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Fulltext Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma

Stepien M, Lopez-Nogueroles M, Lahoz A, Kühn T, Perlemuter G, Voican C, et al.

Int J Cancer, 2022 Apr 15;150(8):1255-1268.
PMID: 34843121 DOI: 10.1002/ijc.33885

Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.

Matched MeSH terms: Biomarkers, Tumor/blood*
Human mammaglobin in breast cancer: a brief review of its clinical utility

Al Joudi FS

Indian J Med Res, 2014 May;139(5):675-85.
PMID: 25027076

Human mammaglobin is a member of the uteroglobin proteins family that has recently been tested as a specific marker for breast cancer. While low levels may be seen in normal breast tissue, expression is increased dramatically in breast cancer and is correlated with higher grade. Detection in blood and body fluids is also correlated with cancer metastasis, and its levels with prognosis. This promises to be a useful screen for early detection of breast cancer, especially in high risk individuals. Mammoglobin has also been used for immunotherapeutic targeting of breast cancer cells. However, there are some controversies regarding its diagnostic efficacy and prognostic value, which warrant further study.

Matched MeSH terms: Biomarkers, Tumor/blood
Comparison of Serum Fucose Levels in Leukoplakia and Oral Cancer Patients

Rai NP, Anekar J, Shivaraja Shankara YM, Divakar DD, Al Kheraif AA, Ramakrishnaiah R, et al.

Asian Pac J Cancer Prev, 2015;16(17):7497-500.
PMID: 26625751

BACKGROUND: Tumor markers, designated as a broad group of substances produced by malignancies, could be in the form of biochemical substances, immunological substances, cell surface changes and genetic alterations. Cancer, a disorder of cellular behavior is characterized by alteration of serum glycoproteins. L-fucose, a hexose, which is the terminal sugar in most of the plasma glycoproteins, may be useful as a tumor marker for the detection, monitoring and prognostic assessment of malignancies. The aim of the study was to ascertain the role of serum fucose as a biomarker for early detection of oral cancer and to compare serum fucose levels in healthy controls, leukoplakia and oral cancer patients.
MATERIALS AND METHODS: The study included 60 (100.0%) subjects, who were grouped as 20 (33.3%) control subjects, 20 (33.3%) squamous cell carcinoma patients and 20 (33.3%) leukoplakia patients. Fucose estimation was done using UV-visible spectrophotometry based on the method as adopted by Winzler using cysteine reagent. The results were analyzed statistically using ANOVA with Bonferroni post hoc tests.
RESULTS: Results showed a high significance in serum fucose in oral squamous cell carcinoma (OSCC) and leukoplakia subjects compared to normal controls. There was a gradual increase in the values noted from control to leukoplakia and to squamous cell carcinoma.
CONCLUSIONS: Estimation of serum fucose may be a reliable marker and can be used as an effective diagnostic biomarker in oral squamous cell carcinoma patients.

Matched MeSH terms: Biomarkers, Tumor/blood*
Fulltext Distinguishing benign from malignant pelvic mass utilizing an algorithm with HE4, menopausal status, and ultrasound findings

Wilailak S, Chan KK, Chen CA, Nam JH, Ochiai K, Aw TC, et al.

J Gynecol Oncol, 2015 Jan;26(1):46-53.
PMID: 25310857 DOI: 10.3802/jgo.2015.26.1.46

The purpose of this study was to develop a risk prediction score for distinguishing benign ovarian mass from malignant tumors using CA-125, human epididymis protein 4 (HE4), ultrasound findings, and menopausal status. The risk prediction score was compared to the risk of malignancy index and risk of ovarian malignancy algorithm (ROMA).

Matched MeSH terms: Biomarkers, Tumor/blood*
Gelsolin and ceruloplasmin as potential predictive biomarkers for cervical cancer by 2D-DIGE proteomics analysis

Lokamani I, Looi ML, Md Ali SA, Mohd Dali AZ, Ahmad Annuar MA, Jamal R

Pathol Oncol Res, 2014 Jan;20(1):119-29.
PMID: 23925487 DOI: 10.1007/s12253-013-9670-9

This study aimed to identify candidate proteins which may serve as potential biological markers for cervical cancer using 2D-DIGE. Serum samples of controls, patients with cervical intraepithelial neoplasia grade 3 (CIN 3), squamous cell carcinoma of early (SCC I and II) and late (SCC III and IV) stage were subjected to 2D-DIGE. Differentially expressed spots were identified by tandem mass spectrometry. Validation of candidate proteins in serum and tissue samples were then performed by ELISA and immunohistochemistry (IHC) analysis respectively. A total of 20 differentially expressed proteins were identified. These proteins were found to play key roles in the apoptosis pathway, complement system, various types of transportation such as hormones, fatty acids, lipid, vitamin E and drug transportation, coagulation cascade, regulation of iron and immunologic response. Based on their functional relevancy to the progression of various cancers, 4 proteins namely the complement factor H, CD5-like antigen, gelsolin and ceruloplasmin were chosen for further validation using ELISA. Biological network analysis showed that ceruloplasmin and gelsolin are closely interacted with the oncogene NF-κb. These two proteins were further validated using the IHC. Gelsolin and ceruloplasmin may serve as potential predictive biomarkers for the progression of high grade lesions.

Matched MeSH terms: Biomarkers, Tumor/blood*
Nutritional status among pediatric cancer patients: a comparison between hematological malignancies and solid tumors

Tah PC, Nik Shanita S, Poh BK

J Spec Pediatr Nurs, 2012 Oct;17(4):301-11.
PMID: 23009042 DOI: 10.1111/j.1744-6155.2012.00341.x

This study aimed to compare the nutritional status of pediatric patients with hematological malignancies and solid tumors.

Matched MeSH terms: Biomarkers, Tumor/blood
Can the acute-phase reactant proteins be used as cancer biomarkers?

Pang WW, Abdul-Rahman PS, Wan-Ibrahim WI, Hashim OH

Int. J. Biol. Markers, 2010 Jan-Mar;25(1):1-11.
PMID: 20155712

The association between the acute-phase reactant proteins (APRPs) and cancer has long been established. There have been numerous reports correlating altered levels of various APRPs with different types of cancers. However, researchers are often quick to dismiss the use of these APRPs as potential biomarkers for the diagnosis and monitoring of cancer because alterations in APRP concentrations are observed in a wide range of diseases. Recent progress in proteomics studies which profiled the serum proteins of cancer patients and those of normal individuals indicated that the altered APRP expressions were different for distinct types, subtypes, and even stages of cancer. Interestingly, these data are in agreement with those observed earlier using immunochemical and biochemical assays. In view of this compelling association of different patterns of APRPs with various types of cancers and in an apparent shift of paradigm, we present in this review some indications that APRP fingerprinting may be used as complementary cancer biomarkers.

Matched MeSH terms: Biomarkers, Tumor/blood*
Fulltext Hydatidiform mole and post-evacuation regression patterns of serum beta human chorionic gonadotrophin

Kamariah K, Satgunasingam N, Nasri NM, Ng KY

Med J Malaysia, 1993 Mar;48(1):40-5.
PMID: 7688063

Eighty-nine patients who had hydatidiform moles evacuated at the General Hospital, Kuala Lumpur, were followed with serum beta hCG determinations from October 1988 to June 1991. A regression curve for serum beta hCG, as measured by RIA, was derived from the results of 47 of the patients who demonstrated spontaneous regression of serum beta hCG titres. All 47 patients had normal serum titres at 135 days after evacuation. The mean time taken to reach normal level was 82.6 days, while the range was 39 to 135 days (5 to 19 weeks).

Matched MeSH terms: Biomarkers, Tumor/blood*
Are plasma insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) useful markers of prostate cancer?

Lopez JB, Sahabudin RM, Chin LP

Int. J. Biol. Markers, 2004 Apr-Jun;19(2):164-7.
PMID: 15255551

Increased concentrations of insulin-like growth factor I (IGF-I) and decreased insulin-like growth factor binding protein 3 (IGFBP-3) in serum have been proposed as markers of prostate cancer (CaP). The evidence for this, however, is contradictory. We assayed serum for IGF-I, IGFBP-3 and prostate-specific antigen (PSA) in patients with CaP and benign prostatic hyperplasia (BPH) and in healthy controls (HC). The mean +/- SD concentration of IGF-I in CaP (98.3 +/- 39.3 ng/mL; n = 15) was lower than in BPH (119 +/- 31.1 ng/mL; n=24) and HC (119 +/- 36.1 ng/mL; n=46), but the differences between the three groups were not statistically significant (p > 0.05). The mean IGFBP-3 concentrations in CaP (2691 +/- 1105 ng/mL; n = 16; p = 0.029) and BPH (2618 +/- 816 ng/mL; n = 26; p = 0.006) patients were significantly lower than that of the HC (3119 +/- 618 ng/mL; n=59), but the difference between the two groups of patients was not significant (p > 0.05). PSA concentrations in CaP (median = 80.8 ng/mL; n = 25) were significantly higher than those in BPH (median = 8.6 ng/mL; n = 39) (p < 0.001). Ninety-six percent of CaP and 72% of BPH patients had PSA concentrations >4.0 ng/mL; the proportions of patients with concentrations exceeding 20 ng/mL were 76% and 10%, respectively. We conclude that IGF-I and IGFBP-3 are inferior to PSA for CaP detection.

Matched MeSH terms: Biomarkers, Tumor/blood*
Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis

Yap NY, Yap FN, Perumal K, Rajandram R

Biomarkers, 2019 Sep;24(6):607-614.
PMID: 31215811 DOI: 10.1080/1354750X.2019.1634763

Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels. Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC. Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan. Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels. Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.

Matched MeSH terms: Biomarkers, Tumor/blood
Ratiometric Detection of microRNA Using Hybridization Chain Reaction and Fluorogenic Silver Nanoclusters

Wong ZW, Ng JF, New SY

Chem Asian J, 2021 Dec 13;16(24):4081-4086.
PMID: 34668337 DOI: 10.1002/asia.202101145

miRNA (miR)-155 is a potential biomarker for breast cancers. We aimed at developing a nanosensor for miR-155 detection by integrating hybridization chain reaction (HCR) and silver nanoclusters (AgNCs). HCR serves as an enzyme-free and isothermal amplification method, whereas AgNCs provide a built-in fluorogenic detection probe that could simplify the downstream analysis. The two components were integrated by adding a nucleation sequence of AgNCs to the hairpin of HCR. The working principle was based on the influence of microenvironment towards the hosted AgNCs, whereby unfolding of hairpin upon HCR has manipulated the distance between the hosted AgNCs and cytosine-rich toehold region of hairpin. As such, the dominant emission of AgNCs changed from red to yellow in the absence and presence of miR-155, enabling a ratiometric measurement of miR with high sensitivity. The limit of detection (LOD) of our HCR-AgNCs nanosensor is 1.13 fM in buffered solution. We have also tested the assay in diluted serum samples, with comparable LOD of 1.58 fM obtained. This shows the great promise of our HCR-AgNCs nanosensor for clinical application.

Matched MeSH terms: Biomarkers, Tumor/blood*
Fulltext A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study

Chajès V, Assi N, Biessy C, Ferrari P, Rinaldi S, Slimani N, et al.

Ann Oncol, 2017 Nov 01;28(11):2836-2842.
PMID: 28950350 DOI: 10.1093/annonc/mdx482

BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.
MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.
RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.
CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Matched MeSH terms: Biomarkers, Tumor/blood*
Fulltext Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case-control sets from EPIC

Schmidt JA, Fensom GK, Rinaldi S, Scalbert A, Appleby PN, Achaintre D, et al.

Int J Cancer, 2020 Feb 01;146(3):720-730.
PMID: 30951192 DOI: 10.1002/ijc.32314

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.

Matched MeSH terms: Biomarkers, Tumor/blood*
Fulltext Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Stepien M, Jenab M, Freisling H, Becker NP, Czuban M, Tjønneland A, et al.

Carcinogenesis, 2017 Jul 01;38(7):699-707.
PMID: 28575311 DOI: 10.1093/carcin/bgx051

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression.

Matched MeSH terms: Biomarkers, Tumor/blood*
Fulltext Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Duell EJ, Lujan-Barroso L, Sala N, Deitz McElyea S, Overvad K, Tjonneland A, et al.

Int J Cancer, 2017 Sep 01;141(5):905-915.
PMID: 28542740 DOI: 10.1002/ijc.30790

Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155 and -212) overall, and for four miRs (-10a, -10b, -21-5p and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (p-value = 0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-5p).

Matched MeSH terms: Biomarkers, Tumor/blood
Fulltext Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Dossus L, Franceschi S, Biessy C, Navionis AS, Travis RC, Weiderpass E, et al.

Int J Cancer, 2018 Apr 01;142(7):1332-1342.
PMID: 29168186 DOI: 10.1002/ijc.31172

Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 = 0.69, 95% CI: 0.49-0.98, Ptrend = 0.04) but not among men (ORT3vs.T1 = 1.36, 95% CI: 0.67-2.76, Ptrend = 0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 = 1.59, 95% CI: 1.13-2.25, Ptrend = 0.01) but not in men (ORT3vs.T1 = 1.78, 95% CI: 0.80-3.98, Ptrend = 0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.

Matched MeSH terms: Biomarkers, Tumor/blood*
Fulltext Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Stepien M, Keski-Rahkonen P, Kiss A, Robinot N, Duarte-Salles T, Murphy N, et al.

Int J Cancer, 2021 Feb 01;148(3):609-625.
PMID: 32734650 DOI: 10.1002/ijc.33236

Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

Matched MeSH terms: Biomarkers, Tumor/blood*
Pattern of tissue expression of CA-125 and HE4 in primary epithelial ovarian tumours and correlation with serum CA-125 levels

Devan SM, Pailoor J, Sthaneshwar P, Narayanan V

Asian Pac J Cancer Prev, 2013;14(8):4545-8.
PMID: 24083699

The objective of this study is to assess tissue expression of CA-125 and HE4 protein in primary benign and malignant epithelial tumours of the ovary and correlate with serum CA-125 levels. A total of 100 formalin-fixed, paraffin embedded sections of ovarian tumours which included serous adenoma (11), mucinous adenoma (42), serous carcinoma (20), mucinous carcinoma (12) and endometrioid carcinoma (15), histologically diagnosed between 1st January 2004 to 31st December 2012 at the University Malaya Medical Centre, were stained for HE4 (rabbit polyclonal antibody, Abcam, UK) and CA-125 (mouse monoclonal antibody clone: OC125, Cell Marque Corporation, Rocklin, California, USA). Pre-operative serum CA-125 levels were obtained from the laboratory information system. Immunoscore (I score) for HE4 and CA-125 was given based on the intensity of staining and percentage of positive tumour cells and considered significant when it was >50 (intensity of staining multiplied by percentage of positive tumour cells). Serum CA-125 levels were compared with the I score of HE4 and CA-125 in tissues. We noted that the CA-125 levels in serum and tissues were significantly raised in malignant compared to benign ovarian tumours (p value<0.05). Tissue expression of HE4 protein was also significantly raised in malignant tumours compared to benign tumours (p value<0.05). We conclude that HE4 can be a useful tissue immunomarker in addition to CA-125.

Matched MeSH terms: Biomarkers, Tumor/blood
Identification of potential complementary serum biomarkers to differentiate prostate cancer from benign prostatic hyperplasia using gel- and lectin-based proteomics analyses

Jayapalan JJ, Ng KL, Razack AH, Hashim OH

Electrophoresis, 2012 Jul;33(12):1855-62.
PMID: 22740474 DOI: 10.1002/elps.201100608

Diagnosis of prostate cancer (PCa) is currently much reliant on the invasive and time-consuming transrectal ultrasound-guided biopsy of the prostate gland, particularly in light of the inefficient use of prostate-specific antigen as its biomarker. In the present study, we have profiled the sera of patients with PCa and benign prostatic hyperplasia (BPH) using the gel- and lectin-based proteomics methods and demonstrated the significant differential expression of apolipoprotein AII, complement C3 beta chain fragment, inter-alpha-trypsin inhibitor heavy chain 4 fragment, transthyretin, alpha-1-antitrypsin, and high molecular weight kininogen (light chain) between the two groups of patients' samples. Our data are suggestive of the potential use of the serum proteins as complementary biomarkers to effectively discriminate PCa from BPH, although this requires further extensive validation on clinically representative populations.

Matched MeSH terms: Biomarkers, Tumor/blood*
Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women

Looi LM, Cheah PL, Ng MH, Yip CH, Mun KS, Rahman NA

Asian Pac J Cancer Prev, 2010;11(3):713-6.
PMID: 21039041

A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.

Matched MeSH terms: Biomarkers, Tumor/blood

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