الفهرس 
Literature ReviewOnly 14 pages are availabe for public view
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Abstract
Cancer is considered one of the leading causes of death worldwide. It is largely resulting from the genetic mutations that consequently lead to inheritance of information based on gene-expression levels (epigenetics). Oxidative stress clearly has a role in carcinogenesis and the antioxidant enzymes categorized as the most important defense modalities against cellular proliferation and tumor infiltration. According to Globocan estimates, BC, CRC and HCC belong to the most common types of cancerous diseases in both sexes in developed countries. BC is a worldwide health problem notably in women. This cancer type is rated as the second most common cancer. It was reported that the tissues in BC patients are heterogeneous in regard to quantitative and/or qualitative variation in protein patterns. There was a clear decline in the expression of some proteins among BC patients. CRC is considered as the most common type of gastrointestinal cancers. It is the most malignant tumor with very high morbidity and mortality rates and poor prognosis. HCC is categorized as the seventh most common form of cancer in men worldwide and the ninth most common in women. Development of this type of cancer is closely associated with chronic liver diseases.
1. Clinical and biochemical diagnosis of BC, CRC and HCC and criteria for patients selection
During the BC diagnosis, it was found that diabetes and hypertension were diagnosed in 20.00 % of the patients (age 53.53 ± 1.85 years). The tumor type was invasive duct II in 73.33% and invasive duct III in 26.67% of BC patients. The tumor sized was <5 Cm in 60.00% and >5 Cm in 40.00% of the patients. TNM staging revealed the tumor stage that categorized into stage II (20.00%) and stage III (80.00%). Moreover, ER/PR was negative in 80.00% and positive in 20.00% of patients.
During the HCC diagnosis, it was found that all HCC patients (age 62.47 ± 2.02 years) infected by HCV (not HBV). The hematological measurements were quantified during clinical diagnosis and represented by Hb (11.45 ± 0.41 g/dl), WBCs (5.75 ± 0.16 X 103/L) and PLT (157.00 ± 6.00 X 109 /L). The liver factors were represented by ALT (63.93 ± 3.24 U/L), AST (70.77 ± 2.91 U/L), ALP (159.00 ± 4.30 U/L), GGT (60.93 ± 1.36 U/L), albumin (3.93 ± 0.17 g/dl), bilirubin (total 1.34 ± 0.12 mg/dl and direct 0.34 ± 0.05 mg/dl), PT (75.33 ± 0.64%), PC (82.00 ± 1.22%) and INR (1.26 ± 0.02) in addition to AFP (1342.93 ± 3.97 ng/dl). The kidney functions were represented by urea (6.66 ± 0.38 mg/dl) and creatinine (1.02 ± 0.06 mg/dl). It was noticed that liver was enlarged in size in 53.33%, shrunken in 13.33% and average in 33.33% of the patients. The thrombosis occurred in liver PV in 33.33% of patients. All patients were diagnosed at the cirrhotic stage and this was supported by liver Echo. The moderate ascites were noticed in 13.33%, mild in 20.00% and marked in 6.67%. No ascites were identified in the other 60.00% of patients. Furthermore, the metastasis was identified in portal hepatic and pancreaticoduodenal LMNS in 6.67% of HCC patients.
As regard to the CRC patients (age 54.27 ± 2.84 years), it was found that the obese CRC patients represented 26.67% of all CRC patients. They were diagnosed based on the hematological measurements that were represented by Hb (8.29 ± 0.16 g/dl), WBCs (6.93 ± 0.64 X 103/L), PLT (183.87 ± 4.19 X 109 /L) and ESR (84.73 ± 1.25 mm/h) in addition to the specific tumor markers (CEA), CA 19-9 and AFP). In addition, the CT revealed various malignant abnormalities represented by rectal mass lesion (about 5 Cm), multiple LNs metastasis, circumferential wall thickening at proximal ascending colon, multiple small LNs Paracolic, localized caecal mass (about 4 x 6 Cm), pracolic LNS metastasis, diffuse circumferential rectal mass lesion, heptic flexur circufencial mass lesion, rectal mass lesion and regional LNS enlargement in addition to diffuse rectal wall mass lesion, small paracolic LNs. The abd US showed marked colonic distension, bright hepatomegaly, parenchymal liver disease and hepatomegaly with multiple deposits in addition to mild splenomaegaly. The colonoscopy illustrated various abnormalities represented by small ulcer with elevated edges at the cecum (2 Cm), large rectosigmoid mass lesion causing partial obstruction, small fungating mass lesion at the ascending colon, fungting obstructing distal rectal and small rectal lesion, polypoidal rectal mass (about 4 Cm), large malignant looking ceacal ulcer about 4 Cm, rectal mass lesion with superficial ulcerateion, large deep ulcer at transverce colon (malignant ulcer). This diagnosis was supported by the pathological examination that confirmed presence of ulcerating, tubulovillus and mucoid infiltrative adenocarcinoma.
It was found that level of the TAC and TPC concentration elevated significantly (P≤0.05) in sera of BC, CRC and HCC patients as compared to control group. The TAC level was higher and TPC level lower in sera of CRC and HCC patients significantly (P≤0.05) than BC patients. On the other hand, it was found that activities of the antioxidant enzymes (CAT and GPx) were significantly (P≤0.05) lower in sera of BC, CRC and HCC patients as compared to control group. As compared to the BC patients, activities of theses enzymes were noticed higher in sera of CRC and HCC patients. No significant changes were noticed in levels of all these measurements (TAC, TPC, CAT and GPx) in HCC patients when compared to the CRC patients.
2. Electrophoretic (epigenetic) correlation among patients with BC, CRC and HCC with comparison to control (healthy) individuals
2.1. Native electrophoretic protein pattern
The electrophoretic pattern revealed that 4 common bands were identified at Rfs 0.21, 0.35, 0.44 and 0.75. Only one characteristic band was identified in sera of BC patients at Rf 0.96 (Mwt 4.81 KDa ; B% 12.03). In BC patients, the alterations were detected through hiding one normal band with appearance of 2 abnormal ones identified at Rfs 0.62 and 0.96 (Mwts 17.06 and 4.81 KDa ; B% 14.94 and 12.03, respectively). Therefore, the SI% value decreased with increasing the GD% value (SI%= 76.92% ; GD%= 23.08%). In CRC patients, the alterations were represented by hiding one normal band with appearance of abnormal one identified at Rf 0.61 (Mwts 17.23 KDa and B% 17.04). Therefore, the SI% value decreased with increasing the GD% value (SI%= 83.33% ; GD%= 16.67%). In HCC patients, the disturbances were represented by hiding one normal band with appearance of abnormal one identified at Rf 0.61 (Mwts 17.10 KDa and B% 18.05) and this leads to decreasing the SI% value with increasing the GD% value (SI%= 83.33% ; GD%= 16.67%). The BC, CRC and HCC patients were physiologically similar to control group by 76.92, 83.33 and 83.33%, respectively. Both of the CRC and HCC patients were qualitatively similar to BC patients by 76.92%. The HCC patients were completely similar to the CRC patients (SI= 100%). Moreover, it revealed that 3 common bands were identified at Rfs 0.14, 0.30 and 0.41. Two characteristic bands were identified in sera of CRC patients at Rfs 0.12 and 0.24 (Mwts 152.29 and 63.43 KDa ; B% 9.20 and 9.34, respectively) and 2 characteristic bands identified in sera of HCC patients at Rfs 0.50 and 0.84 (Mwts 21.55 and 8.82 KDa ; B% 19.42 and 24.64, respectively). In BC patients, the alterations in protein pattern were detected through hiding one normal band with appearance of abnormal one identified at Rf 0.47 (Mwt 24.35 KDa ; B% 13.91). Therefore, the SI% value decreased with increasing the GD% value (SI%= 87.50% ; GD%= 12.50%). In CRC patients, the alterations were represented by hiding one normal band with appearance of the characteristic bands that were identified in sera of CRC patients at Rfs 0.12 and 0.24 (Mwts 152.29 and 63.43 KDa ; B% 9.20 and 9.34, respectively). Therefore, the SI% value decreased with increasing the GD% value (SI%= 77.78% ; GD%= 22.22%). In HCC patients, the abnormalities were detected through hiding 5 normal bands with appearance of the characteristic bands that were identified at Rfs 0.50 and 0.84 (Mwts 21.55 and 8.82 KDa ; B% 19.42 and 24.64, respectively). The SI% value decreased with increasing the GD% value (SI%= 46.15% ; GD%= 53.85%). The BC, CRC and HCC patients were physiologically similar to control group by 87.50, 77.78 and 46.15%, respectively. Both of the CRC and HCC patients were qualitatively similar to BC patients by 77.78 and 46.15%, respectively. The HCC patients were similar to the CRC patients by 40.00%. At quantitative level, it was found that quantities of the total protein bands declined significantly (P≤0.05) in the BC, CRC and HCC patients as compared to control group. It increased in the CRC patients and decreased in HCC patients significantly (P≤0.05) as compared to the BC patients. It decreased significantly (P≤0.05) in HCC patients when compared to CRC patients.
2.2. Native electrophoretic lipid moiety of native protein
Two common bands were identified at Rfs 0.39 and 0.81. One characteristic band was identified in sera of healthy individuals at Rf 0.30 (B% 8.56), one characteristic band identified in BC patients at Rf 0.33 (B% 10.81) and one characteristic band identified in CRC patients at Rf 0.29 (B% 15.35). In BC patients, the alterations in the lipid moiety of native protein were represented by hiding 4 normal band with appearance of 4 abnormal ones identified at Rfs 0.13, 0.17, 0.33 and 0.96 (B% 6.68, 6.96, 10.81 and 24.34, respectively). Therefore, the SI% value decreased with increasing the GD% value (SI%= 42.86% ; GD%= 57.14%). In CRC patients, the alterations were detected through hiding 4 normal bands with appearance of 3 abnormal ones identified at Rf 0.16, 0.29 and 0.96 (B% 13.23, 15.35 and 17.11, respectively). The SI% value decreased with increasing the GD% value (SI%= 46.15% ; GD%= 53.85%). In HCC patients, the abnormalities were detected through hiding 3 normal bands with existence of abnormal one identified at Rf 0.13 (B% 18.08). The SI% value decreased associated with increasing the GD% value (SI%= 66.67% ; GD%= 33.33%). The BC, CRC and HCC patients were physiologically similar to control group by 42.86, 46.15 and 66.67%, respectively. Both of the CRC and HCC patients were qualitatively similar to BC patients by 61.54 and 50.00%, respectively. The HCC patients were similar to the CRC patients by 54.55%. Quantitatively, it was noticed that quantities of the total lipoprotein bands declined in the BC and increased in the CRC patients significantly (P≤0.05) with respect to control. As compared to BC patients, it increased in the CRC and HCC patients. It declined in HCC patients when compared to CRC patients.
2.3. Electrophoretic calcium moiety of native protein
Two common bands were identified at Rfs 0.44 and 0.92. No characteristic bands were identified. In BC patients, the alterations in calcium moiety of native protein pattern were represented by hiding one normal band without existence of abnormal bands. The SI% value decreased with increasing GD% value (SI%= 85.71% ; GD%= 14.29%). In CRC patients, the abnormalities were represented by hiding one normal band with appearance of one abnormal band at Rf 0.32 (B% 22.86). The SI% value decreased with increasing GD% value (SI%= 75.00% ; GD%= 25.00%). In HCC patients, the alterations were detected through hiding one normal band with appearance of one abnormal band at Rf 0.30 (B% 21.28). Therefore, the SI% value decreased with increasing the GD% value (SI%= 75.00% ; GD%= 25.00%). The BC, CRC and HCC patients were similar to control by 85.71, 75.00 and 75.00%, respectively. Both of the CRC and HCC patients were similar to BC patients by 57.14%. The HCC patients were completely similar to the CRC patients (SI%= 100.00%). At quantitative level, it was found that quantities of the total bands declined significantly (P≤0.05) in BC, CRC and HCC patients. As compared to BC patients, it decreased in CRC and HCC patients. Also, it decreased in HCC patients when compared to the CRC patients.
2.4. Electrophoretic isoenzymes
2.4.1. Electrophoretic Catalase (CAT) pattern
Only one common band was identified at Rf 0.40. One characteristic band was identified in sera of BC patients at Rf 0.23 (B% 18.23). In BC patients, the alterations were represented in this isoenzyme pattern by hiding 2 normal types with existence of one abnormal (characteristic) band at Rf 0.23 (B% 18.23). Therefore, the SI% value decreased with increasing the GD% value (SI%= 60.00% ; GD%= 40.00%). In CRC patients, the alterations were represented by hiding 2 normal types with appearance of one abnormal band at Rf 0.87 (B% 29.87). The SI% value decreased with increasing the GD% value (SI%= 66.67% ; GD%= 33.33%). In HCC patients, the alterations were represented by hiding 3 normal types without existence of abnormal ones. The SI% value decreased with increasing GD% value (SI%= 57.14% ; GD%= 42.86%). The BC, CRC and HCC patients were physiologically similar to control group by 60.00, 66.67 and 57.14%, respectively. Both of CRC and HCC patients were similar to BC patients by 66.67 and 28.57%, respectively. The HCC patients were similar to CRC patients by 66.67%. Quantitatively, it was found that quantities of the total CAT types declined in BC, CRC and HCC patients significantly (P≤0.05) as compared to healthy group. It declined in CRC and HCC patients as compared to the BC patients. Also, it declined in HCC patients as compared to the CRC patients.
2.4.2. Electrophoretic Peroxidase (POX) pattern
No common bands were identified. Only one characteristic band was identified in sera of HCC patients at Rf 0.63 (B% 20.75). In BC patients, the alterations in POX isoenzyme pattern were represented by hiding the normal types (8 types) with existence of 2 abnormal types identified at Rfs 0.52 and 0.88 (B% 48.77 and 51.23, respectively). Therefore, the SI% value decreased and reached the lowest value with increasing the GD% value (SI%= 0.00% ; GD%= 100.00%). In CRC patients, the alterations were represented by hiding 6 normal types with existence of 2 abnormal bands identified at Rf 0.52 and 0.89 (B% 27.79 and 24.87, respectively). The SI% value decreased with increasing the GD% value (SI%= 33.33% ; GD%= 66.67%). In HCC patients, the alterations were represented by hiding 6 normal types with appearance of 3 abnormal types identified at Rfs 0.53, 0.63 and 0.88 (B% 21.68, 20.75 and 23.17, respectively). The SI% value decreased associated with increasing the GD% value (SI%= 30.77% ; GD%= 69.23%). The BC, CRC and HCC patients were qualitatively identical to control group by 600.00, 33.33 and 30.77%, respectively. Both of the CRC and HCC patients were similar to BC patients by 66.67 and 57.14%, respectively. The HCC patients were similar to the CRC patients by 88.89%. Quantitatively, it was noticed that quantities of the total POX types declined in BC patients significantly (P≤0.05) as compared to healthy group. It elevated in CRC and HCC patients as compared to BC patients.
2.4.3. Electrophoretic α-Esterase (α-EST) pattern
There was one common band identified at Rf 0.85 and one characteristic band identified in sera of BC patients at Rf 0.47 (B% 31.57). In BC patients, the alterations in the α-EST isoenzyme pattern were represented by hiding 4 normal types with existence of 2 abnormal bands identified at Rfs 0.16 and 0.47 (B% 31.82 and 31.57, respectively). The SI% value decreased with increasing the GD% value (SI%= 25.00% ; GD%= 75.00%). In CRC patients, the alterations were represented by hiding 2 normal types with existence of one abnormal band identified at Rf 0.16 (B% 30.95). The SI% value decreased with increasing the GD% value (SI%= 50.00% ; GD%= 50.00%). In HCC patients, the alterations were represented by hiding 3 normal types with existence of one abnormal band identified at Rf 0.14 (B% 30.50). The SI% value decreased associated with increasing the GD% value (SI%= 50.00% ; GD%= 50.00%). The BC, CRC and HCC patients were qualitatively similar to control group by 25.00, 50.00 and 50.00%, respectively. Both of the CRC and HCC patients were similar to BC patients by the same similarity degree (SI%= 66.67%). The HCC patients were completely similar (SI%= 100.00%) to the CRC patients. At the quantitative level, quantity of the total α-EST types declined in the BC, CRC and HCC patients significantly (P≤0.05) as compared to healthy group. It declined in the CRC and HCC patients as compared to the BC patients. It was significantly (P≤0.05) higher than that in CRC patients.
2.4.4. Electrophoretic β-esterase (β-EST) pattern
Three common bands were identified at Rfs 0.07, 0.26 and 0.90. Only one characteristic band was identified in sera of BC patients at Rf 0.53 (B% 19.50). In BC patients, the alterations in this isoenzyme pattern were represented by hiding one normal type with existence of one abnormal (characteristic) band identified at Rf 0.53 (B% 19.50). The SI% value decreased with increasing the GD% value (SI%= 80.00% ; GD%= 20.00%). In CRC patients, no qualitative or physiological alterations were detected. Therefore, the SI% value reached the highest value with lowering the GD% value (SI%= 100.00% ; GD%= 0.00%). In HCC patients, the alterations were represented by hiding 2 normal types without appearance of abnormal types. The SI% value decreased with increasing the GD% value (SI%= 75.00% ; GD%= 25.00%). The BC, CRC and HCC patients were physiologically similar to control group by 80.00, 100.00 and 75.00%, respectively. Both of the CRC and HCC patients were qualitatively similar to BC patients by 80.00 and 75.00, respectively. Moreover, the HCC patients were similar to the CRC patients by 75.00%. Quantitatively, it was noticed that quantity of the total β-EST types enhanced in CRC patients and declined in the HCC patients significantly (P≤0.05) as compared to healthy individuals. It increased in CRC and decreased in HCC patients significantly (P≤0.05) as compared to the BC patients. In HCC patients, it was significantly (P≤0.05) lower than that in CRC patients.
2.4.5. Electrophoretic α-Amylase pattern
No common bands were identified. Only one characteristic band was identified in sera of BC patients at Rf 0.38 (B% 48.09). In BC patients, the alterations in this isoenzyme pattern were represented by hiding the normal types (2 normal types) with existence of 2 abnormal bands identified at Rfs 0.13 and 0.38 (B% 51.91 and 48.09, respectively). The SI% value decreased and reached the lowest value with increasing the GD% value (SI%= 0.00% ; GD%= 100.00%). In CRC patients, the alterations were represented by hiding one normal type with existence of one abnormal band identified at Rf 0.14 (B% 52.29). The SI% value decreased with increasing the GD% value (SI%= 50.00% ; GD%= 50.00%). In HCC patients, the alterations were represented by hiding one normal type with appearance of one abnormal band identified at Rf 0.14 (B% 49.77). The SI% value decreased with increasing the GD% value (SI%= 50.00% ; GD%= 50.00%). The BC, CRC and HCC patients were physiologically similar to control group by 0.00, 50.00 and 50.00%, respectively. Both of the CRC and HCC patients were qualitatively similar to BC patients by the same similarity degree (SI%= 50.00%). The HCC patients were completely similar to the CRC patients (SI%= 100.00%). Quantitatively, it was found that quantities of the total α-amylase types declined in the BC, CRC and HCC patients significantly (P≤0.05) as compared to control group. It increased in HCC patients as compared to BC patients. In HCC patients, it was significantly (P≤0.05) higher than that in CRC patients.
3. Molecular correlation among patients with BC, CRC and HCC with comparison to control (healthy) individuals
3.1. FAS gene expression
It was noticed that the band intensity and relative quantity of the FAS gene increased significantly (P≤0.05) in BC, CRC and HCC patients as compared to healthy individuals. In BC patients, both of the band intensity and relative quantity are higher than that in the CRC. The band intensity in BC patients is higher than that in HCC patients. There is no significant difference the relative band quantity between two groups (BC and HCC). As compared to CRC patients, both of band intensity and relative quantity of this gene were significantly (P≤0.05) higher in HCC patients.
3.2. Interleukin 1β (IL-1β) gene expression
It was found that the band intensity and relative quantity of the IL-1β gene were approximately equal in BC and healthy individuals (non-significant differences). Both of the band intensity and relative quantity in CRC patients were significantly (P≤0.05) higher than that in BC and healthy group. In HCC patients, they declined significantly (P≤0.05) as compared to the other groups (healthy individuals, BC and CRC).
3.3. Interleukin 18 (IL-18) gene expression
It was noticed that there was no significant differences in the band intensity and relative quantity of the IL-18 gene between BC and healthy individuals. In CRC patients, they were significantly (P≤0.05) higher than that in BC and healthy individuals. In HCC patients, they declined significantly (P≤0.05) as compared to the other groups (healthy individuals, BC and CRC).
3.4. Tumor Necrosis Factor-α (TNF-α) gene expression
It was revealed that intensity of TNF-α gene increased significantly (P≤0.05) in BC patients and there was no significant differences in its relative quantity as compared to healthy individuals. Both of the intensity and relative quantity of this gene increased in CRC and HCC patients when compared to BC patients and healthy group. In HCC patients, the band intensity was significantly (P≤0.05) higher than that in BC, HCC patients and healthy individuals. The relative band quantity in HCC patient was significantly (P≤0.05) higher than that in BC patients and healthy individuals. There was no significant difference in the relative quantity between CRC and HCC