-based study, we identified galectin 4 as a down-regulated protein in short-term survivors of pancreatic cancer [10]. The present study aimed to elucidate the prognostic role of galectin 4 in a large cohort of patients with resectable pancreatic cancer.…”

Section: Introductionmentioning

confidence: 88%

Galectin 4 is a biomarker for early recurrence and death after surgical resection for pancreatic ductal adenocarcinoma

Ansari

Zhou

et al. 2019

Scandinavian Journal of Gastroenterology

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Background: Galectins are a group of carbohydrate-binding proteins that are involved in neoplastic development and progression. In a previous mass spectrometry-based study, we identified galectin 4 as a down-regulated protein in short-term survivors of pancreatic cancer. This study was performed to validate the prognostic value of galectin 4 in a larger cohort of pancreatic cancer patients undergoing surgical resection. Methods: Galectin 4 expression was evaluated by tissue microarrays and immunohistochemistry in 140 patients with surgically resected pancreatic cancer. Kaplan-Meier and Cox proportional hazards modeling were used to explore the association between galectin 4 and survival. Results: Galectin 4 staining expression was positive in 111 cases (79.3%). The expression of galectin 4 was significantly associated with tumor size (p ¼ .008) and differentiation (p ¼ .001). Galectin 4 expression was significantly correlated with disease recurrence within 1 year of surgery (adjusted HR 0.485, p ¼ .027). There was also a significant association between galectin 4 and overall survival at 1 year (adjusted HR 0.482, p ¼ .047) and at 3 years (adjusted HR 0.550, p ¼ .025). Conclusion: Galectin 4 expression is a novel biomarker for early recurrence and mortality after surgical resection for pancreatic cancer.

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“…Protein expression patterns in PDAC liver metastases also have the potential to reveal new associations with clinical outcomes or identify novel therapeutic targets (14,31). With the understanding that PDAC is not a singular disease, we hypothesized that associations between protein expression and patient survival might display subtype-specific characteristics.…”

Section: Association Between Individual Protein Expression and Survivmentioning

confidence: 99%

The Proteomic Landscape of Pancreatic Ductal Adenocarcinoma Liver Metastases Identifies Molecular Subtypes and Associations with Clinical Response

Law

Lagundžin

Clement

et al. 2020

Clinical Cancer Research

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Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease that can be separated into distinct subtypes based on molecular signatures. Identifying PDAC subtype-specific therapeutic vulnerabilities is necessary to develop precision medicine approaches to treat PDAC. Experimental Design: A total of 56 PDAC liver metastases were obtained from the UNMC Rapid Autopsy Program and analyzed with quantitative proteomics. PDAC subtypes were identified by principal component analysis based on protein expression profiling. Proteomic subtypes were further characterized by the associated clinical information, including but not limited to survival analysis, drug treatment response, and smoking and drinking status. Results: Over 3,960 proteins were identified and used to delineate four distinct PDAC microenvironment subtypes: (i) metabolic; (ii) progenitor-like; (iii) proliferative; and (iv) inflammatory. PDAC risk factors of alcohol and tobacco consumption correlate with subtype classifications. Enhanced survival is observed in FOLFIRINOX treated metabolic and progenitor-like subtypes compared with the proliferative and inflammatory subtypes. In addition, TYMP, PDCD6IP, ERAP1, and STMN showed significant association with patient survival in a subtype-specific manner. Gemcitabine-induced alterations in the proteome identify proteins, such as serine hydroxymethyltransferase 1, associated with drug resistance. Conclusions: These data demonstrate that proteomic analysis of clinical PDAC liver metastases can identify molecular signatures unique to disease subtypes and point to opportunities for therapeutic development to improve the treatment of PDAC.

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Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma

Cited by 42 publications

References 93 publications

Pathophysiological properties of CLIC3 chloride channel in human gastric cancer cells

Pathophysiological properties of CLIC3 chloride channel in human gastric cancer cells

Galectin 4 is a biomarker for early recurrence and death after surgical resection for pancreatic ductal adenocarcinoma

The Proteomic Landscape of Pancreatic Ductal Adenocarcinoma Liver Metastases Identifies Molecular Subtypes and Associations with Clinical Response

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