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pmid:33746582

Granzyme family acts as a predict biomarker in cutaneous melanoma and indicates more benefit from anti-PD-1 immunotherapy.

Xia Wu · Xiaojie Wang · Yan Zhao · Kun Li · Bo Yu · Jianzhong Zhang

International journal of medical sciences · 2021 doi:10.7150/ijms.54747

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Experiment

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Data

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Analysis

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title
Granzyme family acts as a predict biomarker in cutaneous melanoma and indicates more benefit from anti-PD-1 immunotherapy.
doi
10.7150/ijms.54747
pmid
33746582
authors array · 6 items
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Xia Wu
[1]
Xiaojie Wang
[2]
Yan Zhao
[3]
Kun Li
[4]
Bo Yu
[5]
Jianzhong Zhang
journal
International journal of medical sciences
year
2021
abstract
The incidence of cutaneous melanoma (CM) increased since the 1970s, and also along with an unfavorable prognosis. CM patients have been verified benefits from immunotherapy, and granzymes (GZMs) comprise more than 90% of the cytolytic granules secreted by cytotoxic T lymphocytes and nature killer cell. Therefore, it is essential to evaluate the prognostic value of GZMs in CM. A total of 633 CM patients was enrolled to access the prognostic value of GZMs. The integrated prognostic value of five GZMs was validated in TCGA-SKCM, GSE65904, GSE53118, GSE19234 and GSE22153 cohorts. GZMscore, age, Breslow's depth and tumor stage are the independent risk factors for CM patients, risk score based on these factors was calculated in TCGA-SKCM and GSE65906 cohorts, which could polarize the CM patients to high- and low-risk groups with diverse prognosis. Patients in low-risk group obtained the activated immune signaling pathways and response, especially for the activated CD8+ T cells, and could benefit more from anti-PD-1 therapy. A higher tumor mutation burden was observed in low-risk group, especially for the mutation of BRAF. The protect function of GZMK was confirmed by CM cell lines, overexpression of GZMK in A375 and G361 cells suppresses cell proliferation, migration, but not cell apoptosis. All in all, we revealed the prognostic value of GZMs in CM patients, which could also act as a predicted value for the selection of responders of anti-PD-1 immunotherapy.
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K-M survival analysis was used to indicate the different clinical outcomes of subgroups with the 'survminer' package, univariate Cox regression analysis was employed to calculate the hazard ration (HR) and 95% confidence interval (95%CI).
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CM patients have been verified benefits from immunotherapy, and granzymes (GZMs) comprise more than 90% of the cytolytic granules secreted by cytotoxic T lymphocytes and nature killer cell. Therefore, it is essential to evaluate the prognostic value of GZMs in CM. A total of 633 CM patients was enrolled to access the prognostic value of GZMs. The integrated prognostic value of five GZMs was validated in TCGA-SKCM, GSE65904, GSE53118, GSE19234 and GSE22153 cohorts. GZMscore, age, Breslow's depth and tumor stage are the independent risk factors for CM patients, risk score based on these factors was calculated in TCGA-SKCM and GSE65906 cohorts, which could polarize the CM patients to high- and low-risk groups with diverse prognosis. Patients in low-risk group obtained the activated immune signaling pathways and response, especially for the activated CD8+ T cells, and could benefit more from anti-PD-1 therapy. 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