Abstract:Background
OPN3 upregulation associated with metastasis was recently described in two subtypes of lung cancers. And OPN3 identified in light‐independent functions in epidermal melanocytes has already shown promise. However, in malignant melanocytic tissues, the expression and characterization of OPN3 remain uncharacterized.
Objectives
We investigated the clinico‐histopathologic features in relation to OPN3 expression of acral lentiginous melanoma (ALM), which is a rare cutaneous melanoma subtype and not associ… Show more
“…2 B), indicating that high OPN3 expression was associated with poor survival. Considering that OPN3 expression and its association with clinicopathological features and prognosis in lung cancer and melanoma have been reported [ 5 , 7 ], in the next section, the characteristics of OPN3 among the other five cancer types are the primary focus. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…TGFβ2 is able to upregulate the tyrosinase activity of melanocytes through the light-independent function of OPN3 in a TGFβ2 receptor-independent manner [ 26 ]. In human tumours, previous studies showed that the OPN3 gene was upregulated in lung adenocarcinoma and skin melanoma, which was associated with the metastatic phenotype and unfavourable prognosis [ 5 – 7 ]. Additionally, another light-independent function of OPN3 was that its depletion triggered 5-fluorouracil resistance in liver cancer cells via the antiapoptotic pathway [ 8 ].…”
Section: Discussionmentioning
confidence: 99%
“…Details about the methods and further the semiquantitative assessment followed previous reports [ 7 ]. Briefly, 4 μm sections with different types of tumour tissues were dewaxed and rehydrated according to standard methods.…”
Section: Methodsmentioning
confidence: 99%
“…Opsin 3 (OPN3), also known as encephalopsin, was first identified as an extraocular opsin [ 2 ], which has been demonstrated to be associated with light-independent functions such as the regulation of melanogenesis and apoptosis in epidermal melanocytes [ 3 , 4 ]. Notably, it has been found that functional links between OPN3 and tumorigenesis of lung cancer, skin melanoma and clinical prognosis [ 5 – 7 ]. For lung cancers, overexpression of OPN3 was shown to promote epithelial-mesenchymal transition and metastasis in lung adenocarcinoma [ 5 ].…”
Section: Introductionmentioning
confidence: 99%
“…OPN3 was also upregulated among patients with postoperative recurrence of pulmonary carcinoid tumours [ 6 ]. Recently, a study found that high expression of OPN3 was involved in the metastatic phenotype and a poor prognosis in acral lentiginous melanoma [ 7 ]. Moreover, a previous study revealed that OPN3 was associated with 5-fluorouracil resistance in hepatocellular carcinoma cells, as its depletion activated the antiapoptotic pathway and ultimately influenced hepatocellular carcinoma sensitivity to chemotherapy [ 8 ].…”
Background
Emerging cell- or tissue-based evidence has demonstrated that opsin 3 (OPN3) mediates a variety of pathological processes affecting tumorigenesis, clinical prognosis, and treatment resistance in some cancers. However, a comprehensive analysis of OPN3 across human cancers is unavailable. Therefore, a pancancer analysis of OPN3 expression was performed and its potential oncogenic roles were explored.
Methods
The expression and characterization of OPN3 were evaluated among 33 tumour types using The Cancer Genome Atlas (TCGA) dataset. Additionally, the OPN3 RNA level and overall survival (OS) in relation to its expression level in 33 cancer types were estimated. Based on the analysis above, 347 samples from 5 types of tumours were collected and detected for the protein expression of OPN3 by immunohistochemical assay. Furthermore, the biological role of OPN3 in cancers was evaluated via gene set enrichment analysis (GSEA).
Results
The OPN3 expression level was heterogeneous across cancers, yet a remarkable difference existed between OPN3 expression and patient overall survival among the 7 types of these 33 cancers. Consistently, a high immunohistochemical score of OPN3 was significantly associated with a poor prognosis among patients with 5 types of tumours. Additionally, OPN3 expression was involved in cancer-associated fibroblast infiltration in 5 types of tumours, and promoter hypomethylation of OPN3 was observed in 3 tumour types. Additionally, OPN3 protein phosphorylation sites of Tyr140 and Ser380 were identified via posttranscriptional modification analysis, suggesting the potential function of Tyr140 and Ser380 phosphorylation in tumorigenesis. Furthermore, the enrichment analysis was mainly concentrated in C7orf70, C7orf25 and the “ribosome” pathway by GSEA in 5 types of cancers, indicating that OPN3 might affect tumorigenesis and progression by regulating gene expression and ribosome biogenesis.
Conclusions
High expression of OPN3 was significantly associated with a poor clinical prognosis in five types of cancers. Its molecular function was closely associated with the ribosomal pathway.
“…2 B), indicating that high OPN3 expression was associated with poor survival. Considering that OPN3 expression and its association with clinicopathological features and prognosis in lung cancer and melanoma have been reported [ 5 , 7 ], in the next section, the characteristics of OPN3 among the other five cancer types are the primary focus. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…TGFβ2 is able to upregulate the tyrosinase activity of melanocytes through the light-independent function of OPN3 in a TGFβ2 receptor-independent manner [ 26 ]. In human tumours, previous studies showed that the OPN3 gene was upregulated in lung adenocarcinoma and skin melanoma, which was associated with the metastatic phenotype and unfavourable prognosis [ 5 – 7 ]. Additionally, another light-independent function of OPN3 was that its depletion triggered 5-fluorouracil resistance in liver cancer cells via the antiapoptotic pathway [ 8 ].…”
Section: Discussionmentioning
confidence: 99%
“…Details about the methods and further the semiquantitative assessment followed previous reports [ 7 ]. Briefly, 4 μm sections with different types of tumour tissues were dewaxed and rehydrated according to standard methods.…”
Section: Methodsmentioning
confidence: 99%
“…Opsin 3 (OPN3), also known as encephalopsin, was first identified as an extraocular opsin [ 2 ], which has been demonstrated to be associated with light-independent functions such as the regulation of melanogenesis and apoptosis in epidermal melanocytes [ 3 , 4 ]. Notably, it has been found that functional links between OPN3 and tumorigenesis of lung cancer, skin melanoma and clinical prognosis [ 5 – 7 ]. For lung cancers, overexpression of OPN3 was shown to promote epithelial-mesenchymal transition and metastasis in lung adenocarcinoma [ 5 ].…”
Section: Introductionmentioning
confidence: 99%
“…OPN3 was also upregulated among patients with postoperative recurrence of pulmonary carcinoid tumours [ 6 ]. Recently, a study found that high expression of OPN3 was involved in the metastatic phenotype and a poor prognosis in acral lentiginous melanoma [ 7 ]. Moreover, a previous study revealed that OPN3 was associated with 5-fluorouracil resistance in hepatocellular carcinoma cells, as its depletion activated the antiapoptotic pathway and ultimately influenced hepatocellular carcinoma sensitivity to chemotherapy [ 8 ].…”
Background
Emerging cell- or tissue-based evidence has demonstrated that opsin 3 (OPN3) mediates a variety of pathological processes affecting tumorigenesis, clinical prognosis, and treatment resistance in some cancers. However, a comprehensive analysis of OPN3 across human cancers is unavailable. Therefore, a pancancer analysis of OPN3 expression was performed and its potential oncogenic roles were explored.
Methods
The expression and characterization of OPN3 were evaluated among 33 tumour types using The Cancer Genome Atlas (TCGA) dataset. Additionally, the OPN3 RNA level and overall survival (OS) in relation to its expression level in 33 cancer types were estimated. Based on the analysis above, 347 samples from 5 types of tumours were collected and detected for the protein expression of OPN3 by immunohistochemical assay. Furthermore, the biological role of OPN3 in cancers was evaluated via gene set enrichment analysis (GSEA).
Results
The OPN3 expression level was heterogeneous across cancers, yet a remarkable difference existed between OPN3 expression and patient overall survival among the 7 types of these 33 cancers. Consistently, a high immunohistochemical score of OPN3 was significantly associated with a poor prognosis among patients with 5 types of tumours. Additionally, OPN3 expression was involved in cancer-associated fibroblast infiltration in 5 types of tumours, and promoter hypomethylation of OPN3 was observed in 3 tumour types. Additionally, OPN3 protein phosphorylation sites of Tyr140 and Ser380 were identified via posttranscriptional modification analysis, suggesting the potential function of Tyr140 and Ser380 phosphorylation in tumorigenesis. Furthermore, the enrichment analysis was mainly concentrated in C7orf70, C7orf25 and the “ribosome” pathway by GSEA in 5 types of cancers, indicating that OPN3 might affect tumorigenesis and progression by regulating gene expression and ribosome biogenesis.
Conclusions
High expression of OPN3 was significantly associated with a poor clinical prognosis in five types of cancers. Its molecular function was closely associated with the ribosomal pathway.
Background
OPN3 upregulation associated with metastasis was recently described in two subtypes of lung cancers. And OPN3 identified in light‐independent functions in epidermal melanocytes has already shown promise. However, in malignant melanocytic tissues, the expression and characterization of OPN3 remain uncharacterized.
Objectives
We investigated the clinico‐histopathologic features in relation to OPN3 expression of acral lentiginous melanoma (ALM), which is a rare cutaneous melanoma subtype and not associated with prior sunlight exposure.
Methods
In all, 84 samples of junctional melanocytic nevi (JMN, n = 12), primary ALMs (n = 39) and inguinal lymph node metastasis (ILNM, n = 23) from ALMs were evaluated for the immunohistochemical expression of OPN3. OPN3 messenger RNA and protein level were further determined in melanocytic tumors using quantitative real‐time PCR, multiimmunofluorescence and Western blot assays. We also estimated the associations OPN3 expression between clinicopathological features and prognosis.
Results
ILNMs, in contrast to JMN and ALMs, had higher OPN3 expression scores (p < .001) by immunohistochemistry analysis. High OPN3 score was associated with presence of ulceration, increased Breslow depth and Clark level (p = .025, p = .042, and p = .012, respectively). Furthermore, a remarkable difference (p = .037) of patient overall survival was found when comparing the OPN3 expression of immunohistochemical score between equal to or larger than 100 and below 100 groups. Also, Cox regression models showed that high OPN3 scores were associated with worse melanoma survival.
Conclusion
High OPN3 expression is significantly associated with ALMs and metastatic phenotype as well as a poor prognosis.
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