**LncRNAs as Biomarkers for Melanoma**

**LncRNAs as Biomarkers for Melanoma**

Yixuan James Zheng, Ricardo Moreno Traspas and Susana Ortiz-Urda Traspas and Susana Ortiz-Urda Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

Yixuan James Zheng, Ricardo Moreno

http://dx.doi.org/10.5772/intechopen.70499

#### **Abstract**

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Melanoma is the most aggressive and serious type of skin cancer. Known for being highly malignant and metastatic, melanoma typically has low survival rates. Prognosis can be improved with an early diagnosis and a good monitoring of the disease. However, current melanoma biomarkers display severe limitations, making them inadequate for early detection of the malignancy. Therefore, it is of urgent matter for us to characterize and establish novel biomarkers with a direct application to daily clinics in order to accurately detect early american joint committee on cancer (AJCC) stages in melanoma patients, efficiently monitor the disease progression, and reliably predict the response to therapies, survival, and likely future recurrence. Long non-coding RNAs (lncRNAs) are a promising biomarker and regulator of tumor progression for many cancers. They are secreted into the bloodstream inside exosomes by a wide range of malignant cells and several of them have actually been validated as promising circulating molecular signatures of other cancer types, but not melanoma. However, in recent years there has been much research into lncRNA melanoma biomarkers, and many of them have been characterized as potentially clinically relevant.

DOI: 10.5772/intechopen.70499

**Keywords:** melanoma, biomarkers, lncRNAs, cancer, metastatic melanoma

#### **1. Introduction**

Melanoma is the most aggressive and serious type of skin cancer. Its propensity for rapid development and ease of metastasis to vital organs such as the brain, lungs, and liver make it so deadly. Additionally, the incidence of melanoma in the United States has been consistently increasing since at least the 1970s [1]. Most importantly, early diagnosis predicts longer survival and better prognosis [2, 3]. This makes efficient and accurate diagnosis of melanoma a priority for clinicians. Thus, the continued exploration for accurate and efficacious biomarkers is a priority among cancer research.

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

This chapter aims to describe various characterized and novel long non-coding RNAs (lncRNAs) as melanoma biomarkers. We will first explore the shortcomings and problems of current biomarkers and how lncRNAs can serve as the potential future for melanoma markers. We will then look at already characterized lncRNAs such as BRAF-activated non-coding RNA (BANCR), Sprouty 4 (SPRY4), HOX transcript antisense RNA (HOTAIR), Metastasis-associated lung adenocarcinoma transcript (MALAT), and Antisense non-coding RNA in the INK4 locus (ANRIL), as well as current research methods. Finally, we will discuss future perspectives and what we still need to do to adapt lncRNA for use as a melanoma biomarker.

evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention" [14]. Biomarkers are commonly used in both clinical trials and clinical practice because of its multitude of applications: as diagnostics for identifying patient conditions or diseases, as a tool for staging and characterization of disease,

LncRNAs as Biomarkers for Melanoma http://dx.doi.org/10.5772/intechopen.70499 27

Tumor markers are specifically biomarkers of cancer. They are usually proteins that are tumor-derived (produced by the tumor cells) or tumor-associated (produced by the body in response to tumor cells development) [15]. Tumor markers can appear in a variety of samples, but the most commonly used specimens for detection are blood serum and urine. Both are viable for these purposes because of the ease of collection and processing, as well as the secre-

Proteins are the most common tumor marker because of their central roles in cell signaling and influence on key molecular pathways in various cells and systems of the body. They are often most easily measurable through immunohistochemistry as certain protein levels change between normal and tumor cells. However, many other molecules can also serve as tumor markers. Cell-free circulating tumor DNA (ctDNA) were characterized in the late 1980s and since then, it has been found that ctDNA is correlated with tumor size and disease activity [16, 17]. ctDNA can be analyzed through liquid biopsies and PCR-based assays [18]. Circulating tumor cells (CTCs) are often present in advanced neoplasias that have metastatic potential and can be purified from serum on the basis of different cell surface markers compared to normal blood cells [18, 19]. Serum metabolites are small molecules secreted by tumor cells that can often serve as a signature of the tumor [20–22]. Carbohydrate expression also changes during oncogenic transformation and cancer progression and can serve as a measure of cancer stage [23–25]. This chapter will specifically examine RNA as biomarkers. In recent years, differing transcriptomes among tumor and healthy cells have become a point of emphasis. Several cancers have different noncoding RNA expression profiles in a time- and tissue-dependent manner. Changes in miRNA within a specific tissue has been shown to correlate with disease status including tumor invasiveness and metastatic potential in various cancers such as breast, colorectal, hepatic, lung, pancreatic, and prostate [26]. LncRNAs can also be used as serum

as an indicator of disease progression, or as a predictor of treatment response [14].

tumor markers, which we will examine in detail in the following section.

Much of our genome codes for RNA with no protein-coding potential. Such RNA is known as noncoding RNA. Long non-coding RNAs (lncRNAs) specifically refer to transcripts longer than 200 bp in length, and can reach up to over tens of kilobases in length. lncRNAs play a vital role in the regulation of many cellular processes especially gene-expression and posttranscriptional activity. This is in part due to their structural versatility and ability to form

**4. lncRNAs as biomarkers for cancer**

ribonucleoprotein complexes (RNPs) [27].

tion of distinctive cancer markers into these fluids.
