*3.3.4 HSP70*

HSP70 has 13 subgroup family members. It is associated with cytosolic calcium level homeostasis and, inhibition of HSP70 expression, has been shown to stimulate release of intra-cellular calcium in cell culture. Calcium induces cell death by the caspase dependent mechanism in CRC cell lines, and functions in the stabilization of lysosomes and inhibition of apoptosis [84]. Importantly, in other types of cancer such as pancreatic and prostate cancer, HSP70 has been shown to upregulate cell survival [84]. In a study of 33 CRC patient plasma samples, using ELISA assays, serum levels of HSP70 were significantly elevated (≥2.25 ng/ml) in cancer patients compared to healthy controls, The sensitivity and specificity of elevated serum HSP70 in the CRC group was reported as 96.77% and 96.96% respectively [85]. It has been further demonstrated using ELISA testing that high serum concentration of HSP70 is associated with increased mortality (p = 0.005) [86]. Additionally the use of immunostaining has shown that mitochondrial HSP70 overexpression correlates to poor survival (p = 0.04) [87]. Independent IHC analyses of 81 primary CRC tissues revealed that HSP70, as well as HSP110, overexpression is associated with highly advanced clinical stages and positive lymph node involvement [88].
