Article Review on Retroviruses (HERV-K Breast Cancer)

Article Review on Retroviruses (HERV-K Breast Cancer)

Abstract

Retrovirus can be endogenous or exogenous. Active and replicating endogenous retroviruses have become a stable part of human inherited genetic material. Due to multiple mutations, the viruses are viewed as without the ability to reproduce. This assumption has been overturned by the human endogenous retrovirus K (HERV-K), as demonstrated by its presence at high levels in a patient with breast cancer. The study provides a review of the article ‘Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early-stage breast cancer’ published in the international journal of cancer in 2014 by Wang-Jonning and his colleagues. The article focuses on the HERV-k and its use as a biomarker in the early detection of breast cancer. The review examines the main ideas, arguments, findings, conclusions, contradictions, and differing opinions presented in the article that supports the use of HERV- k as a biomarker in breast cancer detection. The study concludes that the findings of the article demonstrate that the human endogenous retrovirus HERV-k is found in significantly high amounts in breast cancer serums and quantity low in ordinary breast serums. The findings also show significant evidence that supports the use of HERV-k as a biomarker of early breast cancer (DCSI) similar to other biomarkers used in the detection of cervical cancer such as HPV 16 or 18. HERV-K antibodies and proteins mRNA acts as serum biomarkers in early-stage breast cancer.

Article Review on Retroviruses (HERV-K Breast Cancer)

Introduction

Breast cancer is a common health problem and a leading cause of death among women in the world. Breast cancer unique characteristics such as heterogeneity, complex etiology and determination of reasons, different genetic mutations, and its distinct set of clinical manifestations call for a new way of recognition of new biomarkers to facilitate early detection, improved treatment to reduce mortality (Bannert et al., 2018).  According to Zhao et al. (2011), coming up with new biomarkers remains a challenge for clinicians due to the wide variety of external and internal risk factors that are involved in the development of breast cancer. External risk factors for breast cancer include drug abuse: smoking and alcohol consumption, and the level of melatonin hormone, while internal risk factors are genetically and epigenetic (Wang-Johanning et al., 2014). The internal risk factors signal the need to develop ways in which genes can be regulated in the detection and treatment of breast cancer.

Wang-Johanning et al. (2014) suggest that the pathogenesis of breast cancer is influenced by several factors that play a critical role. The Human endogenous retrovirus (HERV) has a fundamental role in the indication and progression of breast cancer, especially in the early stages. According to Johanning et al., (2017), the virus stimulates neoplastic cells to multiply continuously. The virus also evades apoptosis- the orderly process of cell packaging into small packages for their programmed death by immune cells. HERV-K has also successfully transmitted as a host genome and its constitution in the human genome at 8%. With a history of long terminal repeats sequence (Zhao et al., 2011). HERV has gained control and regulation of structural genes with the ability to initiate autoimmune diseases and cause different types of cancers. Findings on the progression of breast cancer indicate that the Human endogenous retrovirus families are important risk factors in the stimulation of cancer cells and influencing their expansion to other tissues. Therefore, HERV-k antibodies and mRNA are promising biomarkers in the diagnosis of cancer. (Wang-Johanning et al., 2014)

Arguments

The article describes retroviruses such as HERV are made up of gag, pol, and env genes with similarities to genes in exogenous retroviruses such as HIV and the human leukemia virus (HTLV) (Wang-Johanning et al., 2003). HERV is bound together by long terminal repeats and acts as retroviral promoters. HERV has a special relationship with humans and is linked with various diseases and disorders but marked for potential benefits in humans. Research shows that multiple subtypes of breast cancers show different expressions of HERV-k.

The study classifies breast cancer as Ductal carcinoma in situ (DCIS), which is the zero stage of breast cancer and invasive ductal carcinoma (IDC) with subsequent development of the stages of breast cancer. The study uses serum anti-HERV-k eve, which shows a significantly high level of antibodies in women with DCSI and IDC (Wang-Johanning et al., 2014). However, further stratification of the women indicates considerably higher antibodies for patients with early breast cancer DCSI, which suggests that the antibody is a biomarker for early-stage breast cancer. Further, the study examines antibodies against HERV-K using Rec protein and Np9 proteins (Wang-Johanning et al., 2008). Rec protein is used to induce carcinoma citu, while Np9 is overproduced in cancers, including breast cancer. The results showed that women with DCSI increased serum antibodies against Rec protein. Thus, the presence of anti- Rec serum antibodies acts as a marker of the existence of DCSI by acting as an anti-HERV env antibody (Contreras-Galindo et al., 2008). Additionally, the presence of Np9 antibodies in the serum of DSCI patients in significantly high levels further supports the report findings that mRNA and proteins obtained from HERV-K such as REC and Np9 indicates HERV-k is a serum-based biomarker used in the detection of breast cancer in its early stages (Wang-Johanning et al., 2014).

The goal of the article is to predict a biomarker for breast cancer with an ability to detect early breast cancer as well as forecast the likelihood of metastatic breast cancer in patients through screening. The articles evaluate HERV-k role as a etiological agent of breast cancer, its involvement in the progression of breast cancer, role in early detection, and its relationship with Metastatic disease (Wang-Johanning et al., 2014). (Golan et al., 2008) infers that as a causative agent of breast cancer, the article describes that elements of endogenous retrovirus HERV-k can be found in the plasma of patients with breast cancer. The article emphasizes screening for HERV-k, and its expression shows an increase in promise for early detection of women who at risk of breast cancer.

The article also cites HERV-k in the involvement, onset, and promotion of carcinogenesis; initiation, development, and progression through its ability to cause irreversible genetic alterations. HERV-k antibodies and mRNA were elevated in blood samples of patients who were at the early stages of breast cancer. Thus, HERV derived nucleic acids have an increasingly adverse effect on breast cancer cells, which influence their development and progression in patients (Wang-Johanning et al., 2014).

HERV-k is a biomarker for early diagnosis of breast cancer. The lack of comparable tests for early detection of breast cancer compared to other tests such as cervical where a positive test of HPV 16 and 18 indicate increased risk of prostate cancer where a specific level of antigen shows malignant prostate cells furthers highlights the significance of HERVE-k (Johanning et al., 2017). The article there speculates that the use of antibodies against serum HERV‐K (HML‐2) or serum HERV‐K (HML‐2) mRNA or the combination of both indicates the presence of early-stage breast cancer (Wang-Johanning et al., 2014).

In marking the relationship between HERV-k and development of Metastatic breast cancer disease. The article insinuates that HERV-K (HML-2) antibodies and mRNA are elevated in the blood of patients at an early stage of breast cancer (Johanning et al., 2017). As a result, the study provides evidence of HERV-k gag and mRNA in serum as useful biomarkers in breast cancer metastasis.  HERV-k is higher in patients whose cancer metastasizes compares to patients whose cancer does not metastasis. Thus, higher HERV-k in patients with breast cancer presents a high chance of increases the risk of developing metastatic breast cancer by the research findings that patients who later develop metastatic breast cancer have more top HERV-k gag (Wang-Johanning et al., 2014).

Findings

Evaluations of findings of the report show that the expression of HERV-K using mRNA is increased to 70-80% in breast cancers compared to other normal (Wang-Johanning et al., 2003). Lab results indicate that HERV-k env gene is expressed in breast cancer with increases expressions seen in the preneoplastic breast lesions and   HERV-k protein, as shown by surgical specimens of breast ductal epithelial tumors. Analysis indicates the HERV-k was immunogenic in human breast cancer (Johanning et al., 2017). The article concludes that breast tissues with cancerous cells show a strong expression of HERV-k protein compared to the healthy breast tissues. Anti- HERV-k antibodies are used in diagnosis mainly to show chemotherapy success.  The article concludes that the circulation of antibodies HERV-k and HERV-mRNA in a breast cancer patient is essential, especially in the early stages of the disease because it serves as a screening tool and helps to detect cancer before advancement to critical stages (Golan et al., 2008).

The article position on HRVE- K is its importance as a biomarker in the early detection of breast cancer. Using HERV-K as a biomarker of breast cancer is demonstrated by its expression in high levels in breast cancer tissues and deficient levels in healthy breast tissues (Wang-Johanning et al., 2014). However, the article proposes that the use of serum samples, both env and gag genes expressed by mRNA, needs further future evaluation and further confirmation of the gag gene as a biomarker for early detection of breast cancer.

Study conclusions

HERV-k is a target for cancer treatment. The understanding that endogenous retroviral sequences concealed in all humans are usually reawakened during the early stages of breast cancer. In addition, the levels present in the early stages of breast cancer can be effectively used in the prediction of metastasis. The study, therefore, highlights a vital discussion and analysis by proposing HERV-k retrovirus as a biomarker in early diagnosis of breast cancer, which has not been done before (Wang-Johanning et al., 2014). Previous biomarkers for breast cancer include hormones, growth factors, methylated genes, among others. Compared to other biomarkers, the study cites the use of HERV-k as a biomarker as more effective due to its detection in large numbers, early appearance in breast cancer, and significant low amount in normal breast serum (Golan et al., 2008). HERV- K antibodies and RNA serum analysis will enhance the provision of quality health care as clinicians will be able to quickly identify women with early breast cancer and offer early treatment before cancer metastasizes and spreads to other areas of the body. The study’s future aspiration is to distinguish whether env mRNA is also predicted metastasis. The study also sees to test whether gag mRNA differs in results seen in DCIS and invasive breast cancer (Wang-Johanning et al., 2014).

Positive aspects

The article claims that HERV-k serum antibodies and mRNA levels will be useful in breast cancer screening for the following sets of women

• Women who cannot or will not be screened using mammography
• Younger women
• Women with increased risk for breast cancer such as those with a family history of breast cancer
• Women who gave birth after the age of 30
• Women with genetic mutations which increase their risk of cancer.
• Women with recurring breast tumors.

Gaps

The activation of HERV-K in the genome of breast tumors may engage a set of signaling pathways that causes poor clinical outcomes. The study finds that many breast cancer antigens tested in clinical trials are overexpressed tissue differentiation antigens, which are likely to produce poor results. The study proposes that the use of viral antigens compared to self-antigens concluding that their foreign nature is better suited for cell responses. The study claims to prove the use of serum antibody or the viral mRNA in women with recurrent breast cancer, arguing that treatment will lower serum developed in the study will effectively shrink the tumor.

Contradictions

Overexpression of HERV-k in showing higher specificity and sensitivity as a biomarker as indicated by the low levels in healthy breast tissues compared to breast cancer tissue. The article shows a contradiction by indicating that the expression of the biomarker protein is expressed in both normal and cancerous breast tissue. The contradiction triggers the need to determine if HERV-K mRNAs and antibodies are present in prediagnostic breast cancer serum, as is the case for other antigens in breast cancer serum.

Inconsistencies and Differing opinions

Various groups have proposed consideration of HERV as a vaccine in breast cancer treatment and its use as a biomarker with evidence to support its critical role in breast cancer. On the other hand, recent studies examining the prevalence of HERV-k in breast cancer patients failed to establish significant differences in individuals diagnosed with breast cancer and those without a history of the disease (Wang-Johanning et al., 2008). However, the authors point out that their findings do not rule out the presence of HERV-K in breast cancer or its use as serum biomarkers in the early stages of breast cancer.

Conclusion

HERV-k can be used as a potential biomarker, diagnostic procedures, other purposes such as vaccines. There exists a secure connection between HERV-k antibodies and clinical manifestation of early breast cancer. In experiments, antibodies used to recognize the HERV-k proteins are low in the serum of healthy donors and relatively high in the serum of women with early-stage breast cancer. Data from the study thus shows a correlation between the presence of HERV-k antibodies and breast cancer in the early stages (Wang-Johanning et al., 2014). The article highlights the reawakening of the HERV-k virus and its subsequent use as a biomarker in breast cancer patients.

More research, however, needs to be conducted on the retrovirus on aspects such as its role as a causative agent and the ability to predict Metastasis of breast cancer based on the levels of HERV-k in serums of breast cancer and normal breast. Failure to find a relationship between HERV-k and the development of breast cancer will lead to effective implementation as a biomarker for breast cancer. Based on the study, HERVE-k has a mew established role as a biomarker, which has the intense implication of early detection of breast cancer as well as metastasis to subsequent stages. Analysis of the serum should focus on HERV-k antibodies and RNA, which are the key to clinical identification of breast cancer in its early stages before spreading to other areas.

References

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