Deputy Editor Guy Orchard outlines the content in the latest issue, which includes a variety of subjects and a wide range of discipline-specific papers.
The study of cirrhosis and hepatocellular carcinoma (HCC) of the liver figure significantly in this issue. We start with Rowida et al.’s publication on the significance of a single nucleotide polymorphism (SNP) APa1 in the vitamin D receptor in HCC, arising from chronic hepatitis C virus (HCV) infection in liver cirrhosis. Employing a PCR-RFLP technique, the Apa1 CC genotype was found more frequently (75%) in HCC than in cirrhosis (35%) compared with standard controls. Providing evidence that Apa1 CC genotype is linked with HCC in HCV cirrhotic patients and could be used as a biomarker predictor for HCC occurrence in HCV cirrhosis.
Poor prognosis of HCC is often related to the late detection of the disease in its advanced stage. Here Attallah et al. hypothesise that collagen III and matrix metalloproteinase-1 (MMP-1) and their respective ratios are effective markers for early identification of HCC when used alongside serum alpha-fetoprotein (AFP), alkaline phosphatase and bilirubin. Here the authors assess 148 patients with HCC using imaging ultrasound and computed tomography and employ western blotting techniques on sera using ELISA. In HCC patients, collagen III and MMP-1 levels were higher than in fibrotic and cirrhotic control patient groups. Conversely HCC patients showed a lower concentration of MMP-1 than the control group. Liver function tests were abnormal; scores for AFP, alkaline phosphatase and bilirubin together with collagen III / MMP-1 ratio (CMR), termed the ABC test, were constructed and found to be statistically significant. As a result the authors conclude that the HCC-ABC test provided a promising index with a high degree of accuracy for HCC early detection and diagnosis.
Cancer stem cell markers
Next we take a look at the synergistic effects of CD44, a cancer stem cell marker, and the embryonic stem cell transcription factor Nanog on bladder cancer prognosis. The authors (Siddiqui et al.) take a look at the detection of CD44 in the basal layer of urothelial carcinoma and Nanog in bladder cancer employing immunohistochemistry on 112 bladder cancer cases. It was found that there was a significant correlation between the two markers in that bladder patients with a high CD44 and Nanog expression had poor recurrence-free survival and poor overall survival. A combined index of CD44 and Nanog expression was felt to be a prognostic predictor of recurrence-free survival and overall survival in bladder cancer.
Gastric cancer
Following on from this we read the paper by Raad et al. on the association of rs2620381 polymorphism in miR-627 in gastric cancer. miRNAs are small endogenous non-coding RNAs with a length of 18-25 ribonucleotides that play important roles in cancer-related biological mechanisms, including cellular proliferation, apoptosis, angiogenesis, migration and invasion. A total of 280 healthy control patients were assessed in conjunction with 240 gastric cancer patients. Using genotyping by allele, specific PCR in conjunction with in silico analyses were carried out. Any C genotypes in rs2620381 were found to be linked to gastric cancer. There were no links between age, sex, tumour type, distant metastasis and tumour stages and miR-627 polymorphism in gastric cancer patients, thus providing evidence that the presence of the C single nucleotide polymorphism (SNP) in mIR-627 rs2620381 is linked with gastric cancer.
Cervical cancer
Kushwah et al. report on the study of cytokine gene variants and treatment outcomes of cicplatin-based concomitant chemoradiotherapy in cervical cancer. Cervical cancer remains the most common cancer among women world-wide after breast cancer. Standard treatment for cervical cancer is cisplatin-based concomitant chemoradiotherapy. By studying cytokine (IL-1, IL-6 and TNF gene) expression within the chronic inflammation in uterine cervix they found that SNPs in IL-1RN, IL-1b, IL-6 and TNFa were linked with cervical cancer. It was postulated that certain cytokine gene variants may help detect susceptibility to cervical cancer and further predict responses to chemoradiotherapy.
Chronic bacterial inflammation
A case study by Mohaghegh et al. on xanthogranulomatous pyelonephritis (XGP) masquerading as cystic renal cell carcinoma highlights a challenging case of XGP – a rare chronic bacterial inflammation of the renal parenchyma. Originally reported as a case of renal cell carcinoma, this case study highlights the diagnostic pitfalls of managing patients with XGP and explains why partial nephrectomy may be appropriate in the management of selective XGP patients.
Hepatitis C
Again we look at the value of SNP, this time as a Biomedical Science in Brief paper on rs12979860 and rs8099917 in IL-28B, and spontaneous clearance of hepatitis C genotype 4. Hepatitis C virus (HCV) is associated with liver disease worldwide with an estimated 170 million infected cases. A study by Mansoura University, Egypt compared 100 patients with HCV antibodies two or more times with positive HCV-RNA by real-time PCR two or more times over six months and elevated alanine aminotransferases (ALT), with 100 patients positive for HCV-IgG at two or more times and negative HCV-RNA by real time PCR within six months and with normal ALT. Evaluation of liver function tests and employing DNA extraction and amplification of rs8099917 and rs12979860, it was found that there was a marked differences in genotypes and alleles in both rs12979860 and rs8099917 in the two groups – those with TT genotype and T allele in rs12979860 were more likely to have chronic hepatitis C, while those with the TT genotype and T allele in rs8099917 were more likely to have spontaneously cleared the virus. It was concluded that an early stage of therapy in patients with an unfavourable IL28B genotype would be beneficial.
Hepatocellular carcinoma
Continuing in the Biomedical Science in Brief theme of studies on hepatocellular carcinoma, Elbaz et al. investigated the role of malondialdehyde (MDA) and C-reactive protein (CRP) as prognostic markers of hepatocellular carcinoma. A total of 180 patients with HCC and chronic HCV infection were compared with 180 age- and sex-matched cirrhotic chronic HCV patients free of HCC. In this group, serum levels of CRP and MDA were studied. MDA is a low molecular weight aldehyde produced by the attack of free radicals to polyunsaturated fatty acids during cellular membrane phospholipid degradation. A significant increase in serum CRP, MDA, bilirubin, AFP and AST levels were found in HCC patients. CRP and MDA were found to be the strongest differentiators of the two groups. The study revealed that serum levels of MDA were higher in patients with HCC versus the control cirrhotic group. In addition, MDA was higher in HCC patients with tumour sizes >5cm. The same pattern was found for levels of serum CRP, suggesting that CRP is also an indicator of poor prognosis among patients with HCC.
Carbapenemase-producing Enterobacterales
The second edition finishes with a third Biomedical Science in Brief paper, by Cafferkey et al., on improving the processing time for the detection of carbapenemase-producing Enterobacterales (CPE) using an evolving algorithm. Recognising CPE is challenging in a routine diagnostic laboratory. Here, the authors present an interesting immunochromatographic-based algorithm assay to confirm CPE production with a modified carbapenem inactivation method test validating negative tests. This approach also demonstrated reduced processing times by demonstrating increasing numbers of isolates.
CPD
One of these articles may be the subject of a Journal-based learning exercise for those seeking to improve their continuing professional development profile.