Cancer
The invention relates to biomarkers, and to novel biological markers for diagnosing cancer. In particular, the invention relates to the use of these compounds as diagnostic and prognostic markers in assays for detecting cancer, such as oesophagogastric cancer, and corresponding methods of detection. The invention also relates to methods of determining the efficacy of treating these diseases with a therapeutic agent. The assays are qualitative and/or quantitative, and are adaptable to large-scale screening and clinical trials.
1 . A method of treating an individual suffering from oesophagogastric cancer, said method comprising the steps of:
a) detecting the level of at least one signature compound in a bodily sample from a test subject using gas chromatography, mass spectrometry, and/or GCMS, wherein the bodily sample is a breath sample from the test subject, wherein the at least one signature compound is elected from group (i) consisting of methyl 2,3,5,6-tetra-O-methyl-α-D-galactofuranoside; 1-tetradecanol; N-butyl-benzenesulfonamide; hexadecanoic acid; tetradec-5-yl ester 3,5,5-trimethyl-hexanoic acid; tetradecyl ester undec-10-ynoic acid; 1-dotriacontanol; 1-chloro-tetradecane; 4-methyloctan-1-ol; carbon monoxide; nickel; 2-ethyl-cyclohexylamine; 3-ethyl-1-octene; ethyl lactate; tetramethyl succinimide; 6-methyl-2-heptanone; (E)-ethen-2-d-ol; 4-anilino-4-keto-2-phenyl-butyric acid; diisobutyl (oxybis(ethane-2,1-diyl)) dicarbonate; nickel tetracarbonyl; (E)-2-ethylene-4-methylene-5-hexenal; 3-methyl-1-butyne; (R)-5-methyl-2-(1-methylethylidene)-cyclohexanone; α-propyl-benzeneethanol; 4-methyl-1-pentene; 1,3,3-trimethyl-2-oxabicyclo[2.2.2]oct-5-ene; 2,2′-(ethene-1,2-diylbis(sulfanediyl))diethanol; 3-methyl-thiophene; tert-butyl alcohol; and 2-methoxysuccinonitrile, compared to the reference, in the bodily sample from the test subject, or group (ii) consisting of 4-hydroximino-2,2,6,6-tetramethyl-1-piperidinyl ester 4-amino-benzoic acid; 4,4-dimethyl-octane; benzyl 3-deuterio-α-diazopropionate; and 1-methylethyl ester formic acid; and
b) treating the test subject with a therapeutic agent and/or radiotherapy, if there is an increase in the level of the at least one signature compound selected from group (i) or a decrease in the level of the at least one signature compound selected from group (ii) in the bodily sample from the test subject, compared to a reference, wherein the reference level is the level of the at least one signature compound in an individual, or the average level for a group of individuals, wherein the individual or group of individuals do not suffer from oesophagogastric cancer, wherein the treatment reduces or delays progression of cancer and/or treats cancer.
2 . A method according to claim 1 , wherein the at least one signature compound is selected from the group consisting of methyl 2,3,5,6-tetra-O-methyl-α-D-galactofuranoside; 4-hydroximino-2,2,6,6-tetramethyl-1-piperidinyl ester 4-amino-benzoic acid; 1-tetradecanol; N-butyl-benzenesulfonamide; hexadecanoic acid; tetradec-5-yl ester 3,5,5-trimethyl-hexanoic acid; 4,4-dimethyl-octane; tetradecyl ester undec-10-ynoic acid; 1-dotriacontanol; benzyl 3-deuterio-α-diazopropionate; 1-methylethyl ester formic acid; 1-chloro-tetradecane; 4-methyloctan-1-ol; carbon monoxide; nickel; and 2-ethyl-cyclohexylamine.
3 . A method according to claim 2 , wherein the at least one signature compound is selected from the group consisting of methyl 2,3,5,6-tetra-O-methyl-α-D-galactofuranoside; 4-hydroximino-2,2,6,6-tetramethyl-1-piperidinyl ester 4-amino-benzoic acid; 1-tetradecanol; N-butyl-benzenesulfonamide; hexadecanoic acid; tetradec-5-yl ester 3,5,5-trimethyl-hexanoic acid; 4,4-dimethyl-octane; tetradecyl ester undec-10-ynoic acid; 1-dotriacontanol; and benzyl 3-deuterio-α-diazopropionate.
4 . A method according to claim 3 , wherein the at least one signature compound is selected from the group consisting of methyl 2,3,5,6-tetra-O-methyl-α-D-galactofuranoside; 4-hydroximino-2,2,6,6-tetramethyl-1-piperidinyl ester 4-amino-benzoic acid; 1-tetradecanol; N-butyl-benzenesulfonamide; and hexadecanoic acid.
5 . A method according to claim 1 , wherein the at least one signature compound is selected from the group consisting of 3-ethyl-1-octene; ethyl lactate; tetramethyl succinimide; 6-methyl-2-heptanone; (E)-ethen-2-d-ol; 4-anilino-4-keto-2-phenyl-butyric acid; diisobutyl (oxybis(ethane-2,1-diyl)) dicarbonate; nickel tetracarbonyl; (E)-2-ethylene-4-methylene-5-hexenal; 3-methyl-1-butyne; (R)-5-methyl-2-(1-methylethylidene)-cyclohexanone; α-propyl-benzeneethanol; 4-methyl-1-pentene; 1,3,3-trimethyl-2-oxabicyclo[2.2.2]oct-5-ene; 2,2′-(ethene-1,2-diylbis(sulfanediyl))diethanol; 3-methyl-thiophene; tert-butyl alcohol; and 2-methoxysuccinonitrile.
6 . A method according to claim 5 , wherein the at least one signature compound is selected from the group consisting of 3-ethyl-1-octene; ethyl lactate; tetramethyl succinimide; 6-methyl-2-heptanone; (E)-ethen-2-d-ol; 4-anilino-4-keto-2-phenyl-butyric acid; diisobutyl (oxybis(ethane-2,1-diyl)) dicarbonate; nickel tetracarbonyl; (E)-2-ethylene-4-methylene-5-hexenal; 3-methyl-1-butyne; (R)-5-methyl-2-(1-methylethylidene)-cyclohexanone; α-propyl-benzeneethanol; 4-methyl-1-pentene; and 1,3,3-trimethyl-2-oxabicyclo[2.2.2]oct-5-ene.
7 . A method according to claim 6 , wherein the at least one signature compound is selected from the group consisting of 3-ethyl-1-octene; ethyl lactate; tetramethyl succinimide; 6-methyl-2-heptanone; (E)-ethen-2-d-ol; 4-anilino-4-keto-2-phenyl-butyric acid; diisobutyl (oxybis(ethane-2,1-diyl)) dicarbonate; and nickel tetracarbonyl.
8 . A method according to claim 7 , wherein the at least one signature compound is selected from the group consisting of 3-ethyl-1-octene; and ethyl lactate.
9 . A method according to claim 1 , wherein the mass spectrometry comprises TOF.
10 . A method according to claim 1 , wherein the at least one signature compound is selected from the group consisting of 1-tetradecanol; 4-methyloctan-1-ol; 3-ethyl-1-octene; ethyl lactate; 6-methyl-2-heptanone; (E)-ethen-2-d-ol; (E)-2-ethylene-4-methylene-5-hexenal; 3-methyl-1-butyne; 4-methyl-1-pentene; 3-methyl-thiophene; tert-butyl alcohol; and 4,4-dimethyl-octane.