## 4 Discussion  
ESCA is the most common cause of cancer death and starts in the esophageal mucosa's epithelial tissues. ESCA is the world's eighth most prevalent cancer and the sixth most lethal worldwide. The most frequent histologic subtype of ESCA in ESCC. Most of the patients affected by EC are discovered at an advanced stage and are typically incurable. Despite extensive research into the mechanisms causing ESCC, reliable biomarkers for ESCC diagnosis, prognosis, and clinical targeting are still lacking. The mechanisms regulating ESCC have still not been completely understood [48; 49]. In the present study, GEO dataset GSE161533 with high quality was selected to identify the hub genes associated with ESCC and their associated biological pathways by integrated multi-omics analysis. We chose the top 250 DEGs consisting of 136 upregulated genes, and 113 downregulated genes were identified, and they were used to construct the PPI network. Finally, we identified the HGsT10 significantly on the MCC scores in the PPI network. The expression of HGsT10 genes (namely, MMP9, MMP9, MMP1, CXCL8, SPP1, PLAU, MMP13, COL1A1, COL1A2, and PLAUR) was identified in the GSE161533 sample and validated with the TGCA dataset. The expression rate of HGsT10 was increased for all the predicted hub genes. Notably, MMP1, SPP1, and MMP13 log-transformed TPM values are highly increased compared to other HGsT10 genes. The overexpression of MMP1 promoted tumor growth and metastasis by activating the PI3K/AKT pathway [50]. Furthermore, it makes a significant contribution to the extracellular matrix remodeling that occurs during tumor progression and metastasis [51]. Likewise, SPP1 plays a crucial role in the tumor growth of ESCC and can be used as a molecular biomarker in the early detection and diagnosis [52]. Similarly, the upregulation of MMP13 by activating the ERK1/2 pathway promoted tumor progression at metastasis and transformed squamous epithelial cells across various tissues [53; 54; 55]. The expression of HGsT10 genes based on the type of diseases was predicted with the GDC TCGA ESCA patients, including 160 patient samples. The expression level of MMP9, MMP1, SPP1, PLAU, MMP13, COL1A1 and COL1A2 genes was more highly increased in the squamous cell carcinoma than other ESCA types and worsened the overall survival rate of the patients. Most of the predicted HGsT10 genes are overexpressed early, such as MMP9, MMP1, CXCL8, SPP1, PLAU, MMP13, COL1A1, and PLAUR may be used as significant biomarkers to diagnose and treat the ESCC patients at an early stage. The overall survival rate of ESCA patients was drastically decreased with the increased expression of the predicted HGsT10 genes, especially CXCL8, SPP1, PLAU, MMP13, and PLAUR. [PERSON] et al. and [PERSON] et al. stated that the MMP13 \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Group** & **Pathway Enriched** & **Gene Symbol** & **FDR** & **\(p\)-Value** & **Expected Value** & **Enrichment Ratio** \\ \hline
1. & Bladder cancer & CXCL8, MMP1 and MMP9 & 0.00212221 & 0.000019649 & 0.056633 & 52.972 \\
2. & IL-17 signaling pathway & & & & & \\  & & MMP9, MMP9 & & & & \\  & & COL1A1, COL1A2, MMP1, & & & & \\  & & MMP13, MMP9 & & & & \\
3. & Relaxin signaling pathway & & & & & \\  & & & & & & \\
4. & ECM-receptor interaction & COL1A1, COL1A2, SPP1 & 0.00089896 & 0.00015276 & 0.11185 & 26.822 \\
5. & Rheumatoid arthritis & & & & & \\
6. & Amobias & COL1A1, COL1A2, CXCL8 & 0.010116 & 0.00020423 & 0.13026 & 23.032 \\
7. & Prostate cancer & MMP9, MMP9, PLAU & 0.01016 & 0.00026419 & 0.13450 & 22.304 \\  & AGE-RAGE signaling & & & & & \\
8. & pathway in diabetic & COL1A1, COL1A2, CXCL8 & 0.010116 & 0.00028100 & 0.13734 & 21.844 \\  & complications & & & & & \\
9. & Transcriptional & & & & & \\  & & & & & & \\
10. & Focal adhesion & COL1A1, COL1A2, SPP1 & 0.061616 & 0.0020919 & 0.27325 & 10.979 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: The pathway enrichment analysis resulted in the following parameter for the predicted HGsT10 genes.