Abstract
The Nobel Prize in Physiology or Medicine for the year 2021 was awarded to Ardem Patapoutian and David Julius for their discoveries of temperature-sensitive receptors (TRP channels) and tactile receptors (Piezo channels), both of which were previously unknown. TRP channels are at the heart of the human ability to detect temperature, and they also play crucial regulatory functions in the occurrence and progression of cancer. Despite this, there have been no research conducted on the prognostic significance of TRP channels in individuals with esophageal squamous cell carcinoma (ESCC). In GEO and TCGA cohorts, unsupervised clustering was first conducted based on 18 TRP channel-associated differentially expressed genes (DEGs) extracted from MSigDB database and KEGG database. Two TRP subtypes were identified and patients in subtype B had the best prognosis among the two subtypes. Significant differences in staging and grading existed among the different subtypes. In GEO cohort, univariate Cox analysis were performed to screen prognosis related genes. A TRP channel-related prognostic signature, which included 7 signature-related genes, was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were divided into a high-risk group and low-risk group by the median risk score. In GEO and TCGA cohorts, Receiver operating characteristic (ROC) curves, principal component analysis (PCA), and univariate and multivariate Cox regression were performed to confirm the validity of signature. Following a more in-depth study of the TME based on the risk signature, it was discovered that the high-risk group had higher immune cell infiltration and lower tumor purity, indicating a bad prognosis. Patients with high risk scores also had increased immune checkpoint expression, indicating that these patients may be more likely to benefit from immunotherapy than other patients. We also found that paclitaxel, cisplatin, and 5-fluorouracil displayed a better response in treating the low-risk score ESCC patients. This study also adopted GTEx and qRT-PCR to perform experimental verification processes. In summary, we identified a TRP channel-associated prognostic signature. This signature can predict prognosis and immune microenvironment in ESCC.
Highlights
Esophageal cancer is the fifth most prevalent malignancy in China and the fourth leading cause of cancer-related fatalities (Anandavadivelan and Lagergren, 2016)
120 Transient receptor potential (TRP) channel-related genes were collected for subsequent analyses
RNA-seq data from the TCGA-esophageal squamous cell carcinoma (ESCC) cohort were analyzed using the limma package (p < 0.05; |logFC| > 1.5), and a total of 18 TRP channel-associated differentially expressed genes (DEGs) were identified in 80 ESCC and 11 normal samples (Figure 1B)
Summary
Esophageal cancer is the fifth most prevalent malignancy in China and the fourth leading cause of cancer-related fatalities (Anandavadivelan and Lagergren, 2016). Esophageal cancer may be classified into two subgroups based on its histological characteristics: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) (Smyth et al, 2017). ESCC accounts for nearly 90 percent of all esophageal cancer occurrences in China and is the most frequent histologic form of the disease (He et al, 2020). Despite the breakthroughs in the diagnosis, prognosis, and treatment of ESCC, early diagnosis still remains poor, with a 5-year overall survival rate less than 20% in some cases (Yang et al, 2020). The occurrence and development of ESCC relies on multiple factors, stages, and genes. Both genetic and environmental factors affect the development of this disease (Abnet et al, 2018).
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