**Table 2.**

**145**

*Finding Needles in Haystacks: The Use of Quantitative Proteomics for the Early Detection…*

cancer mortality compared to non-elevated pre-operative levels [69].

Cancer (or Carbohydrate) antigen 19-9 (CA 19-9) is a clinical biomarker used in various diseases. Elevation can occur in benign conditions such as biliary and pancreatic disease, pulmonary disease, renal failure and autoimmune disease as well as malignant conditions of the pancreas, colon, rectum, liver, ovary and lung. CA 19-9 is therefore considered a non-specific biomarker of CRC [66] and is a classical marker for late stage disease and metastasis. For this reason it is not appropriate for use as a screening, or diagnostic, marker of carcinoma [67]. CA 19-9 can be used in tandem with CEA for post-operative monitoring to detect recurrence, or as a prognostic indicator as pre-operative elevation without correspond elevation of CEA is associated with a poorer 5-year survival [68]. When the combination of preoperative elevation of both CEA and CA19-9 occurs, this is predictive of increased

Heat shock proteins (HSP) are a type of stress-inducible protein that are present in all organisms [70] and their cells at low levels in normal physiological conditions. They have been functionally linked to cell apoptosis, protein homeostasis, cell growth mediation as play an important role during fertilization [70–76]. HSPs also function as chaperones, and act in protein assembly and unfolding. Various member of the HSP family have been postulated to have roles in antigen presentation and as a chaperones of peptides to major histocompatibility complex class I and class II [75, 76]. HSPs are typically classified into five subunits or families according to their molecular weight; Large HSP (HSP110, glucose-regulated protein 170), HSP90, HSP70, HSP60 and small HSPs (HSP27, HSP40). Significant research has focused around the role of HSPs in disease progression and on their role as therapeutic targets and as biomarkers.

HSP27 is a member of the small HSP family, it has an anti-apoptotic role and acts as a chaperone to prevent misfolded protein aggregation. It is considered to be modulated by mitogen-activated protein kinase through phosphorylation. Abnormal HSP27 expression has been demonstrated in various cancer types, including ovarian, prostate, breast and colon cancer, as well as non-malignant conditions such as neurological and cardiovascular disease [76]. The overexpression of HSP27 in histological colon and rectal cancer samples was assessed in a large cohort of 404 patients with 2DE and tandem mass spectrometry (MS/MS) combined with a large validation set using tissue microarrays (TMA). The authors found that overexpression of HSP27 was present in both colon and rectal cancer and associated with poorer cancer-free survival in the rectal cancer cohort [77]. Furthermore the use of immunohistochemistry (IHC) and TMA analytical approaches has revealed that high HSP27 and HSP70

are associated with poorer clinical outcomes in primary resected CRC [78].

HSP40 is also a member of the small HSP family and act as co-chaperones to HSP70. This family are further subdivided into DNAJA, DNAJB, and DNAJC; subgroups that have been shown to participate in both tumor progression or conversely, in tumor suppression in different types of cancer [75]. HSP40 overexpression in CRC has been demonstrated (along with HSP70) in 50 histological samples using

*DOI: http://dx.doi.org/10.5772/intechopen.80942*

**3.2 Cancer antigen 19-9**

**3.3 Heat shock proteins**

*3.3.1 HSP27*

*3.3.2 HSP40*

IHC and immunoblotting [79].

*Summary of CRC biomarker identification methods.* *Finding Needles in Haystacks: The Use of Quantitative Proteomics for the Early Detection… DOI: http://dx.doi.org/10.5772/intechopen.80942*
