Humoral immune response to p53 correlates with clinical course in colorectal cancer patients during adjuvant chemotherapy

Lechpammer, Mirna; Lukač, Josip; Lechpammer, Stanislav; Kovačević, Dujo; Loda, Massimo; Kusić, Zvonko

doi:10.1007/s00384-003-0553-5

Cited by 46 publications

(31 citation statements)

References 23 publications

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“…33 There is a strong correlation between accumulation of p53 in primary tumor cells and presence of serum p53-specific antibodies in patients with different tumor types. 34 Multiple studies have focused on the evaluation of autoantibodies to p53 as a diagnostic tool due to reports suggesting that the antibody responses to p53 can occur early in the course of a cancer and predict undetected malignancy or premalignancy. One of the earliest reports described the evolution of the p53 antibody response in patients at high risk of developing lung cancer, heavy smokers.…”

Section: Methods To Identify Serum Autoantibodies As Potential Diagnomentioning

confidence: 99%

Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer

2008

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Over the past decade, it has been demonstrated that cancer is immunogenic, and multiple tumor antigens have been identified in cancer patients. It is now possible to potentially harness the immune response elicited by cancer growth as a potential diagnostic tool. Humoral immunity, or the development of autoantibodies against tumor-associated proteins, may be used as a marker for cancer exposure. Unlike circulating proteins that are shed by bulky tumors, serum autoantibodies are detectable even when antigen expression is minimal. This paper will review the methods used for tumor antigen discovery and overview what is known about autoantibodies targeting common cancer antigens with a focus on breast cancer. Data will be presented modeling the use of tumor antigen associated autoantibodies as a breast cancer diagnostic. The endogenous humoral immune response present in cancer patients may allow the identification of individuals exposed to the malignant transformation of somatic cells.

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Section: Methods To Identify Serum Autoantibodies As Potential Diagnomentioning

confidence: 99%

Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer

2008

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“…In this regard, several tumor-associated antigens have been reported for their humoral response in various human cancers. Autoantibodies against p53, p62, ING1 (tumor suppressor), NY-BR-62, and NY-BR-85 with low frequency range have been reported in breast cancer (4,7,8). Because tumorassociated antigens are self-proteins and are not much immunogenic, further efforts are being made to identify immunogenic tumor antigens.…”

Section: Introductionmentioning

confidence: 99%

Sperm-Associated Antigen 9, a Novel Biomarker for Early Detection of Breast Cancer

Kanojia

Garg

Gupta³

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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To date, there have been no tumor biomarkers validated and incorporated into oncologic practice for the early diagnosis of breast cancer. Recently, we showed that sperm-associated antigen 9 (SPAG9), a member of cancer testis (CT) antigen family, is associated with ovarian carcinomas. In the present study, we investigated SPAG9 expression and humoral immune response in breast cancer. We further evaluated the diagnostic potential of autoantibodies to SPAG9 protein in various stages, grades, and histotypes of breast cancer. We analyzed the association of SPAG9 immunoreactivity score (IRS) with predicted risk of breast cancer recurrence over 10 years. Our reverse transcription-PCR and immunohistochemical analyses revealed SPAG9 expression in 88% breast cancer specimens independent of tumor stages and grades. Further, the humoral immune response against SPAG9 was detected in 80% breast cancer patients with SPAG9-expressing tumors. The linear regression modeling predicted a direct relationship between presence of lymphovascular invasion and high SPAG9 IRS, whereas the univariate and multivariate logistic regression models predicted a strong association of SPAG9 IRS with tumor grade. Further, our data indicated a significant higher trend of SPAG9 IRS with the predicted high risk of breast cancer recurrence. The present investigation reports for the first time SPAG9 expression and humoral immune response in early stages and low-grade breast cancer. Although our data indicated that autoantibodies against SPAG9 represent a promising approach for the development of biomarker, further large-scale validation studies are required to establish its potential use in early diagnosis and monitoring of breast cancer recurrence. (Cancer Epidemiol Biomarkers Prev 2009;18(2):630 -9)

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“…Thirty percent of patients with ductal carcinoma in situ in which the proto-oncogene HER-2/neu was overexpressed had serum antibodies specific to this protein (8,9). In addition, antibodies to p53 have been reported in patients with early-stage ovarian or colorectal cancers (10,11). Changes in the level of gene expression in cancer (4,8,12,13) and aberrant expression of tissue-restricted gene products in cancer (14,15) are factors in the development of a humoral immune response in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Markers of Ovarian Cancer by High-Throughput Antigen Cloning and Detection on Arrays

et al. 2006

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A noninvasive screening test would significantly facilitate early detection of epithelial ovarian cancer. This study used a combination of high-throughput selection and arraybased serologic detection of many antigens indicative of the presence of cancer, thereby using the immune system as a biosensor. This high-throughput selection involved biopanning of an ovarian cancer phage display library using serum immunoglobulins from an ovarian cancer patient as bait. Protein macroarrays containing 480 of these selected antigen clones revealed 65 clones that interacted with immunoglobulins in sera from 32 ovarian cancer patients but not with sera from 25 healthy women or 14 patients having other benign or malignant gynecologic diseases. Sequence analysis data of these 65 clones revealed 62 different antigens. Among the markers, we identified some known antigens, including RCAS1, signal recognition protein-19, AHNAK-related sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic initiation factor 5A, and casein kinase II, as well as many previously uncharacterized antigenic gene products. Using these 65 antigens on protein microarrays, we trained neural networks on two-color fluorescent detection of serum IgG binding and found an average sensitivity and specificity of 55% and 98%, respectively. In addition, the top 6 of the most specific clones resulted in an average sensitivity and specificity of 32% and 94%, respectively. This global approach to antigenic profiling, epitomics, has applications to cancer and autoimmune diseases for diagnostic and therapeutic studies. Further work with larger panels of antigens should provide a comprehensive set of markers with sufficient sensitivity and specificity suitable for clinical testing in high-risk populations. (Cancer Res 2006; 66(2): 1181-90)

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Humoral immune response to p53 correlates with clinical course in colorectal cancer patients during adjuvant chemotherapy

Cited by 46 publications

References 23 publications

Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer

Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer

Sperm-Associated Antigen 9, a Novel Biomarker for Early Detection of Breast Cancer

Diagnostic Markers of Ovarian Cancer by High-Throughput Antigen Cloning and Detection on Arrays

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