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1. EP2727935 - Serum markers associated with early and other stages of breast cancer

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[ EN ]
Claims

1. A cancer peptide motif from a protein selected from the group consisting of mucin, vacuolar protein sorting associated protein 36, protein kinase C-binding protein 1, is-let cell autoantigen 69, nuclear receptor coactivator 5, and dermcidin.
  2. The cancer peptide motif of claim 1, having an amino acid sequence selected from the group consisting of SEQ ID NOs: 89, 6, 76, 12, 46, 23, 96, 37, 9, 10, 27, 28, 29, and 40.
  3. The cancer peptide motif of claim 2, wherein the amino acid sequence is SEQ ID NO: 89, 6, 76 or 12.
  4. The cancer peptide motif of claim 3, wherein the amino acid sequence is SEQ ID NO: 89.
  5. An isolated antibody that binds specifically to the cancer peptide motif of any one of claims 1-4.
  6. A method of detecting a low copy number cancer peptide motif of any one of claims 1-4 in a biological sample, comprising

(a) obtaining the biological sample comprising a plurality of serum albumin complexes;

(b) separating the serum albumin complexes on a membrane by a two-dimensional membrane electrophoresis;

(c) digesting at least one separated serum albumin complex on the membrane with a protease; and

(d) detecting the cancer peptide motif in the digested complex.


  7. A method of identifying a disease-specific marker, comprising:

(a) obtaining a biological sample comprising a plurality of serum albumin complexes from a reference subject, wherein the plurality of serum albumin complexes from the reference subject comprise the cancer peptide motif of any one of claims 1-4;

(b) obtaining a biological sample comprising a plurality of serum albumin com-plexes from a diseased subject, wherein the plurality of serum albumin complexes from the disease subject comprise the cancer peptide motif;

(c) separating the serum albumin complexes in step (a) by a two-dimensional membrane electrophoresis to generate a reference separation profile;

(d) separating the serum albumin complexes in step (b) by a two-dimensional membrane electrophoresis to generate a disease separation profile;

(e) comparing the reference separation profile with the disease separation profile to determine whether there is a difference in the number, distribution or both number and distribution of the separated serum albumin complexes between the reference separation profile and the disease separation profile, wherein the difference represents a disease-specific marker.


  8. A method of diagnosing a disease in a test subject, comprising

(a) obtaining a biological sample comprising a plurality of serum albumin com-plexes from the test subject, wherein the plurality of serum albumin complexes from the test subject comprise the cancer peptide motif of any one of claims 1-4;

(b) separating the serum albumin complexes by a two-dimensional membrane electrophoresis to generate a test separation profile;

(c) providing a reference separation profile representing the disease; and

(d) comparing the test separation profile with the reference separation profile to determine whether there is a substantial similarity between the test separation profile and the reference separation profile, wherein the substantial similarity indicates that the test subject has the disease.


  9. A method of staging cancer in a test subject, comprising

(a) obtaining a biological sample comprising a plurality of serum albumin complexes from the test subject, wherein the plurality of serum albumin complexes from the test subject comprise the cancer peptide motif of any one of claims 1-4;

(b) separating the serum albumin complexes by a two-dimensional membrane electrophoresis to generate a test separation profile;

(c) providing a plurality of stage-specific reference separation profiles representing the cancer; and

(d) comparing the test separation profile with the stage-specific reference separation profiles to determine whether there is a substantial similarity between the test separation profile and one of the stage-specific reference separation profiles, wherein the substantial similarity indicates that the test subject has the specific cancer stage represented by the one of the stage-specific reference separation profiles.


  10. The method of any one of claims 6-9, wherein at least one of the serum albumin complexes is a breast cancer complex selected from the group consisting of Stage 0 Complexes, Stage I Complexes, Stage II Complexes, Stage III Complexes and Stage IV Complexes.
  11. The method of claim 7 or 8, wherein the disease is selected from the group consisting of cancer, a neurological disease, an autoimmune disease, and a heart disease.
  12. The method of claim 9 or 11, wherein the cancer is selected from the group consist-ing of adenocarcinoma of rectum, bladder cancer, breast cancer, colon cancer, en-dometrial carcinoma, esophagus squamous cell carcinoma, glioma, hepatocellular carcinoma, infiltrating ductal breast carcinoma, larynx cancer, lung squamous cell carcinoma, melanoma, mucinous cystadenocarcinoma of ovary, pancreatic cancer, prostate cancer, renal cell carcinoma, small bowel malignant stromal tumor, and stomach adenocarcinoma.
  13. The method of claim 11, wherein the neurological disease is selected from the group consisting of Alzheimer's disease, multiple sclerosis, Parkinson's disease, and migraine headaches.