Ideal Tumor Marker Research Articles

Simultaneous Quantification of Serum Lipids and Their Association with Type 2 Diabetes Mellitus-Positive Hepatocellular Cancer.

Type 2 diabetes mellitus (T2DM) has been recognized as one of the most important and independent risk factors for hepatocellular cancer (HCC). However, there is still a lack of ideal tumor markers for HCC detection in the T2DM population. Serum lipids have been revealed as potential tumor markers for HCC. In this study, our objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect several lipids including 8,15-dihydroxy-5,9,11,13-eicosatetraenoic acid (8,15-DiHETE), hexadecanedioic acid (HDA), 15-keto-13,14-dihydroprostaglandin A2 (DHK-PGA2), ricinoleic acid (RCL), octadecanedioic acid (OA) and 16-hydroxy hexadecanoic acid (16OHHA) in serum and explore their diagnostic potential for T2DM-positive [T2DM(+)] HCC. A robust LC-MS/MS method was established for the measurement of 8,15-DiHETE, HDA, DHK-PGA2, RCL, OA, and 16OHHA. The methodology validation was conducted, and the results suggested the reliability of this LC-MS/MS method for targeted lipids. Several serum lipids, including 8,15-DiHETE, HDA, DHK-PGA2, and OA were increased in T2DM(+) HCC patients. A biomarker signature that incorporated HDA, DHK-PGA2, and AFP was established and showed good diagnostic potential for T2DM(+) HCC, and the area under the ROC curve (AUC) was 0.87 for diagnosing T2DM(+) HCC from T2DM individuals. Additionally, the biomarker signature diagnosed small-size (AUC = 0.88) and early-stage (AUC = 0.79) tumors with high efficacy. Moreover, the biomarker signature could differentiate T2DM(+) HCC from other T2DM(+) tumors, including pancreatic, gastric and colorectal cancer (AUC = 0.88) as well. In conclusion, our study develops a novel tool for early diagnosis of T2DM(+) HCC in T2DM patients.

Construction of 2DE Patterns of Plasma Proteins: Aspect of Potential Tumor Markers.

The use of tumor markers aids in the early detection of cancer recurrence and prognosis. There is a hope that they might also be useful in screening tests for the early detection of cancer. Here, the question of finding ideal tumor markers, which should be sensitive, specific, and reliable, is an acute issue. Human plasma is one of the most popular samples as it is commonly collected in the clinic and provides noninvasive, rapid analysis for any type of disease including cancer. Many efforts have been applied in searching for “ideal” tumor markers, digging very deep into plasma proteomes. The situation in this area can be improved in two ways—by attempting to find an ideal single tumor marker or by generating panels of different markers. In both cases, proteomics certainly plays a major role. There is a line of evidence that the most abundant, so-called “classical plasma proteins”, may be used to generate a tumor biomarker profile. To be comprehensive these profiles should have information not only about protein levels but also proteoform distribution for each protein. Initially, the profile of these proteins in norm should be generated. In our work, we collected bibliographic information about the connection of cancers with levels of “classical plasma proteins”. Additionally, we presented the proteoform profiles (2DE patterns) of these proteins in norm generated by two-dimensional electrophoresis with mass spectrometry and immunodetection. As a next step, similar profiles representing protein perturbations in plasma produced in the case of different cancers will be generated. Additionally, based on this information, different test systems can be developed.

Tumormarkers in clinical practice

Tumor markers are assuming a growing role in all aspects of cancer care, starting from screening to follow-up after treatment, and their judicious application in clinical practice needs a thorough understanding of the basics of pathophysiology, techniques of identification or testing, reasons for out-of-range levels of tumor markers, as well as the knowledge of evidence of their role in any given malignancy. These are, at the most, just an adjunct to diagnosis, and establishing a diagnosis on the basis of tumor markers alone (especially a single result) is fraught with associated pitfalls because of the problem of non-specificity. An ideal tumor marker does not exist. Detection can be done either in tissue or in body fluids like ascitic or pleural fluid or serum. Clinical uses can be broadly classified into 4 groups: screening and early detection, diagnostic confirmation, prognosis and prediction of therapeutic response and monitoring disease and recurrence. In addition to variable sensitivity and specificity, the prevalence of a particular malignancy may be a major determinant in the application of a particular test as a screening tool. Serum levels, in certain situations, can be used in staging, prognostication or prediction of response to therapy. Monitoring disease is, perhaps, the most common clinical use of serum tumor markers. Rising trend in serum levels may detect recurrence of disease well before any clinical or radiological evidence of disease is apparent ("biochemical recurrence"). Sampling should ideally be repeated after 5-6 half-lives of the marker in question (or the marker with the longest half-life if multiple markers are being considered); but if found elevated, the next sampling after 2-4 weeks, for additional evidence, may be justified.

Faecal haemoglobin concentration in adenoma, before and after polypectomy, approaches the ideal tumour marker.

BackgroundPolypectomy may be performed at colonoscopy and then subsequent surveillance undertaken. It is thought that faecal haemoglobin concentration (f-Hb), estimated by quantitative faecal immunochemical tests (FIT), might be a useful tumour marker.MethodsConsecutive patients enrolled in colonoscopy surveillance were approached at two hospitals. A specimen for FIT was provided before colonoscopy and, ideally after 3 weeks, a second FIT sample from those who had polypectomy. A single FIT system (OC-Sensor io, Eiken Chemical Co., Ltd) was used to generate f-Hb.Results1103 Patients were invited; 643 returned a FIT device (uptake: 58.3%). Four patients had known inflammatory bowel disease (IBD) and were excluded, leaving 639 (57.9%) with an age range of 25–90 years (median 64 years), 54.6% male. Of 593 patients who had a f-Hb result and completed colonoscopy, advanced neoplasia was found in 41 (6.9%); four colorectal cancer (CRC): 0.7% and 37 advanced adenoma (AA): 6.3%, and a further 127 (21.4%) had non-advanced adenoma (NAA). The median f-Hb was significantly greater in AA as compared to NAA; 6.0 versus 1.0 μg Hb/g faeces, p < 0.0001.134/164 (81.7%) of invited patients returned a second FIT device: 28 were patients with AA in whom median pre-polypectomy f-Hb was 19.2, falling to 3.5 μg Hb/g faeces post-polypectomy, p = 0.01, and 106 with NAA had median pre-polypectomy f-Hb 0.8 compared to 1.0 μg Hb/g faeces post-polypectomy, p = 0.96.ConclusionsQuantitative FIT could provide a good tumour marker in post-polypectomy surveillance, reduce colonoscopy requirements and minimise potential risk to patients.

Peptide Nucleic Acid-Functionalized Nanochannel Biosensor for the Highly Sensitive Detection of Tumor Exosomal MicroRNA.

Compared with free miRNAs in blood, miRNAs in exosomes have higher abundance and stability. Therefore, miRNAs in exosomes can be regarded as an ideal tumor marker for early cancer diagnosis. Here, a peptide nucleic acid (PNA)-functionalized nanochannel biosensor for the ultrasensitive and specific detection of tumor exosomal miRNAs is proposed. After PNA was covalently bound to the inner surface of the nanochannels, the detection of tumor exosomal miRNAs was achieved by the charge changes on the surface of nanochannels before and after hybridization (PNA-miRNA). Due to the neutral characteristics of PNA, the efficiency of PNA-miRNA hybridization was improved by significantly reducing the background signal. This biosensor could not only specifically distinguish target miRNA-10b from single-base mismatched miRNA but also achieve a detection limit as low as 75 aM. Moreover, the biosensor was further used to detect exosomal miRNA-10b derived from pancreatic cancer cells and normal pancreatic cells. The results indicate that this biosensor could effectively distinguish pancreatic cancer tumor-derived exosomes from the normal control group, and the detection results show good consistency with those of the quantitative reverse-transcription polymerase chain reaction method. In addition, the biosensor was used to detect exosomal miRNA-10b in clinical plasma samples, and it was found that the content of exosomal miRNA-10b in cancer patients was generally higher than that of healthy individuals, proving that the method is expected to be applied for the early diagnosis of cancer.

Prostate-Specific antigen: An overview and its current status in the diagnosis of prostate cancer

Prostate-Specific Antigen (PSA), which has high organ specificity and poor cancer specificity, has been widely utilized for the diagnosis and treatment of prostate cancer; though it is not an ideal tumor marker. Its extensive usage in screening programs has resulted in a large number of unwanted biopsies, over-diagnosis and over-treatment of indolent cancers as well. Hence, various PSA derivatives and PSA-based tests have evolved to improve the accuracy of prostate cancer diagnosis. This article provides an overview of PSA and PSA-based biomarkers and their current role in the screening and diagnosis of prostate cancer.

Tumor Markers in Endometrial Cancer

The purpose of this review is to update readers on recent findings about serum tumor markers in clinical settings of endometrial cancer. The latest research on this topic discussed risk factors of pelvic lymph node metastasis and levels of two serum tumor markers (human epididymis protein 4 and cancer antigen 125; HE4, CA-125) preoperatively in the patients with endometrial cancer. This study showed that higher preoperative laboratory results of human epididymis protein 4 and CA-125 are independent risk factors for pelvic lymph node metastasis in endometrial cancer patients. Based on this research, lymphadenectomy is not recommended if none of independent risk factors is present. Prevention of unnecessary lymph node resection and complications associated with lymphadenectomy for low-risk patients is made possible. The authors suggested more effective predictors of lymph node metastasis should be investigated to provide theoretical support for deciding lymphadenectomy and guide the individualized endometrial cancer care. Evaluation of the endometrium with invasive procedures is the only method to determine endometrial cancer. Tumor markers are used for the initial diagnosis of the disease, determining risk stratification and prognosis. For now, there is no ideal marker identified for endometrial cancer. With recent progresses in molecular biology, the mechanisms underlying endometrial cancer have been understood gradually. Thus, several investigations have been carried out to find new candidate biomarkers in the last decade. Human epididymis protein 4 is shown to have a good performance for clinical use as a prognostic factor in endometrial cancer. However, further large prospective randomized trials are needed to confirm the prognostic role of it. The use of ideal tumor marker for endometrial cancer will permit earlier detection of disease and better prognostic assessment and improve the patient’s outcome.

8-Isoprostane: A salivary oxidative stress biomarker for oral submucous fibrosis and oral squamous cell carcinoma.

Background:8-isoprostane is one of the stable oxidative stress marker formed by the lipid peroxidation of arachidonic acid. It is present in detectable quantities in all biological fluids. Elevation of 8-Isoprostane has been reported in various neurological, cardiological disorders, and periodontal diseases.Aim:The present study was conducted to estimate and compare the level of 8-isoprostane in plasma and saliva in patients with oral squamous cell carcinoma (OSCC), oral submucous fibrosis (OSMF), and in controls. The study also aimed to find out if 8-isoprostane can be used as an effective oxidative stress marker in evaluating the disease progression in OSCC.Materials and Methods:Plasma and salivary samples were taken from 10 cases each of clinically diagnosed OSMF, clinically and hisotpathologically diagnosed cases of OSCC and controls. The samples were subjected to 8-Isoprostane ELISA procedure and analyzed. Statistical analysis was performed using the SPSS software.Results:The levels of 8-isoprostane in plasma showed an average increase from normal to OSMF to OSCC but was not statistically significant. The variations in the level of salivary 8-isoprostane were found to be statistically significant (P = 0.037) suggesting that there is a gradual increase in levels of isoprostane from controls to OSMF to OSCC.Conclusion:The results showed that the concentration of isoprostane in saliva showed a progressive and steady increase from control through OSMF to OSCC indicating that saliva could be used as an effective diagnostic tool in estimating tumor markers. Large scale studies correlating with other potentially malignant oral disorders are required to ascertain the role of 8-Isoprostane as an ideal tumor marker.

Evaluation of platelet distribution width as novel biomarker in gall bladder cancer.

INTRODUCTION:Gall bladder cancer (GBC) tends to present in advanced stages, therefore, early diagnosis of GBC is necessary. There is no ideal single tumor marker available presently for the diagnosis and prognosis of GBC. Platelet distribution width (PDW) is an early marker for activated platelets and has been used in a variety of tumors to assess prognosis. This study was designed to evaluate the utility of PDW in identifying GBC patients and its association with tumor markers, staging and resectability of GBC.MATERIALS AND METHODS:This cross sectional study was done on 100 patients of GBC and 100 age- and sex- matched healthy controls. PDW was evaluated and compared between GBC and healthy controls. Receiver-operating characteristics was plotted to determine optimal cut-off for identifying GBC patients and to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PDW. Correlation between serum tumor markers (carbohydrate antigen 19-9, carcinoembryonic antigen, and carbohydrate antigen 125) and PDW were evaluated. Association of PDW with hyperbilirubinemia, staging and resectability of GBC was also studied.RESULTS:A significantly higher PDW with a median of 18.1 was observed in GBC as compared to healthy controls with median value of 13. PDW was found to have a very high sensitivity (90%), specificity (95%), PPV (94%) and NPV (90%) in identifying GBC at cut-off of 16 with area under the curve (AUC) of 0.97. An increase of PDW was observed with increasing stage and unresectable GBC. However, it was not statistically significant. Significant positive correlation was observed between PDW and all three serum tumor markers and good positive correlation with r = 0.61 was observed with CA 19-9.CONCLUSION:PDW was associated with GBC and may be considered as a cost- effective marker in adjunct to other investigations for the diagnosis of GBC.

Downregulated Expression of hsa_circ_0005556 in Gastric Cancer and Its Clinical Significance.

Background Gastric cancer (GC) has a poor prognosis due to the lack of ideal tumor markers. Circular RNAs (circRNAs) are a novel type of noncoding RNA related to the occurrence of GC. Among our research, we investigated the role of hsa_circ_0005556 in GC. Materials and Methods The expression of hsa_circ_0005556 of 100 paired GC tissues and adjacent normal tissues was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0005556. The correlation between the expression of hsa_circ_0005556 and corresponding clinicopathological characteristic was explored. Results hsa_circ_0005556 was significantly downregulated in GC tissues contrasted with adjacent normal tissues (n = 100, p < 0.001). The areas under the ROC curve (AUC) of hsa_circ_0005556 were up to 0.773, while 64% sensitivity and 82% specificity, respectively. Moreover, its expression levels were significantly associated with differentiation (p = 0.001), TNM stage (p = 0.013), and lymphatic metastasis (p = 0.039). GC patients of high hsa_circ_0005556 levels had a longer overall survival (OS) than those of the low group (p = 0.047). Conclusion hsa_circ_0005556 is a potential biomarker for GC, which may guide judgment of the indication of endoscopic treatment for early gastric cancer (EGC).

Low Expression of hsa_circ_0018069 in Human Bladder Cancer and Its Clinical Significance.

Abnormal expression of noncoding RNA molecules such as circRNA plays an important role in the development of malignant tumors. circRNAs are stable in structure and can be useful as ideal tumor markers. Advanced bladder cancer has poor treatment options and prognosis. Thus, we examined circRNAs to further understand the pathogenesis and development of bladder cancer and to identify molecular markers for the early diagnosis of bladder carcinoma. We found that hsa_circ_0018069 was differentially expressed in our RNA sequencing data. We used qRT-PCR to detect its expression in T24 and Biu-87 cell lines and in 41 paired samples of bladder cancer and adjacent normal tissue and analyzed the correlation between expression of hsa_circ_0018069 and the clinical characteristics of patients with bladder cancer. We then performed a bioinformatics analysis to reveal the mechanism of hsa_circ_0018069 in tumorigenesis of bladder cancer. The expression of hsa_circ_0018069 was significantly reduced in T24 and Biu-87 cells and was also significantly downregulated in bladder cancer tissues. Decreased expression of hsa_circ_0018069 was related to the grade stage (P=0.024), T stage (P=0.027), and muscular invasion depth (P=0.022) of bladder cancer. Bioinformatics analysis showed that hsa_circ_0018069 was coexpressed with protein-coding mRNAs that participate in cytoskeletal protein binding and cell-substrate junction assembly and play an anticancer role through focal adhesion and calcium signaling pathways. ceRNA analysis showed that hsa_circ_0018069 functions in ErbB, Ras, FoxO, and the focal adhesion signaling pathway by harboring miR-23c, miR-34a-5p, miR-181b-5p, miR-454-3p, and miR-3666. hsa_circ_0018069 may thus play an important role in the occurrence and progression of bladder cancer and serve as a valuable biomarker for the early diagnosis of this disease.

Prognostic nutritional index as a predictor of survival in resectable gastric cancer patients with normal preoperative serum carcinoembryonic antigen levels: a propensity score matching analysis

BackgroundAn ideal tumor marker should be capable of being detected at any stage of the disease. However, gastric cancer patients do not always have elevated serum carcinoembryonic antigen (CEA) levels, even in advanced cases. Recently, several studies have investigated the associations between preoperative PNI and postoperative long-term outcomes. In this study, we focused on the significance of the prognostic nutritional index (PNI) as a potential predictor of survival in resectable gastric cancer patients with normal preoperative serum CEA levels.MethodsWe retrospectively conducted cohort study to evaluate the PNI as a predictor of survival in 368 resectable gastric cancer patients who underwent potentially curative gastrectomy at our institute between January 2010 and December 2016. We selected 218 patients by propensity score matching to reduce biases due to the different distributions of co-variables among the comparable groups.ResultsIn the multivariate analysis, pStage (hazard ratio [HR]: 14.003, 95% confidence interval [CI]: 5.033–44.487; p < 0.001), PNI (HR: 2.794, 95% CI: 1.352–6.039; p < 0.001) were identified as independent prognostic factors of CSS in 218 propensity matched gastric cancer patients. The Kaplan-Meier analysis demonstrated that low PNI patients had a significantly poorer cancer specific survival (CSS) than high PNI patients (p = 0.008).Among 166 propensity matched gastric cancer patients with normal preoperative serum CEA levels, multivariate analysis demonstrated that pStage (HR: 7.803, 95% CI: 3.015–24.041; p < 0.001) and PNI (HR: 3.078, 95% CI: 1.232–8.707; p = 0.016) were identified as independent prognostic factors of CSS. And Kaplan-Meier analysis demonstrated that low PNI had a significantly poorer CSS than high PNI value (p = 0.011).ConclusionsThis study demonstrates that a low preoperative PNI value is a potential independent risk factor for poorer CSS in patients with gastric cancer, even in those with normal serum CEA levels.

Involvement of erbB4 and tumor marker genes in renal carcinoma regulatory network.

BackgroundRenal carcinoma is a common urologic tumor, and there is no ideal tumor marker for clinical diagnosis except for imaging diagnosis. This study aims to screen the serum tumor markers closely related with the benign and malignant of renal carcinoma out and chart out the regulatory network that involves renal carcinoma-related genes.MethodsBased on 96 pathologically diagnosed renal cancer patients, factors strongly linked to renal carcinoma character were selected using Fisher discriminant analysis. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to manipulate function annotation of erbB4 and the selected genes and pathway analysis.ResultsFour essential tumor markers CYFRA21-1, CA125, VHL and HIF-1β were successfully screened out. Using GO and KEGG databases, the regulatory network of renal cancer cell escaping apoptosis was charted out on the basis of erbB4 signaling pathway.ConclusionSerum tumor marker genes play a certain part in the genesis and development of renal carcinoma. We preliminarily illustrated the molecular mechanism of these markers to predict tumor, laying a foundation for further exploration in renal carcinoma.

Analysis of intra-tumor heterogeneity in breast cancer precision medicine

As a breakthrough of precision medicine, intra-tumor heterogeneity is a research hotspot and is correlated to tumorigenesis, metastasis and resistance to therapies. In breast cancer, evidence of intra-tumor heterogeneity has been documented by numerous studies and it is the main obstacle to find ideal tumor markers and personalized medicine. Further analysis including the feature and generation mechanism of intra-tumor heterogeneity and the methods to assessment intra-tumor heterogeneity in the clinic are the key to cancer precision medicine. Key words: Breast neoplasms; Intra-tumor heterogeneity; Precision medicine

Circulating microRNAs - a new horizon in molecular diagnosis of breast cancer.

The potential use of microRNAs (miRNAs) as ideal tumor markers has been the focus of recent research. Our hypothesis was that circulating miRNAs are differentially expressed in pretherapeutic sera of breast cancer patients compared to controls. Using real-time quantitative polymerase chain reaction (qPCR) analysis, levels of 5 candidate miRNAs (miR10b, miR34a, miR155, miR195 and miR16) were quantified in sera of breast cancer patients and control individuals. Levels of preoperative sera showed significant upregulation of 3.36 fold rise in miR10b (p<0.001), a 2.07 fold rise in miR155 (p =0.005) and remarkable over expression of 11.9 fold rise in miR195 (p<0.001) of cases than controls. There was significant down regulation of miR34a (0.032, p<0.001). The comparison with the clinicopathological data of the breast cancer patients revealed significant high serum level of miR155 (p =0.004) and miR195 (p =0.002) in patients with lymph node metastasis and higher levels of miR10b (p =0.001) and miR155 (p <0.001) with distant metastasis (M1) than without metastasis (M0), in addition to significant decrease in miR34a (p <0.001) level in M1 than M0 cases. These findings suggest that systemic circulating miRNAs have potential use as novel biomarkers for breast cancer.

Advances in tumor markers of ovarian cancer for early diagnosis.

Ovarian cancer often occurs in perimenopausal women. The mortality of ovarian cancer is in the first place among gynecological cancers because of no obvious early symptoms and the lack of effective diagnostic approach. Gene chips, proteomics, immunohistochemistry and other methods have become hot topics for early diagnosis of ovarian cancer. However, due to the variety of pathology and not clear enough of mechanism and etiology, there is still no ideal tumor markers with both high specific and sensitivity, which can be applied into clinical early diagnosis for ovarian cancer. Therefore, a new systematic method with high sensitivity and specificity for early diagnosis of ovarian cancer and new tumor markers need to be identified. We should make an examination of ovarian cancer in the early period in the crowd for early diagnosis and early treatment to further improve life quality of patients. This paper reviewed the recent advancements of tumor markers for early diagnosis of ovarian cancer.

History of the development of tumor markers of the digestive tract cancers

Tumor markers are gene products which signal the occurrence of tumors in different organs as well as their response to surgery and chemotherapy. The discovery of tumor markers occurred after the demonstration of tumor-specific transplantation antigens in chemically or virally induced tumors in syngenic rodents. The history of currently used tumor markers began in the 1940s, the first discovered being alpha-fetoprotein in 1956, followed by that of carcinoembryonic antigen in 1965. Since then the range of tumor markers has widened continously. Their chemical structure and genetics is now well known. Some may play part in tumor growth and development of metastases. The potential uses of tumor markers are general or high risk population screening, adjunct in diagnosis of cancer, preoperative indicator of tumor burden, indicator of therapeutic success, evidence of postoperative recurrences and use in tumor localization. However, there is no ideal tumor marker fulfilling all the criteria. Isotope-labeled anti-carcinoembryonic antigen antibodies and small molecular E-selectin inhibitors could play a role in the molecular radio- and chemotherapy of colon and pancreatic carcinomas.

Serum Carcinoembryonic Antigen for Recurrence in Colorectal Cancer Patients

See Article on Page 156-160 Carcinoembryonic antigen (CEA) is secreted by most colorectal cancers, and the CEA level reflects the burden of the tumor present. An elevated preoperative CEA level is a poor prognostic factor for colorectal cancer [1], and the prognosis is better in those patients whose elevated preoperative CEA level is normalized postoperatively. Although an elevated postoperative CEA level is not specific for recurrent colorectal cancer, a rising CEA level on serial examinations and a new solid mass on imaging studies are diagnostic of metastatic disease. The role of CEA in patients following definitive management of colorectal cancer has been evaluated, and the American Society of Clinical Oncology recommended that postoperative serum CEA tests be performed every 3 months in patients with stage II or III disease for up to 3 years after diagnosis [2]. Postoperative serum CEA surveillance was more useful when patients had high preoperative serum CEA levels [3]. When the elevated postoperative serum CEA in stage III (71.9%) was higher than that in stage II colorectal cancer patients (41.8%), the incidence of recurrence was low [4]. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) has an additional role in patients with isolated elevated CEA levels or positive contrast enhanced CT findings without accompanying CEA elevation [5]. Although the CEA is not an ideal tumor marker, the preoperative and the postoperative CEA levels are useful and cost effective for determining a prognosis and for predicting recurrence in colorectal cancer patients.

Squamous cell carcinoma antigen in cervical cancer and beyond

See accompanying articles by Kawaguchi, Shimura and colleagues on pages 313 and 321. Serum tumor markers can have several roles in many aspects of cancer management including early detection or diagnostic confirmation of cancers, predicting prognosis and/or response of specific treatment, and disease monitoring after primary treatment. Because the most of tumor markers have showed variable sensitivity and specificity in various conditions of specific cancers, there has been no ideal tumor marker in current clinical practice in oncology and squamous cell carcinoma antigen (SCC-Ag) in squamous cell carcinoma of cervix (SCC) is not exceptional. Since SCC-Ag, which can be produced through squamous formation of the uterine cervix and increased during the neoplastic transformation of the cervical squamous epithelium, was discovered in 1997 [1,2], many researches have been performed to investigate the role of serum SCC-Ag in SCC. However the clinical implementation of serum SCC-Ag is still controversial. Serum SCC-Ag levels are elevated in 28%-88% of patients with SCC [3]. In early stage of SCC, higher levels of serum SCC-Ag is associated with the pathological risk factors for recurrence such as lymph node metastasis, deep stromal tumor invasion, lymph-vascular space invasion, and larger size of primary tumor in cervix. For example, the positive predictive value for lymph node metastases at >2, >4, and >8.6 ng/mL SCC-Ag is 51.4%, 70.0%, and 100% but the level of SCC-Ag itself was not an independent risk factor for recurrence [4]. On the contrary SCC-Ag level before treatment was reported to be independent risk factors for disease free survival and/or overall survival at multivariate analysis in other studies [5,6]. In a cohort study of 337 patients with IB1-IIA who were surgically treated, it was suggested that serum SCC-Ag level before surgery allows more refined preoperative estimation of the likelihood for adjuvant radiotherapy than pathological risk factors for recurrence representing clinical relevance of serum SCC-Ag in early stage SCC [7]. In locally advanced SCC, pre- and postradiotherapy serum SCC-Ag levels showed the prognostic significance. Hong et al. reported that pretreatment SCC-Ag levels higher than 10 ng/mL are an independent predictor for poor prognosis and persistently elevated SCC-Ag level at 2-3 months after radiotherapy had a significantly higher incidence of treatment failure in their large cohort [8]. In a Japanese study, the SCC-Ag level cut-off point for three-year overall survival rates, calculated using a receiver operating characteristic curve, was 1.15 ng/mL with the sensitivity of 80.0% and specificity of 74.0% [9]. In a retrospective study of 788 patients with SCC, clinical significance as a prognostic marker for progression free and/or overall survival was higher in locally advanced SCC than in early stage SCC [10]. Increasing serum SCC-Ag can precede the clinical diagnosis of relapse in 46%-92% of cases, with a median lead time ranging from 2 to 8 months [3]. However, there is still no strong evidence that the earlier intervention due to early detection of relapse is associated with better survival in recurrent SCC. In a previous study, serum SCC-Ag analysis results in earlier recurrence detection in a small proportion (14%) of patients but did not contribute to better survival [11]. On the other hand, another study reported that salvage treatment with radiotherapy or surgery resulted in improved survival compared with chemotherapy or palliative care in patients with serum SCC-Ag levels of less than <14.0 ng/mL at the time of recurrence [12]. With the limitation of serum SCC-Ag as an ideal biomarker for SCC, other biomarkers such as CYFRA 21-1, immunosuppressive acidic protein, and vascular endothelial growth factor in patients' serum have been investigated but the results were modest or are still investigating [13]. And more recently there have been developments in the use of molecular imaging technology in oncological applications and the use of magnetic resonance imaging or positron emission tomography with or without combination of biomarkers in the management of cervical cancer [14]. In conclusion, serum SCC-Ag is a commonly used and may be the most promising biomarkers in patients with SCC until now. However, clinical relevance of serum SCC-Ag in SCC is still on debate and there should be more researches investigating the clinical application of SCC-Ag and developing new biomarkers in SCC in the future.

Assessing the clinical significance of tumor markers in common neoplasms

The term tumor markers include a spectrum of molecules and substances with widely divergent characteristics whose presence in the significant amount can be related to the malignant disease. An ideal tumor marker should have high specificity and sensitivity, which would allow its use in early diagnosis and prognosis of malignant disease, as well as in prediction of therapeutic response and follow-up of the patients. Numerous biochemical entities have emerged as potentially valuable tumor markers so far, but only few markers showed to be of considerable clinical reliability and have been accepted into standard clinical practice. Recent development of genomics and proteomics has enabled the examination of many new potential tumor markers. Scientific studies on discovery, development, and application of tumor markers have been proceeding quite rapidly providing great opportunities for improving the management of cancer patients. This review is focusing on the clinical usefulness of various tumor markers already in clinical practice as well as certain potential markers, giving a brief description of their prognostic and predictive significance in most common malignancies.