Immune-Complexome Analysis Identifies Immunoglobulin-Bound Biomarkers That Predict the Response to Chemotherapy of Pancreatic Cancer Patients

Pancreatic Ductal Adenocarcinoma (PDA) is an aggressive malignancy with a very poor outcome. Although chemotherapy (CT) treatment has poor efficacy, it can enhance tumor immunogenicity. Tumor-Associated Antigens (TAA) are self-proteins that are overexpressed in tumors that may induce antibody production and can be PDA theranostic targets. However, the prognostic value of TAA-antibody association as Circulating Immune Complexes (CIC) has not yet been elucidated, mainly due to the lack of techniques that lead to their identification. In this study, we show a novel method to separate IgG, IgM, and IgA CIC from sera to use them as prognostic biomarkers of CT response. The PDA Immune-Complexome (IC) was identified using a LTQ-Orbitrap mass spectrometer followed by computational analysis. The analysis of the IC of 37 PDA patients before and after CT revealed differential associated antigens (DAA) for each immunoglobulin class. Our method identified different PDA-specific CIC in patients that were associated with poor prognosis patients. Finally, CIC levels were significantly modified by CT suggesting that they can be used as effective prognostic biomarkers to follow CT response in PDA patients.

Download Full-text

Mitochondrial DNA and MitomiR Variations in Pancreatic Cancer: Potential Diagnostic and Prognostic Biomarkers

International Journal of Molecular Sciences ◽

10.3390/ijms22189692 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9692

Author(s):

Loredana Moro

Keyword(s):

Pancreatic Cancer ◽

Current Knowledge ◽

Locally Advanced ◽

Prognostic Biomarkers ◽

Mitochondrial Proteins ◽

Ductal Adenocarcinoma ◽

Metastatic Progression ◽

Response To Chemotherapy ◽

Personalized Cancer Therapy ◽

Personalized Cancer

Pancreatic cancer is an aggressive disease with poor prognosis. Only about 15–20% of patients diagnosed with pancreatic cancer can undergo surgical resection, while the remaining 80% are diagnosed with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). In these cases, chemotherapy and radiotherapy only confer marginal survival benefit. Recent progress has been made in understanding the pathobiology of pancreatic cancer, with a particular effort in discovering new diagnostic and prognostic biomarkers, novel therapeutic targets, and biomarkers that can predict response to chemo- and/or radiotherapy. Mitochondria have become a focus in pancreatic cancer research due to their roles as powerhouses of the cell, important subcellular biosynthetic factories, and crucial determinants of cell survival and response to chemotherapy. Changes in the mitochondrial genome (mtDNA) have been implicated in chemoresistance and metastatic progression in some cancer types. There is also growing evidence that changes in microRNAs that regulate the expression of mtDNA-encoded mitochondrial proteins (mitomiRs) or nuclear-encoded mitochondrial proteins (mitochondria-related miRs) could serve as diagnostic and prognostic cancer biomarkers. This review discusses the current knowledge on the clinical significance of changes of mtDNA, mitomiRs, and mitochondria-related miRs in pancreatic cancer and their potential role as predictors of cancer risk, as diagnostic and prognostic biomarkers, and as molecular targets for personalized cancer therapy.

Download Full-text

Immune-Related Circulating miR-125b-5p and miR-99a-5p Reveal a High Recurrence Risk Group of Pancreatic Cancer Patients after Tumor Resection

Applied Sciences ◽

10.3390/app9224784 ◽

2019 ◽

Vol 9 (22) ◽

pp. 4784

Author(s):

Vietsch ◽

Peran ◽

Suker ◽

van den Bosch ◽

Sijde ◽

...

Keyword(s):

Cancer Progression ◽

B Lymphocyte ◽

Immune Cell ◽

Tumor Resection ◽

Progression Free Survival ◽

Tumor Stroma ◽

Recurrence Risk ◽

High Serum ◽

Ductal Adenocarcinoma ◽

Before And After

Clinical follow-up aided by changes in the expression of circulating microRNAs (miRs) may improve prognostication of pancreatic ductal adenocarcinoma (PDAC) patients. Changes in 179 circulating miRs due to cancer progression in the transgenic KrasG12D/+; Trp53R172H/+; P48-Cre (KPC) animal model of PDAC were analyzed for serum miRs that are altered in metastatic disease. In addition, expression levels of 250 miRs were profiled before and after pancreaticoduodenectomy in the serum of two patients with resectable PDAC with different progression free survival (PFS) and analyzed for changes indicative of PDAC recurrence after resection. Three miRs that were upregulated ≥3-fold in progressive PDAC in both mice and patients were selected for validation in 26 additional PDAC patients before and after resection. We found that high serum miR-125b-5p and miR-99a-5p levels after resection are significantly associated with shorter PFS (HR 1.34 and HR 1.73 respectively). In situ hybridization for miR detection in the paired resected human PDAC tissues showed that miR-125b-5p and miR-99a-5p are highly expressed in inflammatory cells in the tumor stroma, located in clusters of CD79A expressing cells of the B-lymphocyte lineage. In conclusion, we found that circulating miR-125b-5p and miR-99a-5p are potential immune-cell related prognostic biomarkers in PDAC patients after surgery.

Download Full-text

Computational analysis identifies putative prognostic biomarkers of pathological scarring in skin wounds

Journal of Translational Medicine ◽

10.1186/s12967-018-1406-x ◽

2018 ◽

Vol 16 (1) ◽

Cited By ~ 4

Author(s):

Sridevi Nagaraja ◽

Lin Chen ◽

Luisa A. DiPietro ◽

Jaques Reifman ◽

Alexander Y. Mitrophanov

Keyword(s):

Computational Analysis ◽

Prognostic Biomarkers ◽

Skin Wounds

Download Full-text

Application of a Liquid Chromatography Tandem Mass Spectrometry Method for the Simultaneous Detection of Seven Allergenic Foods in Flour and Bread and Comparison of the Method with Commercially Available ELISA Test Kits

Journal of AOAC International ◽

10.1093/jaoac/94.4.1060 ◽

2011 ◽

Vol 94 (4) ◽

pp. 1060-1068 ◽

Cited By ~ 51

Author(s):

Julia Heick ◽

Markus Fischer ◽

Sandra Kerbach ◽

Ulrike Tamm ◽

Bert Popping

Keyword(s):

Simultaneous Detection ◽

Elisa Test ◽

Spectrometry Method ◽

Chromatography Tandem Mass Spectrometry ◽

Model Matrix ◽

Before And After ◽

Liquid Chromatography Tandem Mass ◽

Novel Method ◽

Detection Capabilities ◽

Baked Products

Abstract To protect the allergic consumer, analytical methods need to be capable of detecting allergens in fnished products that typically contain multiple allergens. An LC/MS/MS method for simultaneous detection of seven allergens was developed and compared with commercially available ELISA kits. The detection capabilities of this novel method were demonstrated by analyzing incurred material containing milk, egg, soy, peanut, hazelnut, walnut, and almond. Bread was chosen as a model matrix. To assess the inﬂuence of baking on the method’s performance, analysis was done before and after baking. The same samples were analyzed with ELISA test kits from ELISA Systems, Morinaga, Neogen, and r-Biopharm. Peanut, hazelnut, walnut, and almond could be detected with both ELISA and LC/MS/MS regardless of whether the product was baked or not. LC/MS/MS clearly showed superior detection of milk in processed matrixes compared to ELISA, which exhibited signifcantly lower sensitivities when analyzing the baked products. Similar results were obtained when analyzing egg; however, one kit was capable of detecting egg in the processed samples as well.

Download Full-text

The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

Galen Medical Journal ◽

10.31661/gmj.v10i0.2288 ◽

2021 ◽

Vol 10 ◽

pp. e2288

Author(s):

Mahdiyar Iravani Saadi ◽

Mani Ramzi ◽

Aliasghar Karimi ◽

Maryam Owjfard ◽

Mahmoud Torkamani ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Chemotherapy ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Hematologic Malignancy ◽

Quantitative Polymerase Chain Reaction ◽

Remission Induction ◽

Response To Chemotherapy ◽

Before And After ◽

Acute Myeloid

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

Download Full-text

Protein kinase-coding genes as novel diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma

The Annals of Clinical and Analytical Medicine ◽

10.4328/acam.20351 ◽

2020 ◽

Vol 11 (6) ◽

Keyword(s):

Protein Kinase ◽

Pancreatic Ductal Adenocarcinoma ◽

Prognostic Biomarkers ◽

Ductal Adenocarcinoma

Download Full-text

Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis

Journal of Oncology ◽

10.1155/2021/6646459 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Jianye Tan ◽

Haofeng Liang ◽

Bingsheng Yang ◽

Shuang Zhu ◽

Guofeng Wu ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Survival Rates ◽

Prognostic Biomarkers ◽

Messenger Rnas ◽

Hub Genes ◽

Cox Regression Analysis ◽

Expression Levels ◽

Kaplan Meier ◽

Before And After

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

Download Full-text