Validation and establishment of pre-identified novel gene(s) as gastric cancer biomarker(s)

INTRODUCTION

Epigenetic changes are linked with many cancer types [1]. In GC, Several genes were found to be differentially methylated compared to their adjacent normal cells of the same individual [2], and these differentially methylated genes can be used as a biomarker for GC screening, treatment, and prognosis [3].

In India, GC is responsible for about 53,253 deaths in the year 2020 and is the 6th leading cause of death [4]. 1 out of 160 men and 319 women has the risk to develop GC in their lifetime (0-70 years) [5]. Aizawl and Papumpare district of Mizoram and Arunachal Pradesh respectively has the highest incidence of GC among men and women respectively [6]. Kamrup (metro) of Assam has reported having the highest increase in APC (annual percentage change) of 6.5 in males and 11.7 in females [5].

Five Novel hypermethylated genes (PPP1R16B, FGF12, FEZF2, GDF7, and KCNQ5) were identified in the ethnic population of Mizoram form our laboratory at NEHU [7]. The primary objective of this present study is to establish these 5 genes as biomarker(s) of GC in patients from different ethnicities of Northeast India. These biomarker(s) will help clinicians better understand the disease, diagnose early and design the treatment plan accordingly.

HYPOTHESIS

The hypothesis of the study is PPP1R16B, FGF12, FEZF2, GDF7, and KCNQ5 genes are differentially methylated and have expressional differences between cancer matched-control tissues suggesting their potential utility as biomarkers for the diagnosis and prognosis of gastric cancer for different population.

OBJECTIVES

**a.**To study the degree of methylation of PPP1R16B, FGF12, FEZF2, GDF7, and KCNQ5 in cancer and matched control tissue and measure its association with different patient parameters.

**b.**To study the expression of PPP1R16B, FGF12, FEZF2, GDF7, and KCNQ5 in cancer and matched control tissue and measure its association with different patient parameters.

**c.**To calculate the association between methylation and expression of PPP1R16B, FGF12, FEZF2, GDF7, and KCNQ5 in cancer and matched control tissue.

REFERENCES

[1] Esteller, M. (2008). Epigenetics in cancer. New England Journal of Medicine, 358(11), 1148–1159.

[2] Jones, P. A., & Baylin, S. B. (2002). The fundamental role of epigenetic events in cancer. Nature Reviews Genetics, 3(6), 415–428.

[3] Locke, W. J., Guanzon, D., Ma, C., Liew, Y. J., Duesing, K. R., Fung, K. Y., & Ross, J. P. (2019). DNA methylation cancer biomarkers: Translation to the clinic. Frontiers in Genetics, 1150.

[4] IARC (2020). Globocan-2020. Retrieved from: https://gco.iarc.fr/today/data/factsheets/populations/356-india-fact-sheets.pdf

[5] Mathur, P., Sathishkumar, K., Chaturvedi, M., Das, P., Sudarshan, K. L., Santhappan, S., Nallasamy, V., John, A., Narasimhan, S., Roselind, F. S., & others. (2020). Cancer statistics, 2020: Report from national cancer registry programme, India. JCO Global Oncology, 6, 1063–1075.

[6] Shanker, N., Mathur, P., Das, P., Sathishkumar, K., Shalini, A. M., & Chaturvedi, M. (2021). Cancer scenario in North-East India & need for an appropriate research agenda. The Indian Journal of Medical Research, 154(1), 27.

[7] Lamare, F., Khongsti, S., Marthong, L., Ghosh, S., Chenkual, S., & Dkhar, H. et al. (2022). Genome-wide DNA methylation profiling of stomach cancer in the ethnic population of Mizoram, North East India. Genomics, 114(5), 110478.