Human Kallikrein 5: An Interesting Novel Biomarker in Ovarian Cancer Patients that Elicits a Humoral Response

2009 ◽  
Vol 24 (3) ◽  
pp. 211-211
Author(s):  
Elisabetta Bandiera ◽  
Laura Zanotti ◽  
Eliana Bignotti ◽  
Chiara Romani ◽  
Renata Tassi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Immune Complexes ◽  
Tumor Antigens ◽  
Gynecological Cancer ◽  
Sandwich Elisa ◽  
Ovarian Tumors ◽  
Borderline Tumors ◽  
Healthy Women ◽  
Ovarian Masses

Background and aim Epithelial ovarian cancer (EOC) is characterized by few early symptoms, presentation at an advanced stage and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. Recently, not only tumor antigens but also antibodies produced in response to the disease have been considered as biomarkers for early detection of EOC. Kallikrein-related peptidases (KLK) are secreted serine proteases implicated in tumor progression. A recent study has demonstrated that the serum KLK5 (sKLK5) concentration is elevated in patients with EOC, but the existence of a humoral immune response to KLK5 has not been studied. Moreover, the presence of sKLK5 in other ovarian diseases has not been clearly determined. The aim of this study was to examine the serological existence of anti-KLK5 antibodies, bound to KLK5 into circulating immune complexes (KLK5-lgM and KLK5-lgG ICs) or free antibodies (IgM and IgG), in healthy women and in patients with benign ovarian masses, borderline tumors and EOC. In the same patients we also assessed the levels of sKLK5. Materials and methods Serum samples were obtained from 50 healthy women, 50 patients with benign ovarian masses, 1 7 patients with borderline ovarian tumors, and 50 patients with EOC, before any surgical or chemotherapeutic treatment. Patients with a past or concomitant history of malignancy were excluded from the study. KLK5-lgM and KLK5-lgG ICs were detected with a sandwich ELISA using a polyclonal anti-KLK5 antibody (R&D Systems, Minneapolis, MN, USA) in capture and an anti-hlgM-HRP antibody (Sigma Aldrich Inc, St Louis, MO, USA) or anti-hlgG-HRP antibody (Sigma) in detection. Free anti-KLK5 IgM and IgG were detected with an indirect ELISA using recombinant human kallikrein 5 (R&D) in coating and anti-hlgM-HRP or anti-hlgG-HRP antibodies in detection. Finally, sKLK5 was detected with a sandwich ELISA, using a polyclonal anti-KLK5 antibody in capture and a biotinylated poyclonal anti-hK5 antibody (R&D) in detection. Results Elevated levels of KLK5-lgM and KLK5-lgG ICs were detected in 11% of patients with borderline tumors and 8% of patients with EOC, whereas elevated levels of free anti-KLK5 IgM and IgG were found in 1 7% of patients with borderline tumors and 8% of patients with EOC, resulting in a 100% specificity both in healthy women and patients with benign ovarian disease. Patients with EOC showed higher levels of sKLK5, whereas the protein was almost undetectable in women with other ovarian tumors (Kruskal-Wallis test: p<0.001). In particular, at 95% specificity in healthy controls, 52% of patients with EOC showed high sKLK5 levels. Interestingly, both the immune complexes and the free antibodies were elevated in patients with undetectable sKLK5 levels and borderline tumors with intraepithelial carcinoma. Conclusion Our results showed that sKLK5 is a potential new biomarker to be used in combination with other biomarkers for EOC detection. Moreover, the combination of sKLK5 and antibodies reactive to KLK5 might improve the sensitivity in EOC detection since these antibodies may be found in patients without detectable sKLK5 levels. In conclusion, the identification of an immune response that generally precedes the presence of high levels of circulating antigens may represent a novel useful tool for early EOC detection.

Borderline Ovarian Tumors

2021 ◽  
pp. 223-239
Author(s):  
George Pados ◽  
Dimitrios Zouzoulas
Keyword(s):  
Ovarian Cancer ◽  
Gold Standard ◽  
Early Stage ◽  
Ovarian Tumors ◽  
Microscopic Appearance ◽  
Borderline Tumors ◽  
Non Invasive ◽  
Borderline Ovarian Tumors ◽  
Specific Subgroup ◽  
Serous Tumors

Borderline ovarian tumors (BOTs) are a specific subgroup of ovarian tumors and are characterized by cell proliferation and nuclear atypia without invasion or stromal invasion. They are usually more present in younger people than the invasive ovarian cancer and are diagnosed at an early stage and thus have a better prognosis. Histologically, borderline tumors are divided into serous (50%), mucosal (46%), and mixed (4%). The serous tumors are bilateral in 30% of the cases and are accompanied by infiltrations outside the ovary in 35% of the cases. These infiltrations may be non-invasive or invasive depending on their microscopic appearance and may affect treatment. Surgery is the approach of choice, and laparoscopic surgery, with the undeniable advantages it offers today, is the “gold standard.” All the surgical steps required to properly treat borderline tumors, at both diagnostic and therapeutic levels, can be safely and successfully be applied laparoscopically. Manipulations during surgery should be limited, and biopsies for rapid biopsy should be done within an endoscopic bag.

Evaluation of Proteomics-Identified CCL18 and CXCL1 as Circulating Tumor Markers for Differential Diagnosis between Ovarian Carcinomas and Benign Pelvic Masses

2011 ◽  
Vol 26 (4) ◽  
pp. 262-273 ◽  
Author(s):  
Qi Wang ◽  
Danrong Li ◽  
Wei Zhang ◽  
Bujian Tang ◽  
Qingdi Quentin Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Differential Diagnosis ◽  
Tumor Markers ◽  
Laser Desorption ◽  
Ca 125 ◽  
Laser Desorption Ionization ◽  
Desorption Ionization ◽  
Healthy Women ◽  
Pelvic Masses ◽  
Ovarian Masses

A lack of sensitive and specific tumor markers for early diagnosis and treatment is a major cause for the high mortality rate of ovarian cancer. The purpose of this study was to identify potential proteomics-based biomarkers useful for the differential diagnosis between ovarian cancer and benign pelvic masses. Serum samples from 41 patients with ovarian cancer, 32 patients with benign pelvic masses, and 41 healthy female blood donors were examined, and proteomic profiling of the samples was assessed by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy (MS). A confirmatory study was also conducted with serum specimens from 58 patients with ovarian carcinoma, 37 patients with benign pelvic masses, and 48 healthy women. A classification tree was established using Biomarker Pattern Software. Six differentially expressed proteins (APP, CA 125, CCL18, CXCL1, IL-8, and ITIH4) were separated by high-performance liquid chromatography and identified by matrix-assisted laser desorption/ionization (MALDI)-MS/MS and database searches. Two of the proteins overexpressed in ovarian cancer patients, chemokine CC2 motif ligand 18 (CCL18) and chemokine CXC motif ligand 1 (CXCL1), were automatically selected in a multivariate predictive model. These two protein biomarkers were then validated and evaluated by enzyme-linked immunosorbent assay (ELISA) in 535 serum specimens (130 ovarian cancer, 64 benign ovarian masses, 36 lung cancer, 60 gastric cancer, 55 nasopharyngeal carcinoma, 48 hepatocellular carcinoma, and 142 healthy women). The combined use of CCL18 and CXCL1 as biomarkers for ovarian cancer had a sensitivity of 92% and a specificity of 97%. The multivariate ELISA analysis of the two putative markers in combination with CA 125 resulted in a sensitivity of 99% for healthy women and 94% for benign pelvic masses, and a specificity of 92% for both groups; these values were significantly higher than those obtained with CA 125 alone (P<0.05). We conclude that serum CCL18 and CXCL1 are potentially useful as novel circulating tumor markers for the differential diagnosis between ovarian cancer and benign ovarian masses.

scholarly journals Biomarker-based early detection of epithelial ovarian cancer based on a five-protein signature in patient’s plasma – a prospective trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Hasenburg ◽  
D. Eichkorn ◽  
F. Vosshagen ◽  
E. Obermayr ◽  
A. Geroldinger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Regression Model ◽  
Plasma Levels ◽  
Prospective Trial ◽  
Predictive Marker ◽  
Diagnostic Value ◽  
Ovarian Tumors ◽  
Link Type ◽  
Logistical Regression ◽  
Ovarian Masses

Abstract Background Trial on five plasma biomarkers (CA125, HE4, OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors. Methods In this unicentric prospective trial preoperative blood samples of 43 women with ovarian masses determined for ovarian surgery were analyzed. 25 patients had pathologically confirmed benign, 18 malignant ovarian tumors. Blood plasma was analyzed for CA125, HE4, OPN, leptin, prolactin and MIF by multiplex immunoassay analysis. Each single protein and a logistical regression model including all the listed proteins were tested as preoperative predictive marker for suspect ovarian masses. Results Plasma CA125 was confirmed as a highly accurate tumor marker in ovarian cancer. HE4, OPN, leptin and prolactin plasma levels differed significantly between benign and malignant ovarian masses. With a logistical regression model a formula including CA125, HE4, OPN, leptin and prolactin was developed to predict malignant ovarian tumors. With a discriminatory AUC of 0.96 it showed to be a highly sensitive and specific diagnostic test for a malignant ovarian tumor. Conclusions The calculated formula with the combination of CA125, HE4, OPN, leptin and prolactin plasma levels surpasses each single marker in its diagnostic value to discriminate between benign and malignant ovarian tumors. The formula, applied to our patient population was highly accurate but should be validated in a larger cohort. Trial registration Clinical Trials.gov under NCT01763125, registered Jan. 8, 2013.

scholarly journals The diagnosis and pathological value of combined detection of HE4 and CA125 for patients with ovarian cancer

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Li-e Zheng ◽  
Jun-ying Qu ◽  
Fei He
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Tumors ◽  
Clinical Staging ◽  
Ca 125 ◽  
Cancer Antigen 125 ◽  
Healthy Women ◽  
Cancer Group ◽  
Clinical Biomarker ◽  
Benign Ovarian Tumors ◽  
The Relationship

AbstractObjectiveTo evaluate the value of individual and combined measurement of human epididymis protein 4 (HE4) and cancer antigen 125 (CA-125) in the diagnosis of ovarian cancer.MethodsA clinical case-control study was performed in which the levels of serum HE4 and CA-125 of subjects with malignant, borderline, benign ovarian tumors and healthy women were measured before surgery. An immunohistochemistry method was used to measure the expression of HE4 in different tissues. Statistical analysis was performed to determine the relationship between the level of HE4 and the pathologic type as well as the stage of the ovarian tumors.ResultsThe level of HE4 in the serum was significantly elevated in the malignant ovarian cancer group compared with other groups. Women with benign ovarian tumors and non-neoplastic lesions, and healthy women were designated as references. When the level of HE4 in the serum was 58.66 pmol/L, the sensitivity and specificity of HE4 in diagnosing malignant ovarian tumors was 82.35% and 96.03%, respectively. The level of HE4 was negatively correlated with the differentiation extent of the tumors whereas positively correlated to the clinical staging. In the groups of malignant and borderline tumors, the levels of HE4 were higher than the other groups. The expression of HE4 was significant higher in the serous types of ovarian tumors than that of the mucous types (P<0.05). The level of HE4 in the serum and tissues were positively correlated with each other.ConclusionHE4 can be used as a novel clinical biomarker for predicting malignant ovarian tumors and its expression was closely related with the clinical pathological features of malignant ovarian tumors.

scholarly journals A Clinicopathological Study of Malignant Ovarian Tumors in India

2014 ◽  
Vol 2 (1) ◽  
pp. 9-11 ◽  
Author(s):  
Renu Rajvanshi ◽  
Rekha Rani ◽  
Mohita Agrawal
Keyword(s):  
Ovarian Cancer ◽  
Early Diagnosis ◽  
Cause Of Death ◽  
South Asian ◽  
Gynecological Cancer ◽  
Ovarian Tumors ◽  
Morbidity And Mortality ◽  
Diagnosis And Treatment ◽  
Surgical Staging ◽  
Clinicopathological Study

ABSTRACT Ovarian cancer is the leading cause of death from gynecological cancer. Material and method Surgical staging of all cases of ovarian cancer were done. Result and conclusion Of the 50 cases of ovarian tumors operated 44% were malignant.duration of symptoms was 1 month or less in majority of patients. Bilaterality was found in 27.3% of tumors. The most common histotype was serous. Early diagnosis and treatment can reduce the morbidity and mortality if the clinician keeps this in mind. How to cite this article Garg R, Singh S, Rani R, Agrawal M, Rajvanshi R. A Clinicopathological Study of Malignant Ovarian Tumors in India. J South Asian Feder Menopause Soc 2014;2(1):9-11.

scholarly journals Proteome Profiling Uncovers an Autoimmune Response Signature That Reflects Ovarian Cancer Pathogenesis

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 485
Author(s):  
Makoto Kobayashi ◽  
Hiroyuki Katayama ◽  
Ehsan Irajizad ◽  
Jody V. Vykoukal ◽  
Johannes F. Fahrmann ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Tumor Antigens ◽  
Tumor Development ◽  
Autoimmune Response ◽  
Driver Genes ◽  
Cancer Driver ◽  
Humoral Immune ◽  
Cancer Pathogenesis ◽  
Cancer Driver Genes

Harnessing the immune response to tumor antigens in the form of autoantibodies, which occurs early during tumor development, has relevance to the detection of cancer at early stages. We conducted an initial screen of antigens associated with an autoantibody response in serous ovarian cancer using recombinant protein arrays. The top 25 recombinants that exhibited increased reactivity with cases compared to controls revealed TP53 and MYC, which are ovarian cancer driver genes, as major network nodes. A mass spectrometry based independent analysis of circulating immunoglobulin (Ig)-bound proteins in ovarian cancer and of ovarian cancer cell surface MHC-II bound peptides also revealed a TP53–MYC related network of antigens. Our findings support the occurrence of a humoral immune response to antigens linked to ovarian cancer driver genes that may have utility for early detection applications.

PARTICULARITIES OF THE IMMUNE RESPONSE IN PERSONS PROFESSIONNALLY EXPOSED TO BERYLLIUM

2016 ◽  
pp. 26-30
Author(s):  
K. I. Stosman ◽  
L. V. Lukovnikova
Keyword(s):  
Immune Response ◽  
Immune Complexes ◽  
Immunoglobulin E ◽  
Circulating Immune Complexes ◽  
Professional Contact ◽  
Beryllium Compounds

An examination was performed of 50 employees at an enterprise where they were in professional contact with beryllium. In most workers, it was detected an increase of interleukine-8, interferon- , growing level of immunoglobulin E and circulating immune complexes. It was shown that the contact with beryllium compounds leads to the interferon- level growth only in women. In men, alterations are identified in the direction of increased concentrations of common immunoglobulin E and circulating immune complexes.

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