*3.3.1 HSP27*

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].

## *3.3.2 HSP40*

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 IHC and immunoblotting [79].
