Efficacy analysis of combined detection of 5 Serological Tumor markers including MIF and PIVKA-II for early diagnosis of Primary Hepatic Cancer

Objective: To investigate the efficacy of combined detection of 5 serological tumor markers including macrophage migration inhibitory factor (MIF) and abnormal prothrombin (PIVKA-II) in the early diagnosis of primary liver cancer. Methods: A total of 90 patients with suspected primary liver cancer admitted to our hospital from January 2016 to May 2017 were selected as the research subjects. All patients were examined by imaging and histopathology. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum MIF, GP73 and PIVKA-II. Automatic electrochemiluminescence immunoassay system was used to detect serum AFP and AFP-L3. The diagnostic value of single and combined detection of five serological tumor markers for primary liver cancer was compared and analyzed. Results: Of the 90 suspected patients with primary liver cancer, thirty-seven were excluded and 53 were confirmed. From serum MIF diagnosis, fifty-three patients had positive results for primary liver cancer, of which eight had false positive results, with a sensitivity of 84.91%, a specificity of 78.38%, and an accuracy of 82.22%, respectively. From serum GP73 diagnosis, fifty-six patients had positive results for primary liver cancer, of which 10 had false positive results, with a sensitivity of 86.79%, a specificity of 72.97%, and an accuracy of 81.11%, respectively. From serum PIVKA-II diagnosis, 48 patients had positive results for primary liver cancer, of which seven had false positive results, with the sensitivity of 77.36%, the specificity of 81.08%, and the accuracy of 78.89%, respectively. From serum AFP-L3 diagnosis, fifty-two patients had positive results for primary liver cancer, of which nine had false positive results, with a sensitivity of 81.13%, a specificity of 75.68%, and an accuracy of 78.89% respectively. From serum AFP diagnosis, 57 patients had positive results for primary liver cancer, of which seven had false positive results, with a sensitivity of 83.02%, the specificity of 81.08%, and an accuracy of 82.22%, respectively. From the combined diagnosis of 5 serological tumor markers, fifty-three patients had positive results for primary liver cancer, of which one had a false positive result, with a sensitivity of 98.11%, a specificity of 97.30%, and an accuracy of 97.78%, respectively. Combined diagnosis has significantly higher sensitivity, specificity and accuracy than a single diagnosis (P<0.05). Conclusion: Serum MIF, GP73, PIVKA-II, AFP-L3 and AFP all have certain diagnostic value for primary liver cancer; the combined detection of five serological tumor markers can significantly improve the sensitivity, specificity and accuracy of the diagnosis of primary liver cancer, with higher diagnostic value. doi: https://doi.org/10.12669/pjms.37.5.4264 How to cite this:Huan L. Efficacy analysis of combined detection of 5 Serological Tumor markers including MIF and PIVKA-II for early diagnosis of Primary Hepatic Cancer. Pak J Med Sci. 2021;37(5):---------. doi: https://doi.org/10.12669/pjms.37.5.4264 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comparison of two multiplexed technologies for profiling >1,000 serum proteins that may associate with tumor burden

Background: In this pilot study, we perform a preliminary comparison of two targeted multiplex proteomics technologies for discerning serum protein concentration changes that may correlate to tumor burden in ovarian cancer (OC) patients. Methods: Using the proximity extension assay (PEA) and Quantibody® Kiloplex Array (QKA), we measured >1,000 proteins in the pre-surgical and post-surgical serum from nine OC patients (N=18 samples). We expect that proteins that have decreased significantly in the post-surgical serum concentration may correlate to tumor burden in each patient. Duplicate sera from two healthy individuals were used as controls (N=4 samples). We employed in-house ELISAs to measure five proteins with large serum concentration changes in pre- and post-surgical sera, from four of the original nine patients and the two original controls. Results: Both platforms showed a weak correlation with clinical cancer antigen 125 (CA125) data. The two multiplexed platforms showed a significant correlation with each other for >400 overlapping proteins. PEA uncovered 15 proteins, while QKA revealed 11 proteins, with more than a two-fold post-surgical decrease in at least six of the nine patients. Validation using single enzyme-linked immunosorbent assays (ELISAs) showed at least a two-fold post-surgical decrease in serum concentration of the same patients, as indicated by the two multiplex assays. Conclusion: Both methods identified proteins that had significantly decreased in post-surgical serum concentration, as well as recognizing proteins that had been implicated in OC patients. Our findings from a limited sample size suggest that novel targeted proteomics platforms are promising tools for identifying candidate serological tumor-related proteins. However further studies are essential for the improvement of accuracy and avoidance of false results.

In silico analysis and cluster validation of potential breast cancer nsSNPs of serological tumor marker CA27.29

ABSTRACTBackground & ObjectivesCA27.29 is a breast cancer-associated glycoprotein. Many genetic variations caused by non-synonymous nucleotide polymorphisms (nsSNPs) are known to affect the functionality of the CA27.29 protein.MethodsIn the present manuscript, an in silico analysis of the genetic variations in CA27.29 was done to observe functional nsSNPs that possibly alter its stability. Among 2205 SNPs identified from the publically available SNP database (dbSNP), 213 (9.66%) synonymous SNPs, 24 (1.09%) non-synonymous SNPs, and 1351 (61.27%) noncoding intronic SNPs were observed. The function predictability tools SIFT, Provean and Polyphen2 were used to uncover variations in the analyzed nsSNPs and their functionality.ResultsA total of 16, 20 and 10 non-synonymous SNPs (nsSNPs) were predicted to be damaging or deleterious by SIFT, Polyphen, and Provean tools respectively. Intriguingly, 9 nsSNPs were predicted to be damaging by all the three tools used while 4 nsSNPs were predicted to be damaging by SIFT and Polyphen tools. The substitutions C/G->T and G->A/T were observed to be dominant in the analyzed nsSNPs that probably have damaging role to CA27.29 glycoprotein. Moreover, the validation of results using ClinVar tool revealed that all the analyzed possibly, probably and highly damaging nsSNPs are yet to be reported and studied. Besides this, we found Global minor allele frequency (Global MAF) for only 11 nsSNPs, the values of which were observed to be <0.1% that further confirmed the novelty of the analyzed variants.Interpretation & ConclusionsAmong the analyzed nsSNPs, 3 nsSNPs rs145691584, rs148332231 and rs191544901 were found to be located in 3’UTR region of CA27.29 gene that were assumed to have the possible functional roles in altering the protein stability. The present study is useful to gain useful insights into the genetic variations in nsSNPs that may playing a critical role in determining the susceptibility to breast cancer.

KIM-1 as a potential serological/urinological tumor-associated marker of renal cell carcinoma and chemotherapy nephrotoxicity

The last decades are characterized by an active search for highly sensitive and specific urinological and serological tumor-associated markers of renal cell carcinoma. This review analyses the results of studies of traditional serological tumor-associated markers and a potential new tumor-associated marker of renal cell carcinoma: kidney injury molecule-1, or KIM-1. The structure, sources and functions of KIM-1 in normal conditions and in damaged renal tubules, its potential role in carcinogenesis are described. The experience of using KIM-1 for specifying diagnosis of the most common histological types of renal cell carcinoma is analyzed. Data on KIM-1 expression in malignant tumors in other locations and non-oncological kidney disorders are presented. The role of KIM-1 in early diagnosis of nephrotoxic effect of antitumor drugs is described. The accumulated data is promising in regards to using KIM-1 in clinical oncology as a urinological and serological marker of renal cell carcinoma and chemotherapy nephrotoxicity.