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Cancers
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Plasma Proteins and Cancer
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Plasma Proteins and Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 20377

Special Issue Editor

Dr. Stefan Enroth

E-Mail Website
Guest Editor
Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden
Interests: Biomarkers; Normal variation; Prediction; Proteomics; Genomics

Special Issue Information

Dear Colleagues,

Human plasma contains a large number of proteins and comes in contact with virtually all cells in the human body. This creates opportunities for detecting or monitoring cancer in any location in the body in an easily accessible sample. Circulating protein biomarkers are today used for general detection and triaging of for instance prostate cancer (PSA) and ovarian cancer (CA125/Mucin16). Technological developments now allow for high-throughput proteomics and recent years have seen a large variety of proposed protein biomarkers used alone or in combination for screening, diagnosis and treatment monitoring of cancers.

Many of these techniques for protein quantification also work from dried samples. Exciting times lie ahead with possible applications in screening programmes for early cancer detection or disease management implemented as home-sampling of dried whole blood for plasma protein characterization.

There are however many challenges to address; large differences in plasma protein concentrations complicates measurement and can affect using combinations of biomarkers, personalized variation in the plasma proteome from genetics, anthropometrics and lifestyle choices could also impact the precision of prediction models. 

In this Special Issue, we will publish reviews and original research that push the current boundaries of plasma proteins and cancer. This include studies on technical feasibility, basic biology and clinical application of screening, diagnosis and prognostics of cancers. We especially welcome studies on alternative collecting formats for plasma-based analyses. 

Dr. Stefan Enroth
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Editorial

Jump to: Research, Review

2 pages, 153 KiB  
Editorial
Plasma Proteins and Cancer
by Stefan Enroth
Cancers 2021, 13(5), 1062; https://doi.org/10.3390/cancers13051062 - 03 Mar 2021
Cited by 5 | Viewed by 1349
Abstract
The human plasma comes into contact with virtually all the cells in the human body and can be easily sampled through phlebotomy [...] Full article
(This article belongs to the Special Issue Plasma Proteins and Cancer)

Research

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17 pages, 1040 KiB  
Article
Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer
by Christi M. J. Steendam, G. D. Marijn Veerman, Melinda A. Pruis, Peggy Atmodimedjo, Marthe S. Paats, Cor van der Leest, Jan H. von der Thüsen, David C. Y. Yick, Esther Oomen-de Hoop, Stijn L. W. Koolen, Winand N. M. Dinjens, Ron H. N. van Schaik, Ron H. J. Mathijssen, Joachim G. J. V. Aerts, Hendrikus Jan Dubbink and Anne-Marie C. Dingemans
Cancers 2020, 12(11), 3179; https://doi.org/10.3390/cancers12113179 - 29 Oct 2020
Cited by 12 | Viewed by 2569
Abstract
Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC), not all patients benefit. We therefore explored the impact of the presence of mutations found in cell-free DNA (cfDNA) and [...] Read more.
Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC), not all patients benefit. We therefore explored the impact of the presence of mutations found in cell-free DNA (cfDNA) and TKI plasma concentrations during treatment on progression-free survival (PFS). In the prospective START-TKI study blood samples from 41 patients with EGFR-mutated NSCLC treated with EGFR-TKIs were available. Next generation sequencing (NGS) on cfDNA was performed, and plasma TKI concentrations were measured. Patients without complete plasma conversion of EGFR mutation at week 6 had a significantly shorter PFS (5.5 vs. 17.0 months, p = 0.002) and OS (14.0 vs. 25.5 months, p = 0.003) compared to patients with plasma conversion. In thirteen (second line) osimertinib-treated patients with a (plasma or tissue) concomitant TP53 mutation at baseline, PFS was significantly shorter compared to six wild-type cases; 8.8 vs. 18.8 months, p = 0.017. Erlotinib Cmean decrease of ≥10% in the second tertile of treatment was also associated with a significantly shorter PFS; 8.9 vs. 23.6 months, p = 0.037. We obtained evidence that absence of plasma loss of the primary EGFR mutation, isolated plasma p.T790M loss after six weeks, baseline concomitant TP53 mutations, and erlotinib Cmean decrease during treatment are probably related to worse outcome. Full article
(This article belongs to the Special Issue Plasma Proteins and Cancer)
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20 pages, 2221 KiB  
Article
Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer
by Sharad Purohit, Wenbo Zhi, Daron G. Ferris, Manual Alverez, Lynn Kim Hoang Tran, Paul Minh Huy Tran, Boying Dun, Diane Hopkins, Bruno dos Santos, Sharad Ghamande and Jin-Xiong She
Cancers 2020, 12(10), 2899; https://doi.org/10.3390/cancers12102899 - 09 Oct 2020
Cited by 11 | Viewed by 2950
Abstract
Molecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an [...] Read more.
Molecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an impact on disease specific survival (DSS) (Hazzard’s ratio; HR = 1.51–2.1). Surprisingly, all ten proteins are implicated in senescence-associated secreted phenotype (SASP), a hallmark of cellular senescence. Machine learning using Ridge regression of these SASP proteins can robustly stratify patients with high SASP, which is associated with poor survival, and patients with low SASP associated with good survival (HR = 3.09–4.52). Furthermore, brachytherapy, an effective therapy for cervical cancer, greatly improves survival in SASP-high patients (HR = 3.3, p < 5 × 10−5) but has little impact on survival of SASP-low patients (HR = 1.5, p = 0.31). These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer. Full article
(This article belongs to the Special Issue Plasma Proteins and Cancer)
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13 pages, 1266 KiB  
Article
Preoperative Fasting and General Anaesthesia Alter the Plasma Proteome
by Ulf Gyllensten, Sofia Bosdotter Enroth, Karin Stålberg, Karin Sundfeldt and Stefan Enroth
Cancers 2020, 12(9), 2439; https://doi.org/10.3390/cancers12092439 - 27 Aug 2020
Cited by 5 | Viewed by 3045
Abstract
Background: Blood plasma collected at time of surgery is an excellent source of patient material for investigations into disease aetiology and for the discovery of novel biomarkers. Previous studies on limited sets of proteins and patients have indicated that pre-operative fasting and anaesthesia [...] Read more.
Background: Blood plasma collected at time of surgery is an excellent source of patient material for investigations into disease aetiology and for the discovery of novel biomarkers. Previous studies on limited sets of proteins and patients have indicated that pre-operative fasting and anaesthesia can affect protein levels, but this has not been investigated on a larger scale. These effects could produce erroneous results in case-control studies if samples are not carefully matched. Methods: The proximity extension assay (PEA) was used to characterize 983 unique proteins in a total of 327 patients diagnosed with ovarian cancer and 50 age-matched healthy women. The samples were collected either at time of initial diagnosis or before surgery under general anaesthesia. Results: 421 of the investigated proteins (42.8%) showed statistically significant differences in plasma abundance levels comparing samples collected at time of diagnosis or just before surgery under anaesthesia. Conclusions: The abundance levels of the plasma proteome in samples collected before incision, i.e., after short-time fasting and under general anaesthesia differs greatly from levels in samples from awake patients. This emphasizes the need for careful matching of the pre-analytical conditions of samples collected from controls to cases at time of surgery in the discovery as well as clinical use of protein biomarkers. Full article
(This article belongs to the Special Issue Plasma Proteins and Cancer)
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18 pages, 1894 KiB  
Article
Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer
by Kimi Drobin, Michal Marczyk, Martin Halle, Daniel Danielsson, Anna Papiez, Traimate Sangsuwan, Annika Bendes, Mun-Gwan Hong, Ulrika Qundos, Mats Harms-Ringdahl, Peter Wersäll, Joanna Polanska, Jochen M. Schwenk and Siamak Haghdoost
Cancers 2020, 12(3), 753; https://doi.org/10.3390/cancers12030753 - 22 Mar 2020
Cited by 20 | Viewed by 5595
Abstract
Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear [...] Read more.
Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depend on the patient’s radiosensitivity. Currently, there is no assay available that can reliably predict the individual’s response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls.. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual’s risk of experiencing radiation-induced toxicity. Full article
(This article belongs to the Special Issue Plasma Proteins and Cancer)
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Review

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15 pages, 1074 KiB  
Review
Plasma Androgen Receptor in Prostate Cancer
by Vincenza Conteduca, Giorgia Gurioli, Nicole Brighi, Cristian Lolli, Giuseppe Schepisi, Chiara Casadei, Salvatore Luca Burgio, Stefania Gargiulo, Giorgia Ravaglia, Lorena Rossi, Amelia Altavilla, Alberto Farolfi, Cecilia Menna, Sarah Pia Colangione, Mario Pulvirenti, Antonino Romeo and Ugo De Giorgi
Cancers 2019, 11(11), 1719; https://doi.org/10.3390/cancers11111719 - 04 Nov 2019
Cited by 14 | Viewed by 4008
Abstract
The therapeutic landscape of prostate cancer has expanded rapidly over the past 10 years, and there is now an even greater need to understand the biological mechanisms of resistance and to develop noninvasive biomarkers to guide treatment. The androgen receptor (AR) is known [...] Read more.
The therapeutic landscape of prostate cancer has expanded rapidly over the past 10 years, and there is now an even greater need to understand the biological mechanisms of resistance and to develop noninvasive biomarkers to guide treatment. The androgen receptor (AR) is known to be involved in the pathogenesis and progression of prostate cancer. Recently, highly sensitive next-generation sequencing and PCR-based methods for analyzing androgen receptor gene (AR) copy numbers (CN) and mutations in plasma were established in cell-free DNA (cfDNA) of patients with castration-resistant prostate cancer (CRPC) treated with different drugs. The study of cfDNA holds great promise for improving treatment in CRPC, especially in the advanced stage of the disease. Recent findings showed the significant association of plasma AR aberrations with clinical outcome in CRPC patients treated with AR-directed therapies, whereas no association was observed in patients treated with taxanes. This suggests the potential for using plasma AR as a biomarker for selecting treatment, i.e., hormone therapy or chemotherapy, and the possibility of modulating taxane dose. In recent years, plasma AR status has also been investigated in association with novel agents, such as 177Lu-PSMA radioligand therapy and PARP inhibitors. This review will focus on AR testing in plasma that may have clinical utility for treatment selection in advanced prostate cancer. Full article
(This article belongs to the Special Issue Plasma Proteins and Cancer)
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