Middle East Journal of Cancer
Volume:12 Issue: 1, Jan 2021

We aimed to determine the role of receptor tyrosine kinases (RTK) signaling family genes in the development of oral squamous cell carcinoma (OSCC). In the present in silico study, 40 whole genome sequences of patients with OSCC from the cBioPortal was analysed to identify the mutations in the genes of the RTK signaling pathway. Using the STRING v10.5, we further checked the gene with the highest frequency of mutations for its protein interactions. The obtained protein interaction network was used to identify the possible pathways related to disease phenotype. Epidermal growth factor receptor (EGFR) gene showed the highest frequency of mutation (5%) among the 16 genes clustered in the RTK signaling pathway as available in the cBioportal database. Missense mutations viz., G203E, R521K were identified in the EGFR gene. The other genes which returned positive results during analysis were ERBB4 (D245N, L993S), PDGFB (R100H), and PDGFRB (L667M). The in silico method of analysis can be a contemporary approach for identifying possible mutations or pathways associated with the development of OSCC. Further high throughput strategies should be applied to substantiate the role of the genes identified in the present study and draw conclusive evidence as to their association with the disease phenotype.

Recent studies have reported that melanoma antigen (MAGE) gene is expressed in a variety of cancers and testicular tissues. The expression of MAGE-A genes could be used for biomarkers with high tumor specificity; however, there is still a lack of data on most solid tumors. The objective of this study was to construct novel universal primers for detecting the mRNA of MAGE A1-10 genes in lung cancer patients.
We conducted this cross-sectional study in 2017 at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. The specimens were a testicular tissue and 15 core biopsies of lung cancer tissues. We designed the universal primers to bind the mRNA of MAGE A1, A2, A2B, A3, A4, A5, A6, A8, A9, A9B, and A10 regions; the assay was performed by nested PCR and continued by direct sequencing.
Using the universal primer MAGE A1-10, the PCR was able to detect the MAGE A mRNA of 10 subtypes of MAGE A from testicular and lung cancer tissues. The sequences analysis of individual MAGE A1-10 showed the same homology with MAGE A from GenBank data. Among the 15 lung cancer patients, 13/15 (86.67%) tested positive for GAPDH; subsequently, they were considered for MAGE-A gene detection; while, those testing negative for GAPDH were excluded. The PCR results showed that 12/13 (92.31%) had positive MAGE A1-10 tests and 3/13 (23.08%) tested positive for MAGE A1-6.
This finding showed that the novel universal primers could be applied as a new tool for detecting MAGE A1-10 expression in cancer cells.

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer. In some studies, parvovirus B19 (PVB19) infection was involved in the pathogenesis of thyroid diseases such as Graves’ disease, Hashimoto thyroiditis, and thyroid cancer. PVB19 induces chronic inflammation in thyroid, which can lead to carcinogenesis through the effect of inflammatory mediators. The association of PVB19 with PTC tumorigenesis is still a matter of controversy. We evaluated the correlation of PVB19 with PTC and, for the first time, pathologic features.
This cross-sectional retrospective study focused on the thyroid specimens of 82 patients with PTC and 77 patients with benign thyroid nodules. We conducted the present study from March 2014 to November 2017 in the hospitals affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. We evaluated the presence of PVB19 DNA by nested polymerase chain reaction method in PTC, adjacent non-malignant tissues, and benign thyroid nodules. PVB19 positivity was also compared between PTC and two other groups. We further investigated the association of pathologic features and tumor staging with PVB19 positivity.
Of the patients, 81% were female. We detected PVB19 positivity in 9.8% of PTC specimens and 0.01 of adjacent non-malignant tissues (P=0.016). None of the benign thyroid nodule specimens had PVB19 DNA, and they were significantly different from PTC specimens (P=0.007). There was no significant correlation between PVB19 positivity and tumor stages (P=0.988) and histologic types (P=0.560).
This research, similar to some other studies, showed a significant association between PTC and PVB19 positivity. For the first time, we showed that no significant relationship existed between PVB19 positivity and tumor stages and histologic types. Further investigations are needed to evaluate the relationship between this virus and PTC.

Risk of ovarian malignancy algorithm (ROMA) combining human epididymis secretory protein 4 (HE4) and CA125 is a novel score, specific for epithelial ovarian cancer (EOC).

Our cohort prospective study aimed to evaluate the role of HE4 and ROMA score in the diagnosis of EOC. We determined CA125 and HE4 serum levels in 56 premenopausal women with ovarian mass (38 women with benign ovarian mass and 18 women with malignant ovarian mass), 56 postmenopausal women with ovarian mass (20 women with benign ovarian mass and 36 women with malignant ovarian mass), and 56 healthy women as control.

Serum CA125 and HE4 and ROMA score were significantly higher among postmenopausal group compared with premenopausal and control groups (P< 0.001), and the median serum CA125 and HE4 and ROMA levels were statistically higher among malignant lesions compared with benign lesions and control group (P< 0.001). The sensitivity and specificity of HE4 and ROMA vs. CA125 in discriminating ovarian cancer from benign ovarian tumor was (88% and 98% vs. 90%) and (97% and 99% vs. 80%), respectively. ROMA had better sensitivity and specificity compared to CA125 and HE4 in premenopausal and postmenopausal women (P <0.001) In premenopausal patients, there was a statistically significant difference regarding the area under the curve (AUC) of ROMA vs. CA125 (P=0.004) and ROMA vs. HE4 (P =0.02).

ROMA score showed a better performance in comparison with either CA125 or HE4 alone in premenopausal patients. HE4 and ROMA score significantly differentiated early from late stage ovarian cancer.

Recent evidence underscores to the important regulatory roles of microRNAs as a biomarker for diagnosis of non-small cell lung cancer (NSCLC); this disease often has poor prognosis, and it is the most prevalent cause of cancer-related mortality worldwide. This study investigated the levels of miR-146a-5p and miR-196a-2 in peripheral blood mononuclear cells (PBMC). In the present case-control research, we collected the PBMCs through isolating blood from 22 NSCLC patients and 22 healthy individuals. Following the extraction of total RNA and cDNA synthesis, we studied the expression levels of miR-146a and miR-196a-2 by using qPCR. Both the miR-146a-5p and miR-196a-2 were significantly down-regulated in the PBMCs of NSCLC patients in comparison with normal healthy ones (P=0.002 and p <0.001, respectively). There was an association between the expression levels of microRNAs and the types of tumors, which was significant for miR-146a-5p (P=0.02). Furthermore, in NSCLC cases, a significant positive correlation existed between miR-196a-2 and miR-146a-5p expression levels (r=0.71, P=0.002). According to the study results, miR-146a-5p and miR-196a-2 that were down-regulated in the PBMCs of NSCLC patients might serve as potential biomarkers for diagnosis if confirmed in future studies.

Early and accurate detection of breast cancer reduces the mortality rate of breast cancer patients. Decision-making systems based on machine learning and intelligent techniques help to detect lesions and distinguish between benign and malignant tumours.
In this diagnostic study, a computerized simulation study is presented for breast cancer detection. A metaheuristic optimization algorithm inspired by the bubble-net hunting strategy of humpback whales is employed to select and weight the most effective features, extracted from microscopic breast cytology images, and optimize a support vector machine classifier. Breast cancer dataset from UCI repository was utilized to assess the proposed method. Different validation techniques and statistical hypothesis tests (t-test and ANOVA) were used to confirm the classification results.
The accuracy, precision, and sensitivity metrics of the models were computed and compared. Based on the results, the integrated system with a radial basis function kernel was able to extract the fewest features and result in the most accuracy (98.82%). According to the tests, in comparison with genetic algorithm (GA) and particle swarm optimization (PSO), the WOA based system selected fewer features and yielded higher classification accuracy and speed. The statistical validation of the results further showed that this system outperformed the GA and PSO in some metrics. Moreover, the comparison of the proposed classification system with other successful systems indicated the former’s competitiveness.
The proposed classification model had superior performance metrics, less run time in simulation, and better convergence behaviour owing to its enhanced optimization capacity. Use of this model is a promising approach to develop a reliable automatic detection system.

Prostate cancer is a major malignancy worldwide among men; it is the fourth leading cancer in both genders. This study investigated the pathologic factors of radical prostatectomy (RP) specimens.

About 578 men underwent RP during five years in Shiraz University hospitals. We recorded the following clincopathological parameters: tumor type and stage, Gleason score (GS), grade, tertiary pattern, ISUP, surgical margin, lymph node (LN) involvement, lymphovascular invasion, seminal vesicle involvement, extraprostatic extension (EPE), vas deferens invasion, perineural and pseudocapsular invasion, bladder neck involvement, and age.

The mean age of participants was 63.87 ± 6.95 years. Most had pathologic T2N0Mx (73 %) diseases; the most GS was low-risk GS ≤ 6 (47.4%). Surgical margin status was free of tumors in 72.5% and among those with positive margins; the most involved site was the apex in 18.3%. Single and dual LN involvements were the most prevalent patterns. 5.9% of the patients had EPE. We found perineural and pseudocapsular invasions in 59.9% and 29.9%, respectively. There was a strong correlation between the clincopathological parameters, stage, and ISUP. Perineural invasion, pseudocapsular invasion, and tertiary pattern 5 increased with advanced age (P < 0.0001). The GS 8 to 10 increased with the increase in age (P =0.001).

A strong correlation existed between the clincopathological parameters, stage, and ISUP. Additionally, perineural and pseudocapsular involvement and tertiary pattern 5 had a strong relationship with advanced age.

Lung cancer is one of the most common cancers worldwide. Despite the progression in screening and diagnostic methods, the prevalence and mortality rates of this cancer have not decreased in recent decades. Recent evidence has implied the possible roles of miR-212, miR-124a, miR-125b, miR-27a, and miR-133b in carcinogenesis process. Hence, we examined the changes in the expression level of these microRNAs (miRNAs) during carcinogenesis determined the possible application of these factors as diagnostic or prognostic biomarkers for non-small cell lung cancer (NSCLC). 50 NSCLC patients participated in this descriptive case-control study. During bronchoscopy, we collected their tumor and adjacent normal tumor-free tissues. We further extracted the total RNA from the cells, synthetized cDNA, and examined the expression level of target miRNAs by quantitative real-time PCR. Subsequently, we analyzed the expression levels of these genes and their correlation with clinicopathologic features of patients. The output data of our study showed a statistically significant deregulation in miR-212 (P= 0.002), miR-124a (P=0.001), miR-125b (P= 0.023), miR-27a (P=0.012), and miR-133b (P= 0.05). Moreover, the expression levels of these miRNAs had significant correlations with metastasis, lymph node involvement, tumor cell differentiation degree, and tumor size of NSCLC patients. All of the studied miRNAs could potentially be used as diagnostic or prognostic biomarkers.

Evidence shows that exposure to passive smoking increases the risk of breast cancer. However, there is a lack of data on the role of serum cotinine level among passive smoker women with breast cancer. The purpose of this study was to investigate the association of serum cotinine level and passive smoking exposure with the risk of breast cancer.
We conducted this case-control study on 78 women with newly diagnosed breast cancer and 83 healthy women, aged 21 to 59 years. Neither cases nor controls were ever smokers in their lifetime. The serum cotinine level, as a biological marker of secondhand smoking, was assessed among women exposed to passive smoking.
The mean serum cotinine concentrations were higher among cases compared to controls although the difference was not statistically significant (4.6 ± 3.5 ng/mL vs. 2.8 ± 2.2 ng/mL, respectively, P = 0.059). However, serum cotinine significantly increased the risk of breast cancer (OR = 1.22; 95% CI = 1.02, 1.48, P = 0.034). Exposure to passive smoking at home and exposure from a smoker husband increased the risk of breast cancer compared with those with no exposure (OR = 2.17; 95% CI = 1.15, 4.08, P = 0.016; and OR = 2.67; 95% CI = 1.35, 5.29, P = 0.005, respectively).
Serum cotinine levels and passive smoking exposure appeared to be independent risk factors associated with the development of breast cancer.

Mucinous breast carcinoma (MBC) is a subtype of breast cancer categorized by the presence of extracellular mucin and has more favorable prognosis than invasive carcinoma of no special type of breast cancer. The present study incorporates 27 years of practical experience from a breast disease research center-based series of cases regarding MBC and invasive ductal carcinoma (IDC). In this retrospective study, we studied the medical documents of 7,739 patients in the Breast Disease Research Center, Shiraz University of Medical Sciences, from December 1993 to January 2019. TNM data, demographic status, pathologic stage, histological grade, hormonal receptor data, recurrence, overall survival (OS), and disease-free survival (DFS) were reviewed. We also statistically evaluated the clinical and histopathological differences of pure, mixed MBC, and IDC using SPSS, version 21.0 (IBM, USA). P<0.05 was considered as statistically significant. A total of 78 and 31 patients were observed to have pure and mixed MBC, respectively, and 5,774 breast cancer patients had IDC. The pure MBC group showed a lower histological grade and pathologic stage and a larger tumor size compared with mixed MBC (P<0.001). The pure MBC patients had significantly less perinural and lymphovascular invasion and had less HER-2 positive status in comparison with IDC patients (P=0.023). The DFS and OS did not differ the between groups. MBC is a rare diagnosis with a favorable prognosis due to low lymph node metastases.

We aimed to analyze the prognostic impact of mucinous and non-mucinous rectal adenocarcinoma with stage II and III rectal carcinoma treated with radical surgery plus (neo) adjuvant chemoradiotherapy and evaluate disease-free (DFS) and overall survival (OS).

We conducted this retrospective study on patients with pathologically proven stage II/III rectal carcinoma and treated in the Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital between January 2008 and December 2013. We designed a clinical abstract sheet and reviewed all cases in terms of history, clinical assessment, investigations done on the patients, and pathological reports including all the details, and treatment modalities, namely neoadjuvant and adjuvant.

The median DFS for non-mucinous adenocarcinoma (NMC) was beyond 60 months, while that for mucinous adenocarcinoma (MA) was 24 months (P=0.008). The median OS for NMC was beyond 60 months; whereas, the mean OS of MA was 25 months (P=0.002).Therefore, the difference between both groups was statistically significant regarding DFS and OS. Pathological subtype was the only statistically significant independent predictor in the three-year DFS. However, pathological subtype and lymph-vascular invasion were statistically significant independent predictors in the three-year OS.

Histological subtype was an independent prognostic factor for both DFS ans OS in patients with stages II and III rectal carcinoma.

Cervical cancer patients undergoing chemo-radiotherapy experience considerable amounts of stress. In the present study, we attempted to ascertain the effectiveness of yoga nidra, a mind-based structured relaxation exercise, in mitigating the stress. We conducted this prospective two-arm study on 48 volunteers randomly allocated into experimental (n=24) and control groups (n=24) using simple random sampling (lottery method). We collected the pretest data using a stress scale. The experimental group was then provided with yoga nidra sessions during the course of the treatment. We collected the post-test data using the same tool at the end of the radiation treatment with 50 Gy (2 Gy for five days a week for five consecutive weeks). We presented the demographic details in frequency and percentage and analyzed the stress data using ANOVA with Tukey’s multiple comparison test. P<0.05 was considered as significant. The volunteers in both cohorts experienced moderate to severe stress at the beginning of the study. Compared to the control group, the stress was significantly less in the groups that practiced yoga nidra (79.46 vs. 64.42) (P<0.0001). The results of the study clearly suggested that yoga nidra was effective in reducing the stress in cervical cancer patients undergoing curative radiation therapy.

We aimed to achieve full tumor control during every fraction with head and neck cancer patients using 3DCRT treatment technique. We divided 16 head and neck cancer patients into two groups to deliver radiotherapy doses of 66Gy and intensity modulated radiotherapy (IMRT) 70Gy. We applied 3DCRT plan as a forward IMRT plan for each patient with coplanar beams arrangement technique designed with angles of (0o, 60o, 90o, 180o (or around 175o and 185o), 270o and 300o).We assessed the plans according to DVHs and satisfactory dose distributions. Based on the overall evaluation of the two groups (16 cases), we achieved an accepted dose distribution for PTVs and OARs dose; simulating IMRT inverse plans dose distribution. Using such a mono-isocenteric plan, we were able to achieve a perfect uniform dose distribution for PTVs up to 70Gy, while sparing critical organs. This template could be used in countries with no access to forward IMRT planning.

Young women with breast cancer have been reported to present more aggressive clinical and pathological features, requiring more treatment options compared with older patients. Our objective was to investigate the clinicopathological features of breast cancer in our local young women.

We conducted an observational descriptive study on 100 young women (age ≤ 40) with breast cancer. The subjects were taken care of, at a single tertiary cancer facility, from mid-2007 to mid-2014. We reviewed the clinicopathological profiles and therapeutic strategies.

Ratio of breast cancer in young women was about 13% of all breast cancer patients. The mean age of the patients was 35 years ± 4SD. 56% of the patients had grade III tumors and 46% were in stage III. Hormonal receptors were positive in 70%, while HER2 was positive in 26%. 70% of the patients underwent modified radical mastectomy, 96% received chemotherapy, and 70% received radiotherapy and required hormonal therapy.

This review showed that breast cancer in our local young women was largely diagnosed at advanced stages with more aggressive clinico-pathological features. Moreover, most of the patients received more aggressive treatment options. Therefore, physicians should pay a close attention to breast lumps in young women.

Chronic myeloid leukemia (CML) is a common type of cancer. Leukemia is associated with diverse molecular and genetic changes, including loss and gain of chromosomes, gene deletions, duplications, point mutations, and gene fusions derived from chromosomal translocations. Advanced genetic tests are done to diagnose leukemia; however, many patients are not diagnosed because many of the symptoms are vague, unspecific, and referable to other diseases.

Following the extraction of genomic DNA from CML patient, we performed exome sequencing. Variants were detected via GATK software. Novel alterations in CML cases were then visualized in the integrated genome browser. To enrich our findings, we included exome sequencing data pertaining to 11 individuals. The data was deposited in the ENA database in our analysis. Afterwards, we verified insertion in the ATXN3 gene through performing PCR reactions for both healthy and CML cases.

We identified an alteration in the genomic sequence of the ATXN3 gene in the CML cases.

A correlation existed between insertion in the ATXN3 gene and positive CML cases. These findings might be conducive to the detection of CML at the early stages of the disease.

Lutein and its isomerzeaxanthin are safe natural compounds. They are able to reduce the development of tumor and other chronic diseases. The objectives of the current study was to examine the cytotoxicity of lutein isolated and purified from alfalfa, safe and low-cost plant, on five different human cancer cell lines, namely (MCF-7), (HepG2), (A549), (PC3), and (HCT116), as well as normal (HFB4) cells.

We examined the cytotoxicity of lutein purified from Medicago sativa L and evaluate its activity against human liver HepG2, breast MCF-7, lung A549, prostate PC3, and colon HCT116 cancer cell lines using SRB assay in comparison with doxorubicin as a reference drug.

Results revealed that the tested extract could be a more promising anticancer agent in the case of MCF-7 (IC50, 3.10±0.47 μg/ml) compared with standard drug doxorubicin (IC50, 2.90±0.30 μg/ml). Moreover, the extract showed a moderate effect on HepG2 (IC50, 6.11±0.84 μg/ml) versus doxorubicin (IC50, 2.90±0.30 μg/ml); meanwhile, the extract showed no activity against A549, PC3, and HCT116 cells. The results further revealed that the extract had no toxicity against the growth of normal HFB4 cells versus doxorubicin.

Lutein-rich extract from alfalfa had a major antiproliferative role in breast MCF-7 and liver HepG2 compared to doxorubicin.

With a prevalence of approximately 1 out of 2,500 to 4,000 births, neurofibromatosis type 1 (NF1), also known as von Recklinghausen’s disease, is one of the most prevalent autosomal dominant diseases in humans. There is four to five-fold increased risk of malignancy in these patients due to the presence of NF1 gene mutation, which is a tumour suppressor inhibiting RAS activation. NF1 is known to be closely associated with central nervous system (CNS) tumours; however, its association with other non-CNS malignancies is not uncommon. Mutation of BRCA1 (breast cancer 1, early onset) and BRCA2 (breast cancer 2, susceptibility protein) genes has long been recognized as an important risk factor for the develpoment of breast cancer. Incidentally, BRCA1 and NF1 genes are both located in the long arm of chromosome 17. The association between NF1 and breast cancer has long been debated; recent studies, on the other hand, have established this association, with NF1 unequivocally identified as breast cancer susceptibility gene conferring a moderate risk of breast cancer development. In this report, we described multimodality imaging features of breast cancer in two women with NF1; we further reviewed the literatures on the association between NF1 and breast cancer and its diagnostic challenge.