Treatment and outcomes of melanoma in Asia: Results from the National Cancer Centre Singapore

Teh, Yi Lin; Goh, Wei Lin; Tan, Sze Huey; Yong, Grace; Sairi, A.; Soo, Khee Chee; Ong, Chin-Ann Johnny; Chia, Claramae Shulyn; Tan, Grace Hwei Ching; Soeharno, Henry; Tan, Mann Hong; Chan, Michelle Mei Fung; Selvarajan, Sathiyamoorthy; Sittampalam, Kesavan; Teh, Jonathan; Chin, Francis; Sethi, Vijay; Teo, Melissa Ching Ching; Quek, Richard; Farid, Mohamad

doi:10.1111/ajco.12802

Cited by 18 publications

(11 citation statements)

References 21 publications

(22 reference statements)

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“…Recently study has revealed high expression levels of IL22 in both lung tumors and serum of patients with lung cancer, promoteing Kras mutant lung tumorigenesis 20 . Cutaneous melanoma is obviously different from ocular melanoma and mucosal melanoma in epidemiological features, clinical characteristics, treatment and outcomes 29,30 . Although the direct impact and molecular mechanisms of interleukin 22 on human malignancies had been extensively investigated in a great number of previous studies, few report aim at the direct role of interleukin 22 on cutaneous melanoma.…”

Section: Discussionmentioning

confidence: 99%

IL22 drives cutaneous melanoma cell proliferation, migration and invasion through activation of miR-181/STAT3/AKT axis

He¹,

Yang²,

Xu³

et al. 2020

J. Cancer

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Cutaneous melanoma (CM) is neoplastic growth of melanocytes with strong potential to proliferate and invade, prone to a fatal disease soon which is beyond surgical clearance. The use of regulator involving in antitumor immune responses has been identified as a potential therapeutic option for CM, but still need fully understood at present. Recently, interleukin 22 (IL22), an immune molecule secreted mostly by CD4 + T cells, was reported having functions in a variety of human diseases including encouragement of lung cancer progression, yet, its role in CM is lacking. Here, we first found elevated expression of IL22 in both serum of CM patients and tissues. Up-regulated IL22 significantly promoted cell proliferation, migration and invasion in CM cells deriving from different original culture history. Moreover, in vivo CM model, IL22 treatment caused a significant increase in tumor size. Additionally, we found these effects accompanied by obvious increased miR-181 expression in CM. Importantly, both in vivo and in vitro results revealed that miR-181 downregulation reversed the effects of IL22 on CM cell proliferation, migration, invasion, and CM tumor size as well. Finally, in CM cells deriving from different culture history, we identified STAT3 to be a target gene of miR-181. Higher expression level of IL22 suppressed STAT3 expression, while enhanced expression of p-AKT, p-β-catenin and MMP4; however, down-regulation of miR-181 reversed these situations. Thus, we conclude that IL22 promotes CM progression by driving miR-181/STAT3/AKT axis.

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Section: Discussionmentioning

confidence: 99%

IL22 drives cutaneous melanoma cell proliferation, migration and invasion through activation of miR-181/STAT3/AKT axis

He¹,

Yang²,

Xu³

et al. 2020

J. Cancer

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“…[1][2][3] However, these previous studies comprised mainly white populations, in which SSM and LMM are the major clinical types of melanoma. 4 In contrast, Asians manifest a distinct clinicopathological type of melanoma from that of whites and show much higher frequencies of ALM and MUC, [4][5][6][7] which have been shown to be less susceptible to immune checkpoint inhibitors. 8 Although aPD-1mAb and ipilimumab have demonstrated their efficacy in single-arm studies, 9,10 no comparative studies have been published showing improvement of OS by immune checkpoint inhibitors in Asian melanoma patients.…”

Section: Case Reportmentioning

confidence: 99%

Use of immune checkpoint inhibitors prolonged overall survival in a Japanese population of advanced malignant melanoma patients: Retrospective single institutional study

Nakamura

Fujisawa

Tanaka

et al. 2018

The Journal of Dermatology

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Although recent clinical trials have revealed that immune checkpoint inhibitors significantly improved the overall survival (OS) of patients with advanced melanoma, these previous studies comprised mainly white populations, in which superficial spreading melanoma (SSM) and lentigo maligna melanoma are the major clinical types of melanoma. In contrast, Asians manifest a distinct clinicopathological type of melanoma from that of whites and show much higher frequencies of acral lentiginous melanoma (ALM) and mucosal melanoma, which have been shown to be less susceptible to immune checkpoint inhibitors. Because no comparative studies have been published showing improvement of OS by immune checkpoint inhibitors in Asian melanoma patients, we retrospectively collected the data for 45 melanoma patients treated with checkpoint inhibitors and 24 melanoma patients treated with chemotherapy alone before immune checkpoint inhibitors became available, and compared their OS. The results showed that the patients treated with immune checkpoint inhibitors had significantly better OS than did those treated with chemotherapy alone (P < 0.0001). Improved OS was observed in both the SSM and the ALM patients. In addition, multivariate Cox regression analyses revealed that use of immune checkpoint inhibitors was associated with favorable prognosis (P = 0.0001), indicating that use of immune checkpoint inhibitors is an independent factor for favorable survival. Our study showed that immune checkpoint inhibitors may also improve the prognosis of Asian melanoma patients.

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“…Ocular melanomas are a group of uncommon cancers 1 , and account for approximately 5% of melanoma cases 2 . More than three-quarters of ocular melanomas involve the uvea, with the remainder of cases arising from the conjunctiva 3 . Uveal melanomas (UM) can arise from any part of the uveal tract, including the choroid, iris and ciliary body.…”

Section: Introductionmentioning

confidence: 99%

Clinical features and survival outcomes of ocular melanoma in a multi-ethnic Asian cohort

Tan

Hong

Goh

et al. 2020

Sci Rep

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Ocular melanomas are uncommon cancers in Southeast Asia unlike in the West. We conducted a retrospective review of patients (n = 44) with histologically-proven ocular melanoma within a multi-ethnic Asian cohort from Singapore. Clinicopathological features and relapse patterns were examined, and survival outcomes of interest included recurrence-free survival (RFS) and overall survival (OS). Survival analysis was performed using the Kaplan–Meier method and multivariable Cox proportional regression. The study cohort included 18 male and 26 female patients, with a median age of 52 years (range 8–78). Median follow-up was 154 months. For uveal melanomas (n = 29), the 5-year RFS and OS was 56.8% and 76.6%, respectively; whilst for conjunctival melanomas (n = 15), the 5-year RFS and OS was 30.1% and 68.8%, respectively. Fifteen patients (38.5%) eventually developed metastasis, following which the median survival was only 17 months. Multivariate analysis demonstrated that higher T stage was a significant independent predictor for both OS (HR 8.69, 95% CI 1.03 to 73.09, p = 0.047) and RFS (HR 11.62, 95% CI 2.45 to 55.00, p = 0.002). Smoking history was independently predictive of better RFS (HR 0.08, 95% CI 0.01 to 0.78, p = 0.030). In conclusion, our study demonstrates the poor ocular melanoma outcomes in Southeast Asians, highlighting the necessity for urgent research in this area of unmet clinical need.

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Treatment and outcomes of melanoma in Asia: Results from the National Cancer Centre Singapore

Abstract: Our study reinforces the known unique clinicopathologic features of melanomas in Asians where AM and MM predominate. Age and stage remain the most critical prognostic factors across all subtypes.

Cited by 18 publications

References 21 publications

IL22 drives cutaneous melanoma cell proliferation, migration and invasion through activation of miR-181/STAT3/AKT axis

IL22 drives cutaneous melanoma cell proliferation, migration and invasion through activation of miR-181/STAT3/AKT axis

Use of immune checkpoint inhibitors prolonged overall survival in a Japanese population of advanced malignant melanoma patients: Retrospective single institutional study

Clinical features and survival outcomes of ocular melanoma in a multi-ethnic Asian cohort

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