**4. Tumor biomarkers**

Histological examination of tissue biopsy has been the most commonly used procedure for the diagnosis of bone tumors. Clinical and radiological observations also aid in diagnosis and provide a complete staging of bone cancers. But molecular and genetic markers increase the accuracy of diagnosis, assist in subtyping bone tumors, and also provide an overview of target molecules for designing therapeutic approaches. The biomarkers can be specific or non-specific; diagnostic, prognostic, or therapeutic; and serological, genetic, or histological. The clinical presentation of bone tumors is non-specific, and the most common symptoms include pain and swelling. The clinical features involve limited movement, skin hyperthermia, weight loss, and the presence of a visible mass in the anatomical profile [10].

The serological markers are generally a reflection of osteoblastic and osteoclastic activities in the bone [10]. As mentioned in the earlier sections, breast cancer metastases are mostly osteolytic, whereas metastases of prostate cancer are generally osteoblastic. Therefore, elevated levels of urinary N-terminal cross-linked telopeptide (NTx of type I collagen) and serum carboxyterminal cross-linked telopeptide (ICTP of type I collagen) in solid tumor patients and serum tartrate-resistant acid phosphatase type 5b (TRAcP-5b) in patients with breast tumor metastasis can be used for diagnosis. On the other hand, serum levels of bone-specific alkaline phosphatase (BSAP), procollagen type I N-terminal propeptide (PINP), and OPG serve as the biomarkers for prostate cancer metastasis [10, 30].

With reference to the genetic changes, sarcomas can be divided into three categories: sarcomas with specific translocations (e.g., Ewing's sarcoma, aneurysmal bone cyst), tumors with gene mutations or amplifications (e.g., chondrosarcomas, fibrous dysplasia), and sarcomas with genetic instability. These cytogenetic changes can be detected using banding and multicolor fluorescence in situ hybridization (FISH), array comparative genomic hybridization (array CGH), targeted detection techniques such as qPCR, and techniques to detect mutation [10].

There are several markers that are used for prognosis or diagnosis of different types of tumors that are discussed below:

#### **4.1 Osteosarcoma**

#### *4.1.1 Serum markers*

1.Degradation of collagen and the ground substance in the bone (due to prolonged exposure to fluoride) results in increased concentration of serum sialic acid that can be used as a serum biomarker for osteosarcoma [10].

**21**

*Bone Tumors: Types and Treatments*

malignancy [10].

sarcoma [10].

*4.1.2 Genetic markers*

osteosarcoma [10].

*DOI: http://dx.doi.org/10.5772/intechopen.86550*

2.Expression of heat shock protein (HSP gp96), in the cytoplasm of osteoblastic sarcoma, has been found to be associated with pathogenesis of bone tumors. But it does not provide any idea regarding the degree of

3.The osteosarcoma patients displayed increased levels of endostatin, placental

metabolites in urine and serum samples of osteosarcoma patients displayed a disrupted energy metabolism, downregulated amino acid metabolism, and

increased expression in osteosarcoma tissues, suggesting it as a prognostic marker. Western blotting and enzyme-linked immunosorbent assay (ELISA) confirmed a

growth factor (PlGF), and FGF-1 and FGF-2 in serum [10].

4.Gas chromatography–mass spectrometry profiles of small-molecule

increase in glutathione metabolism and polyamine metabolism [10].

5. qPCR and western blot analysis for detection of IGF-1 receptor showed its

decrease in serum levels of gelsolin in the osteosarcoma samples [10].

is also useful in prognosis of bone tumors [10].

6.The presence of FGF-2 or leukemia inhibitory factor (Lif) serves as a biomarker, suggesting reduction of osteogenesis on osteosarcoma cells. Elevated serum levels of CXCL4 and CXCL in osteosarcoma patients affirmed the role of these markers in clinical manifestation. In addition to this, biomarker Snail2

7.Metastatic prostate cancers have been found to express the well-known markers of aggressiveness, namely, prostatic-specific antigen (PSA) [30].

8.Increase in erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) are indicators of osteosarcoma [1, 12].

9.Immunohistochemistry of primary osteosarcomas showed expression of mitotic arrest defective protein 2 (MAD2). Immunohistochemical analysis of osteosarcoma biopsies indicated reduced expression of cysteine-rich protein with Kazal motifs (RECK). Immunohistochemistry analysis also showed expression of WNT-5a and ROR2 in patients with advanced stages of osteo-

Assessment of *CCN3* expression levels at diagnosis may represent a useful molecular tool for early identification of patients with osteosarcoma. Gene alteration of c-kit protein also serves as a prognostic marker for osteosarcoma. The transcriptional regulator, Oct-4, has been found to play a marked role in proliferation and spread of cancer. A reduced expression and inactivation of miR-34 gene have been reported to be associated with osteosarcomas. The action of miR-34 is p53 dependent. A dominant polymorphic variant of TGFβ receptor 1 (TGFBR1), TGFBR1\*6A, is found to be associated with increased susceptibility of osteosarcoma for metastasis. Bcl-xL, a member of Bcl-2 (B-cell lymphoma (BCL)) protein family, has been investigated to function as a dominant regulator of apoptotic cell death and plays an important role in malignant transformation. Cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule that decreases immune response mediated by T cells, promotes development of osteosarcoma. Overexpressions of *Cortactin* (*CTTN*) gene, present in 11q13 amplicon, serve as a valid biomarker for
