Levels of soluble intercellular adhesion molecule-1 and total sialic acid in serum of patients with colorectal cancer

BACKGROUND AND OBJECTIVES: Serum soluble intercellular adhesion molecule-1 (sICAM-1) and total sialic acid (TSA) are related to the metastatic potential of cancer cells. The purpose of the present investigation was to determine sICAM-1 and TSA levels in colorectal carcinoma and correlate their levels with the cancer stage. METHODS: The sera from 65 patients with colorectal cancer (18 at Dukes' B, 24 at Dukes' C, 23 at Dukes' D) were extracted before treatment. The concentrations of sICAM-1 and TSA were measured by enzyme-linked immunoassay and the thiobarbituric acid method, respectively, and compared with those from a healthy control group (n = 42). RESULTS: Mean serum sICAM-1 and TSA levels were found to be higher in the total patient group than in the control group (P < 0.0001). The concentrations of sICAM-1 and TSA were significantly higher in patients with Dukes' C and Dukes' D. The correlations between sICAM-1 and TSA became more significant as the stage of the disease increased (r = 0.58, P < 0.05 in Dukes' B, r = 0.88, P < 0.01 in Dukes' C and r = 0.81, P < 0.01 in Dukes' D). CONCLUSIONS: The results of this investigation indicate that sICAM-1 and TSA are the best of the tested markers. These markers should prove useful for monitoring malignant disease stage and for evaluating the effectiveness of various therapeutic approaches for colorectal carcinomas.     

Evaluation of serum sialic acid, heat stable alkaline phosphatase and fucose as markers of breast carcinoma

Serum levels of total sialic acid (TSA), lipid bound sialic acid (LSA), heat stable alkaline phosphatase (HSAP) and fucose were measured in 39 patients with breast carcinoma, 14 patients with benign breast diseases and 35 healthy female individuals. Elevated levels of the four biomarkers in breast carcinoma were significant when compared with controls (p less than 0.001). Fucose levels were most sensitive (71.8%), while TSA levels were most specific (64.3%) for breast carcinoma. Sensitivity and specificity were 100% when combinations of LSA with fucose and TSA with HSAP were studied respectively. LSA was significantly elevated in infiltrating duct carcinoma patients compared with lobular carcinoma (p less than 0.001). TSA, HSAP and fucose also had lower mean values in lobular carcinoma as compared to infiltrating duct carcinoma. Increase in the levels of LSA and HSAP after surgical removal of the tumor in breast carcinoma occurred prior to the clinical evidence of the recurrence. The results indicate that the combination of the markers studied might be useful in breast cancer diagnosis and treatment monitoring.     

Five tumor markers in lung cancer: significance of total and "lipid"-bound sialic acid.

Total sialic acid (TSA) and "lipid-bound" sialic acid (LSA) were evaluated in comparison to carcinoembryonic antigen (CEA) and ferritin and neuron specific enolase (NSE) in 152 untreated patients with primary lung cancer, 107 benign pulmonary disease patients and 207 notmal controls. The mean concentrations of TSA, LSA and CEA in lung cancer patients, were significantly higher than in benign and normal controls (p less than 0.001), while the mean ferritin and NSE levels were significantly higher than in normal controls only (p less than 0.001). At the designated cut-off serum levels, sensitivities of the five markers for lung cancer were in decreasing order: TSA 86.5% (greater than 80 mg/dL), LSA 77% (greater than 20 mg/dL), CEA 46.4% (greater than 5 ng/mL), ferritin 36% (greater than 300 ng/mL) and NSE 34.5% (greater than 12.5 ng/mL). Using the benign pulmonary values as negative controls the specificity of each marker was as follows: CEA 88%, ferritin 72%, NSE 58%, TSA 44% and LSA 44%. In small cell lung cancer (SCLC) patients, NSE mean concentrations and sensitivity were significantly higher than in non-small lung cancer (NSCLC) patients (9.63 +/- 4.4 versus 23.54 +/- 16.9, p less than 0.001 and 74% versus 21.4% respectively). While in NSCLC patients only CEA levels correlated well with the stage of the disease, in SCLC patients concentrations of TSA, LSA and ferritin were significantly higher in extensive than in limited disease stages. These preliminary data suggest that, although TSA and LSA are highly sensitive markers in lung cancer, their specificity is low.     

Serum glycoconjugates in patients with anemia and myeloid leukemia

Because of carbohydrate alterations in malignant cells, serum glycoproteins have drawn considerable attention. In the current investigation we determined total sialic acid (TSA), lipid bound sialic acid (LSA), protein bound hexoses (galactose + mannose), fucose, hexosamines (galactosamine + glucosamine) and mucoid protein concentrations in the serum of patients with anemia and myeloid leukemia. The results were compared with those obtained in healthy individuals. In the leukemia patients we observed significant increases in glycoconjugates compared with the controls (P less than 0.001), and in TSA and fucose levels compared with the anemia patients (P less than 0.001). LSA and hexosamine levels were significantly lower in anemia patients with respect to the leukemia patients (P less than 0.01 and P less than 0.05 respectively), whereas levels of mucoid proteins and hexoses did not show significant differences. Except for hexosamines, all the markers tested were significantly elevated in the anemia patients compared with the controls. The present study suggests that the glycoconjugates investigated might be useful biochemical markers for differentiating anemic from leukemic conditions.     

Diagnosis Value of Membrane Glycolipids Biochemistry Index in Intracranial and Gastrointestinal Tumors

The diagnostic value of membrane glycolipid biochemistry index, the lipid-bound sialic acid (LSA) and totalsialic acid (TSA) in cerebrospinal fluid (CSF) was evaluated in 30 intracranial and 65 gastrointestinal tumors.The plasma LSA, TSA and red cell membrane sialic acid (R-SA) in were determined according to the method ofSevenmerhulm. Our results showed that the levels of LSA and TSA in CSF of intracranial tumor patients washigher than that of normal group(p<0.01). The concentration of TSA and LSA in patients with malignant gliomawas higher than that of benign meningioma patients(P<0.01). No significance was found between intracranialhalmatoma patients and normal control group for levels of membrane glycolipids (p>0.05). Results also found thatthe plasma LSA, TSA and R-SA of gastric carcinoma were significantly higher than those of control group (p<0.05);while no significant difference was found in the plasma LSA, TSA and R-SA levels between chronic gastritis,gastrohelcoma and normal control group (p>0.05). Plasma LSA, TSA and R-SA levels of gastric carcinoma patientwere significantly higher than those of chronic gastritis patients and gastrohelcoma patients(p<0.05). It was alsofound that plasma LSA, TSA and R-SA contents were significantly higher in large intestine carcinoma patientsthan in benign in stestine tumor patients (p<0.05) while no significant difference was found between intestinebenign tumor and normal control group (p>0.05). The levels of LSA, TSA and R-SA were obviously higher inthe patients with metastasis than in the ones without (p<0.05.) The membrane glycolipid biochemistry indexLSA and TSA in CSF are sensive markers for diagnosing intracranial tumors. For gastrointestinal malignanttumors the plasma LSA TSA and red blood cell membrane SA may be considered as auxiliary indicators fordiagnosis. They can be used for distinguishing benign from malignant tumors.     

血清唾液酸检测对癌症诊断的临床价值

作者测定了５７７例正常人和２４１例恶性肿瘤患者血清总唾液酸（ＴＳＡ）和血清脂质结合唾液酸（ＬＳＡ）的含量。结果表明：ＴＳＡ和ＬＳＡ的含量变化与疗效一致，治疗有效者ＴＳＡ和ＬＳＡ与正常人相比，均无显著性差异（Ｐ＞０．０５）；治疗无效（包括未经治疗）者与正常人相比除原发性肝癌、乳腺癌外均有显著性差异（Ｐ＜０．０１）。血清ＴＳＡ和ＬＳＡ测定对肺癌、胃癌、大肠癌等有临床诊断价值（Ｐ＜０．０１），对鼻咽癌诊断效果更好（Ｐ＜０．００１）。对肝癌、乳腺癌的诊断价值有限（Ｐ＞０．０５）。恶性肿瘤患者ＴＳＡ与ＬＳＡ含量间无相关关系（ｒ＝０．０９；Ｐ＞０．０５；ｎ＝１１７）。ＬＳＡ检测不能代替ＴＳＡ检测，两者应该联合检测以提高其阳性率。     

Total and lipid-bound sialic acid in the cerebrospinal fluid of patients with brain tumors

Total sialic acid (TSA) and lipid-bound sialic acid (LSA) were determined in the cerebrospinal fluid (CSF) from 63 patients with various neurological diseases. Of these, 27 had brain tumors: 20 had glioma, and 7 pituitary adenoma. TSA levels were significantly increased in the CSF of 18 of the 20 glioma patients (p less than 0.001), while in the adenoma patients were indistinguishable from the controls; with a 90 and 0% test sensitivity respectively. Conversely, the LSA concentrations were significantly elevated, both, in the glioma and pituitary adenoma patients (p less than 0.001), with a 68 and 100% test sensitivity respectively. These preliminary data suggest that measurement of TSA and LSA in the CSF should prove useful for the diagnosis of brain tumors and, perhaps, in the follow-up of patients undergoing treatment for brain tumors.     

Use and limitations of serum total and lipid-bound sialic acid concentrations as markers for colorectal cancer

Concentrations of total serum N-acetyl-neuraminic acid (NANA) by high-performance liquid chromatography (HPLC) and lipid-bound sialic acid (LSA) by resorcinol procedure were evaluated and compared to carcinoembryonic antigen (CEA) as markers for colorectal carcinoma. Elevated concentrations of NANA were found in 32% of patients with nonmalignant disorders, 28% of patients with localized cancer, and 87% of patients with metastatic cancer. All three markers correlated with the extent of metastasis of colorectal carcinoma. Strong correlation was found between NANA and LSA measurements, whereas measurement of the sialic acid markers provide information that can not be derived from the measurement of CEA. NANA and LSA show promise as supplemental markers for staging and monitoring colorectal cancer, but they are neither sensitive nor specific enough for cancer screening.     

Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity

Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH) (galactose and mannose). The changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers. All four parameters were significantly elevated in oral PC patients compared with controls. The levels of PBH and LSA showed significant increase in the oral PC patients compared with the normal tobacco chewers. A significant increase was observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients compared with controls, normal tobacco chewers, and patients with oral PC. Increasing levels of all the biomarkers were found with progression of the malignant disease. Elevations in the levels of TSA and LSA were statistically significant in Stage IV patients compared with Stage III patients. The patients with metastases had higher levels of the biomarkers than the patients with primary OC. However, elevations only in LSA levels were statistically significant. These results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral PC or OC. In addition to their value in early detection, they can also help in staging of the disease.     

唾液酸作为肺癌标志物的ROC分析

用受试者试验特征性曲线（ROC）建立了血清TSA与LSA对肺癌与非癌患者的最佳诊断分界值（Cut－off），TSA为76mg／dl，LSA为23mg／dl，肺癌组TSA与LSA的含量均明显高林非癌组，同时比较了TSA与LSA的诊断灵敏度，特异性，符合率，ROCAUC和信息量。血清唾液酸作为肺癌标志物时，TSA与LSA的ROCAUC无显著性差异（P＞O．05），二者间信息量的u值为0．91，P＞0．05。提示只要选一个最佳cut－off值，单测血清TSA就有可能达到筛选肺癌的目的。     

唾液酸作为肺癌标志物的ROC分析

用受试者试验特征性曲线（ROC）建立了血清TSA与LSA对肺癌与非癌患者的最佳诊断分界值（Cut－off），TSA为76mg／dl，LSA为23mg／dl，肺癌组TSA与LSA的含量均明显高林非癌组，同时比较了TSA与LSA的诊断灵敏度，特异性，符合率，ROCAUC和信息量。血清唾液酸作为肺癌标志物时，TSA与LSA的ROCAUC无显著性差异（P＞O．05），二者间信息量的u值为0．91，P＞0．05。提示只要选一个最佳cut－off值，单测血清TSA就有可能达到筛选肺癌的目的。     

Correlation of total (TSA) and lipid and bound (LSA) sialic acid levels with cytology of cyst or body fluids in cancer patients.

In this preliminary study, aiming at the early diagnosis or the confirmation of neoplastic spreading, the levels of sialic acid (TSA and LSA, total sialic acid and "lipid bound" sialic acid) were measured and correlated with the corresponding cytologic findings in 111 body or cystic fluid samples taken from patients with suspected or confirmed cancer. The samples were classified according to the body fluid origin: peritoneal (35), breast cyst (22), pleural (21), thyroid gland cyst (5), renal cyst (5), ovarian cyst (6), bronchial washing (3), douglasic cavity (3) and various other origins (11). It was found that 32.43% of the samples were TSA positive, 44.14% LSA positive, 20.75% cytologic and 8.49% cytology suspect (positive + suspect = 29.24%). Thus, the combination of a tumor biomarker with the corresponding cytology of the body fluid gives the best possible results, as regards both the confirmation of positive cytology and the detection of possible metastases, as well as the monitoring of the disease after treatment.     

Significance of serum protein and lipid-bound sialic acid as a marker for genitourinary malignancies

A prospective study was done to evaluate the roles of serum N-acetylneuraminic acid (NANA) and the lipid-bound subfraction of sialic acid (LSA) concentrations in the detection and staging of cancer, and the follow-up of treatment in patients with genitourinary malignancies. Multiple determinations were obtained in 177 subjects: 90 normal volunteers, 38 patients with prostate cancer, 20 patients with bladder cancer, 15 patients with renal cell cancer, and 14 patients with benign urologic diseases. The results showed a low incidence of elevated values in patients with early stages of cancer and a high incidence of false-positive values with serum NANA concentrations in patients with benign urologic diseases, especially prostatitis. Serum NANA and LSA concentrations were highly correlated with the stage and grade in patients with advanced urologic cancer, and may be used as markers of tumor activity during follow-up under treatment; currently, however, they are not useful in the screening of patients for urologic cancer. Their usefulness in prostatic cancer is at least comparable to that of acid phosphatase determinations by the enzymatic and radioimmunoassay methods, which were elevated in a smaller percentage of patients with prostate cancer than were the NANA or LSA concentrations.     

Clinical evaluation of four tumor markers in malignant and benign pleural effusions.

Total sialic acid (TSA), lipid-bound sialic acid (LSA), ferritin and carcinoembryonic antigen (CEA) were evaluated in 55 patients with malignant pleural effusions and in 32 patients with benign (exudative) pleural effusions. No significant differences were found in the pleural fluid TSA, LSA and ferritin levels between malignant and benign conditions. CEA levels in malignant effusions were significantly higher than those in benign effusions (43.13 +/- 72.8 ng/ml versus 2.6 +/- 5.56 ng/ml, p less than 0.01). At a cut-off level of 5 ng/ml, 60% of the patients with cancer showed elevated pleural fluid CEA levels. The specificity and diagnostic accuracy of CEA in distinguishing malignant from benign pleural exudates were both very high (91% and 71% respectively). Therefore, of the four markers investigated, only CEA could be a valuable tool in the detection of pleural malignancy.     

Total and lipid-associated serum sialic acid levels in cancer patients with different primary sites and differing degrees of metastatic involvement

Serum total sialic acid (TSA) and lipid-associated sialic acid (LASA) levels have drawn considerable interest because of carbohydrate aberrations in malignant cells. The current investigation determined the TSA, LASA, total protein (TP), and TSA/TP values for 171 cancer patients with various primary sites and differing degrees of metastatic disease, 102 patients with nonmalignant diseases (pathologic controls), and 42 normal individuals. Data analysis indicated significant (p less than 0.01) increases in the mean (+/- SD) TSA and TSA/TP values in the cancer patients (78.1 +/- 19.2 mg/dl and 12.4 +/- 3.8 mg/g, respectively) and in the pathologic controls (76.0 +/- 7.5 mg/dl and 11.6 +/- 2.5 mg/g) when compared to the normal controls (67.3 +/- 7.1 mg/dl and 9.0 +/- 1.1 mg/g), and a significant decrease in the mean TP values in the cancer patients (6.4 +/- 1.1 g/dl) and pathologic controls (6.6 +/- 1.1 g/dl) when compared to normal controls (7.5 +/- 0.5 g/dl). No significant difference was observed between groups in LASA values. Further analysis of the data in patient subgroups based on the tissue involved, specific disease, or severity of the malignancy indicated that the lack of specificity of the markers was due primarily to restricted subgroups and that the sensitivity of TSA and TSA/TP increased as the malignancy became more severe. The results show that TSA/TP was the most useful of the markers tested for detecting malignancies. This marker should prove useful for monitoring malignant disease recurrence and/or progression and for evaluating the effectiveness of various therapeutic approaches.     

Serum osteoprotegerin levels in healthy controls and cancer patients.

PURPOSE: Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor receptor superfamily. In vitro, OPG blocks osteoclastogenesis in a dose-dependent manner. Serum OPG levels were assayed in cancer patients and healthy control subjects using an ELISA. RESULTS: OPG levels in healthy controls were significantly higher in sera (0.17 ng/ml) than in plasma (0.14 ng/ml). OPG levels did not differ by age in either control group. Serum was available from patients with solid tumors (n = 145), hematological malignancies (n = 111), benign hematological disorders (n = 35), and rheumatologic diseases (n = 60). When adjusted for age and sex, there was no significant OPG elevation in the sera of patients with solid tumors compared with controls (0.2 versus 0.18 ng/ml). When analyzed by site of primary malignancy within the solid tumor patient group, serum OPG elevations were observed only in patients with colorectal cancer (0.29 ng/ml; P < 0.0001) and pancreatic cancer (0.35 ng/ml; P < 0.0001). When analyzed by site of metastasis within the solid tumor patient group, significant elevations in serum OPG were observed only in patients with liver metastases (0.29 ng/ml) and soft tissue metastases (0.21 ng/ml) but not in patients with bone or lung metastases. Within the hematological malignancy group, serum levels of OPG were significantly lower in patients with multiple myeloma (0.12 ng/ml) but were elevated in patients with Hodgkin's disease (0.29 ng/ml) and Non-Hodgkin's Lymphoma (0.24 ng/ml; P = 0.048). CONCLUSIONS: Although some patients with malignancy have significant elevations of circulating OPG, these concentrations do not approach the level that would be expected to suppress osteoclast function.     

Serum sialic acid (TSA/LSA) and carcinoembryonic antigen (CEA) levels in cancer patients undergoing radiotherapy.

The main aim of this study was to evaluate the response of total Sialic Acid (TSA) and "Lipid-bound" Sialic Acid (LSA) compared to Carcinoembryonic Antigen (CEA), in 284 patients undergoing radiotherapy. Serial measurements of TSA by the enzymatic method (Boehringer-Mannheim Kit), LSA by the resorcinol-HC1 (Katopodis and Stock) and CEA by EIA (Abbott Kit) were performed in a total of 1017 blood sera. We statistically estimated the four greater groups of cancer patients [bladder (69), lung (58), uterus (31) and breast (29)]. Diagnostic marker sensitivities (% true positives) estimated from the 0-time-values--before initiation of radiotherapy--in relation to the established cut-off levels were in decreasing order: TSA 89.3% (80 mg/dL). LSA 88.8% (20 mg/dL) and CEA 26.75% (5 ng/mL). The overall tumor marker response to treatment, after its completion, estimated as % of patients with final blood serum levels of these markers, was in decreasing order: LSA 85.6%, TSA 81.3%, and CEA 65.8%. These data show that a) the diagnostic sensitivity of Sialic Acid (LSA/TSA) is more than 3 times higher than that of CEA and b) the response of Sialic Acid (LSA/TSA) to treatment is about 15% higher than that of CEA. In conclusion, this study confirms the high diagnostic sensitivity of Sialic Acid as a tumor marker and suggests that, with marginal superiority of Sialic Acid, all three markers are sufficiently responsive to be employed as adjunctive means in monitoring cancer patients underdoing radiotherapy.     

Improved procedure for determination of serum lipid-associated sialic acid: application for early diagnosis of colorectal cancer

We have developed a simple and reliable procedure for determining serum levels of lipid-associated sialic acid (LASA) in crude preparations. This method extracts essentially all gangliosides, excludes glycoprotein-bound sialic acid, and gives LASA values (0.5-1.0 mg/dL) in good agreement with values for isolated serum gangliosides. The procedure was used to determine serum levels of LASA in patients with colorectal cancer, in patients with nonmalignant diseases (pathological control subjects), and in normal control subjects. The results indicated that the percentages of total sialic acid (TSA) comprised by LASA (LASA/TSA X 100) were elevated in patients with the earliest stages of colorectal cancer, compared with percentages in normal control subjects (P less than .001) and pathological control subjects (P less than .01).     

Lipid bound sialic acid in cancer patients

Serum lipid-bound sialic acid (LSA) was measured with a recently described procedure in 108 healthy subjects and in 138 patients with a variety of solid tumors and hematologic malignancies. At the time of serum sampling, 128 patients had active disease and 10 patients had no evidence of disease. LSA was elevated in 104 of 128 (81.2%) patients with active disease, while carcinoembryonic antigen, analyzed in 74, was elevated only in 21 (28.4%) (P less than 0.05). Sensitivity of the serum LSA test ranged from 66% for breast and gastrointestinal cancer to 92% for lung cancer. In patients with lung cancer, ovarian cancer or Hodgkin's disease, LSA was correlated with the extent of disease and it also proved to be useful in following the course of disease. Our preliminary data indicate that this test can be used as a monitor of tumor burden.     

Conventional tumor markers are prognostic indicators in patients with head and neck squamous cell carcinoma

We tested for squamous cell carcinoma-related antigen (SCC), carcinoembryonic antigen (CEA), ferritin, immunosuppressive acid protein (IAP) and sialic acid in the serum from 247 patients with head and neck squamous cell carcinoma prior to therapy. Significant correlations were found between IAP and tumor size, lymph node metastasis, and clinical stage (P<0.0001, P<0.001, and P<0.0001). Also, sialic acid and SCC were also correlated with tumor size, lymph node metastasis, and clinical stage. Moreover IAP, sialic acid and SCC were strongly associated with survival rate (P<0.0001, P = 0.0230 and P = 0.0159). A multivariate Cox proportional hazard model demonstrated that being positive for IAP was an independent predictor for patients with H&NSCC (P = 0.0115). The results indicate that IAP, sialic acid and SCC are useful as prognostic factors.