Biomarker Genes for Gynaecological Cancers

 

Vimlendu Bhushan Sinha*, Neha Pandey, Pankaj Taneja

Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida, Uttar Pradesh-201306, India.

 

 

ABSTRACT:

Cancer is disease of uncontrolled cell proliferation. In the current set of investigation, data available on C-bioportal was used for enlist the biomarker genes in breast, ovarian and cervical cancers. A total of 29 biomarkers having potential for  long term use in therapeutic developments were identified. Few prominent ones for breast cancer like BRCA1, ER, PR and Her2/neu, Ki67, PCNA in breast cancer prognosis,  M-CSF, FSH and SMRP, CA-125, HE-4, mesothelin and GST, FOLRI and ALDH1, p53, Ki67, PCNA for monitoring ovarian cancer, HPV E6, E7, MCM, CDC6, P¹⁶INK^4A and PCNA. Ki67 for tumor aggressiveness and metastatic potential of cervical cancer was identified. The current manuscript elucidates the importance and detection of gynecological cancer using biomarkers as a fast and reliable way for early disease detection.

 

 

 

 

INTRODUCTION

Cancer (classified as benign and malignant forms) works at genetic level, involves abnormal cell growth of the cells, needs proper nutrition with specific microenvironment and angiogenesis potential in metastasis spread, disrupting normal cells for increased proliferation from one part of the body to another^1,2 .  About 35,000 genes in human genome have been reported to have association with cancer and even a single alteration in a gene may be resulting into causes cancer³. The understanding of heterogeneity of the cancerous cells is thus important as a preferred step for avoiding the drugs which increase mutations, alterations or any kind of anueploidy^4,5. Ovarian cancer, cervical cancer and breast cancer are the three types of gynecological cancer known so far and markers are helpful in easy identification⁶.  Previous reports indicate(s) that the cancer progression and the response of the treatment can be predicted by biomarkers⁷.

 

Usually markers are several types of proteins which can be distinguished among four types, namely biochemical, molecular, physiological and anatomical markers⁸. The peculiarity about all these markers is that these marker(s) can diagnose the cancer in an early stage and the level of lethality can be accessed easily. A metabolite or any kind of secretion from tumor or their metabolic pathway or the process can be used as a biomarker for cancer which can help in diagnosing cancer and prediction of the response of therapies towards patients. Moreover, it becomes possible that these markers can also predict the response of the treatment to a particular patient. These can be found in several body parts like fluids of the body (blood, serum, urine, saliva, stool etc.) and tissues (sample of tissues from the body). Recently, cancer markers have been detected in breath odour and are known as Volatile Organic Compound (VOC) type of markers⁹. Various omics related technologies primarily detects the gene and have various applications in the field of genomics, transcriptomics, proteomics and metabolomics. All these especially metabolomics is competent and facilitates the discovery of biomarkers for cancer¹⁰. Although a series of work has been done so far for identification and characterization of markers related to gynecological issues but yet a clear picture for compiled marker list is missing at one place. Considering these shortcomings, the current study was started with the objective of marker identification related to disease progression and/or survival and their listing so that it could be utilized further for human welfare.

 

 

Table 1: Biomarkers identified for gynaecological cancer

S. No.	Biomarker	Type of Cancer	Potential utility	Reference
1	BRCA1/2	Breast	Used as a novel potential predictive biomarker for determining the differential chemo-sensitivity at both preclinical and clinical stage.	14
2	HER-2/NEU	Breast	Used to measure HER-2/neu status in breast cancer clinical samples	15
3	ER/PR	Breast	Used as prognostic/predictive biomarkers for clinical use in breast cancer	16
4	TP53	Ovarian	Could be used as a biomarker for malignant progression.	17
5	MLH1	Ovarian	Used as a  potential biomarker of risk for colorectal neoplasms	18
6	MSH2	Ovarian	Could be used as a potential modifiable biomarker of risk for colorectal neoplasms.	19
7	MMP	Ovarian	Could be used as diagnostic/prognostic biomarker with disseminated peritoneal/pulmonary metastasis	20
8	MIF	Ovarian	Used as a  biomarker in diagnosing renal involvement in children with SLE	21
9	EGFR	Ovarian	Could be used as a potential predictive biomarkers	22
10	M-CSF	Ovarian	Used as a multiple biomarkers improve sensitivity in women at high risk for ovarian cancer.	23
11	FSH	Ovarian	Could be used as a biomarker for estimating the day of ovulation in population based studies	24
12	SMRP	Ovarian	Used for screening asbestos exposed populations, monitoring treatment and predicting prognosis	25
13	CA125 (Cancer  Antigen 125)	Ovarian	Used for early detection of Ovarian Cancer	26
14	HE4 (Human Epididymis Protein 4)	Ovarian	Used as a novel serum biomarker in high risk population	27
15	Mesothelin	Ovarian	Eligible as a target for cancer therapy.	28
16	KLK (Kallikreins)	Ovarian	Could be used as tumor markers for the epithelial derived serous carcinomas.and their diagnosis and monitoring.	29
17	PRSS8	Ovarian	Used as novel biomarker for  to identify upregulated genes for secretor proteins.	30
18	Glutathione S-Transferase Polymorphism	Ovarian	Used as a novel biomarker for early detection and diagnosis of ovarian cancer	31
19	FOLR1 (Folate Receptor Alpha)	Ovarian	Used as a biomarker in     detection, prognosis, and assessing chemotherapy responses of ovarian carcinoma	32
20	miRNA	Ovarian	Used as a potential biomarkers for early detection, diagnosis, and monitoring the overall progress of the disease	33
21	ALDH1	Ovarian	Could be a possible biomarker for early detection of ovarian carcinomas	34
22	HPV E6	Cervical	Used in the screening, early diagnosis, prognostication and prediction of response to therapy.	35
23	HPV E7	Cervical	Could be used for rapidly analyze and display changes in protein expression under different conditions for neoplastic cell subpopulations.	36
24	MCM  (Mini Chromosome    Maintainance)	Cervical	Used as a potential biomarker   for cervical dysplasia	37
25	CDC6 (Cell Division Cycle    Protein 6)	Cervical	Could be a biomarker of high grade and invasive lesions of the crvix with limited use in low grade dysplasia	38
26	SCC (Squamous Cell Carcinoma Antigen)	Cervical	Could be used for monitoring the early detection of recurrent or progressive disease after primary treatment, and may therefore be useful in the management of patients.	39
27	PCNA	Cervical	Could be used as a marker with highly effective detector of malignancy.	40
28	Ki-67	Cervical	1.  Could be used as a biomarker for both prognostic and predictive value. 1.  May be used for  pre-analytical, analytical, and post-analytical practice  in clinical practice	41
29	P16INK4A	Cervical	1.  Could be used as a sensitive/specific marker of squamous and glandular dysplastic cells of the cervix. 2.  Used as a surrogate marker of high risk HPV suggesting a valuable adjunctive test in cervical cancer screening	42

 

 

METHODOLOGY:

Identification of Biomarkers for Ovarian/Breast/ Cervical Cancer

C-bioportal was referred and literature survey was performed to know the existing biomarkers for ovarian/ breast/cervical cancer and prediction for some other possible function of existing biomarkers.

 

RESULTS AND DISCUSSION:

The number of new registered cases for gynacological cancer and associated death observed a steep increase in last few years¹¹. Ovarian cancer is the most prevalent type of cancer and is detected usually in advanced stages¹². One of the current method of treatment for ovarian cancer is by using cytoreductive surgery combined/followed by platinum/taxane combination therapy¹³. Biomarkers can specifically diagnose cancer, irrespective of the origin of the tumor (either benign or malignant). Gynaecological cancer in human may get developed in breast, ovary, cervix, uterine wall and vagina. Specifically for breast heterogenous type of cancer with no sub-types has been observed. The various identified biomarkers from previous studies has been listed in Table 1. Although gynecological malignancies can be treated by different options and ovarian cancer is the most deadly for humans. Cancer diagnosis at an early stage is very important for survival and current diagnostic tools have only limited success for early detection. However, discovery of good and reliable novel diagnostic biomarkers/panels for possible fast/early diagnosis of ovarian cancer remains the prime challenges for modern medicine development. Considering this it can be predicted that gynecologic cancer biomarkers which are prognostic and/or can be used for fast and accurate treatment can be an active and fruitful area of investigation. Conversely, due to decrease in cost of genetic testing the number of mutational screening has increased contributing towards better strategy development. Germline mutations associated with breast cancer (BRCA1/2) predispose women to breast and ovarian cancers. BRCA1/2 deficiency, may result into abnormalities in the S-phase, G₂/M phase and centrosome duplication. When functionally analyzed, understanding of genes like BRCA1 during their involvement in genome integrity, cell cycles, tumor evolution and DNA damage response will likely help us in deciphering mechanism of BRCA1 associated tumorigenesis. This will actually help in better therapeutic approaches for these lethal disease and enhance interactive studies for searching new clinically useful biomarkers. With the progress of techniques in genomics and proteomics, promising molecular panels/biomarkers for ovarian cancer  diagnosis were identified but needs to be validated before declaring them as a potent biomarker. The article summarizes different types of bio-markers used by different workers for gynaecological cancer diagnosis including gene and/or protein based ovarian cancer indicators like microRNA etc. Before biomarker tests are translated for routine use, more researches are needed to evaluate the overall clinical utility of the tests.

 

CONCLUSION:

For gynecological cancers, only a handful of tumor associated antigens have been routinely used as biomarkers. Some markers can prove out to be useful not only as diagnostic tool but may also serve as predictive marker for the prognosis and further clinical tests. The outcome of this research can be listed as:

1.          Identification of twenty nine biomarker associated with this study which can be helpful in detection of gynaecological cancer (Breast, Ovarian, and Cervical cancer).

2.          Stratification biomarkers may be developed for facilitating disease prevention.

 

ACKNOWLEDGEMENTS

The authors are thankful to Sharda University, Greater Noida, India for the permission to carry out the work.

 

AUTHOR’S CONTRIBUTION

NP-Collected the materials and compiled the results; VBS-Planned the work, Inferred the results and drafted the manuscript; PT-Critically reviewed the manuscript and helped in finalizing the manuscript draft.

 

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Accepted on 27.07.2016           © RJPT All right reserved

Research J. Pharm. and Tech 2016; 9(10):1641-1646.