Expression of DKK1, HOXC6, and YKT6 Genes in Subjects With Oral Squamous Cell Carcinoma Residing in Central India: A Case-Control Study

Introduction Oral squamous cell carcinoma (OSCC) is a predominant form of cancer affecting the head and neck region, accounting for the majority of cases in this category and posing a significant public health burden in Central India, where the incidence is among the highest in the country. Despite known associations with risk factors such as tobacco, alcohol, and areca nut use, the molecular mechanisms underlying OSCC progression and metastasis remain poorly understood. This study aimed to evaluate the gene expression profiles of <i>DKK1</i>, <i>HOXC6</i>, and <i>YKT6</i> in OSCC patients and explore their potential roles in tumour progression. Methods A case-control study was conducted at the All India Institute of Medical Sciences (AIIMS), Nagpur, between April 2023 and June 2024, involving 120 OSCC patients and 120 age- and gender-matched controls. Serum samples were collected for RNA extraction and RT-qPCR analysis of <i>DKK1</i>, <i>HOXC6</i>, and <i>YKT6</i>, using β-actin as a housekeeping gene. Expression differences were analysed using the 2^-ΔΔCt method and statistical tests, including t-tests and chi-square, with significance set at p<0.001. Results No significant differences in gene expression levels of <i>DKK1</i>, <i>HOXC6</i>, or <i>YKT6</i> were observed between OSCC cases and controls, or between subgroups with and without lymph node invasion. However, modifiable risk factors such as areca nut use (OR: 5.33), smoking (OR: 5.5), and alcohol consumption (OR: 9.85) were strongly associated with OSCC. The mean age of diagnosis was 57.5 years, with a male-to-female ratio of 2:1. Conclusion While <i>DKK1</i>, <i>HOXC6</i>, and <i>YKT6</i> did not demonstrate significant differential expression, the study highlights strong associations between OSCC and lifestyle-related risk factors. As the first gene expression study on OSCC in Central India, it underscores the need for larger, tissue-based studies to validate these findings and explore molecular targets for early diagnosis and immunotherapy.