Overexpression of Transient Receptor Protein Cation Channel Subfamily A Member 1, Confers an Independent Prognostic Indicator in Nasopharyngeal Carcinoma

Abstract

Background: Detection of oncogenes provides chances to understand tumor development and progression. Transient receptor protein cation channel subfamily A, member 1 (TRPA1) transcript was significantly upregulated in nasopharyngeal carcinoma (NPC) with a stepwise upregulation from low- to high-stage NPCs from a preliminary data analysis in the Gene Expression Omnibus database. The TRPA1 gene is a member of the TRP channel family, encoding integral membrane proteins that functions as cation channels. Loss of calcium homeostasis takes place in cancer cells.Methods: Immunostaining of TRPA1 was analyzed on 124 biopsies from NPC patients retrospectively. The H-score method was used to evaluate the immunoexpression of TRPA1. The correlations between H-score of TRPA1 protein level and clinicopathological factors, as well as the significances of TRPA1 protein level for disease-specific, distal-metastasis-free and local recurrence-free survivals were assessed.Results: These patients were characterized to be no initial metastasis and medicated with the traditional procedure. The TRPA1 score was found to be associated with clinicopathological parameters and patient survivals. Along with the guideline of 7th edition of the American Joint Committee on Cancer, we found that TRPA1 upregulation (50%) was associated with advanced primary tumor (P = 0.009) and overall clinical stage (P = 0.019). In univariate log-rank testing, primary tumor, nodal status, stage and TRPA1 protein level significantly contributed to worse disease-specific survival, distal metastasis-free survival and local recurrence-free survival. In multivariate analysis, high TRPA1 protein level and tumor stage emerged as independent prognostic indicators for inferior disease-specific survival (P = 0.014; P = 0.003), distal metastasis-free survival (P = 0.004; P = 0.034) and recurrence-free survival (P = 0.017; P = 0.015).Conclusions: The upregulation of TRPA1 protein level is frequently correlated to unfavorable prognosticators and gives rise to cancer progression in NPC patients.

TRPA1–FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

“…TRPA1 mediated protein–protein interactions, their consequent regulatory effects, and roles in LUAD remain largely unknown. Interestingly, the role of TRPA1 as an invasive and prognostic marker in cancer 12 , 48 has recently been reported, reflecting the growing interest in deciphering its oncogenic function. By building on the previously established role of FGFR2 in LUAD 17 – 19 and the possibility of ankyrin repeats binding to proline-rich motifs 15 , we investigated the presence of a potential TRPA1-FGFR2 binding event in LUAD and its contribution to the oncogenic process.…”

Periostin overexpression is associated with worse prognosis in nasopharyngeal carcinoma from endemic area: a cohort study

“…Tissue sections were cut from paraffin-embedded blocks at 3 μm thickness as described previously. 13 , 14 Slides were processed followed by deparaffinization, rehydration, antigen retrieval, and blockage of endogenous peroxidase. Subsequently, the sections were incubated with the primary antibody against POSTN (1:100; Lifespan BioScience, Seattle, WA, USA, Cat No LS-B3986) for 1 hour.…”

Transient Receptor Potential (TRP) Channels in Head-and-Neck Squamous Cell Carcinomas: Diagnostic, Prognostic, and Therapeutic Potentials

“…For instance, TRPV1 expression is increased in HNSCC [ 3 ] and prostate cancer [ 132 ] but is markedly reduced or absent in renal cell carcinoma [ 102 ] or urothelial carcinoma [ 116 ]. Moreover, TRPV2 overexpression heralds poor prognosis in esophageal SCC [ 105 ], but identifies a subgroup of triple-negative breast cancer patients with favorable prognosis [ 114 ]. Therefore, observations done in one type of cancer cannot be extrapolated to a different type of cancer.…”

“…TRPA1-like immunopositivity is upregulated in human NPC samples, with negative predictive value for disease-specific, metastasis-, and local recurrence-free survival. If confirmed in independent studies, TRPA1-like immunoreactivity could be a valuable prognostic marker in HNSCC patients treated by irradiation and adjuvant cisplatin chemotherapy [ 105 ].…”

“…TRPA1 is another intriguing target to explore. Similarly to TRPV1, it is highly expressed in HNSCC cells [ 105 ], and potent TRPA1 agonists are readily available for the studies ( Figure 1 B).…”