Potential prognostic value of PD-L1 and NKG2A expression in Indonesian patients with skin nodular melanoma

Saputro R.D., Rinonce H.T., Iramawasita Y., Ridho M.R., Pudjohartono M.F., Anwar S.L., Setiaji K., Aryandono T.

Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito Hospital, Sleman, Yogyakarta, Indonesia; Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito Hospital, Sleman, Yogyakarta, Indonesia


Abstract

Objective: Biomarker mRNA levels have been suggested to be predictors of patient survival and therapy response in melanoma cases. This study aimed to investigate the correlations between the mRNA expression levels of PD-L1 and NKG2A in melanoma tissue with clinicopathologic characteristics and survival in Indonesian primary nodular melanoma patients. Results: Thirty-one tissue samples were obtained; two were excluded from survival analysis due to Breslow depth of less than 4 mm. The median survival of upregulated and normoregulated PD-L1-patients were 15.800 ± 2.345 and 28.945 ± 4.126 months, respectively. However, this difference was not significant statistically (p = 0.086). Upregulated and normoregulated NKG2A patients differed very little in median survival time (25.943 ± 7.415 vs 26.470 ± 3.854 months; p = 0.981). Expression of PD-L1 and NKG2A were strongly correlated (rs: 0.787, p < 0.001). No clinicopathologic associations with PD-L1 and NKG2A mRNA levels were observed. These results suggest that PD-L1 may have potential as a prognostic factor. Although an unlikely prognostic factor, NKG2A may become an adjunct target for therapy. The strong correlation between PD-L1 and NKG2A suggests that anti-PD-1 and anti-NKG2A agents could be effective in patients with PD-L1 upregulation. The mRNA levels of these two genes may help direct choice of immunotherapy and predict patient outcomes. © 2021, The Author(s).

Indonesia; Melanoma; NKG2A; PD-L1; Skin cancer


Journal

BMC Research Notes

Publisher: BioMed Central Ltd

Volume 14, Issue 1, Art No 206, Page – , Page Count


Journal Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85107072764&doi=10.1186%2fs13104-021-05623-7&partnerID=40&md5=1cf9d810780c557152e850da37164a45

doi: 10.1186/s13104-021-05623-7

Issn: 17560500

Type: All Open Access, Gold, Green


References

(2018) GLOBOCAN Fact Sheet: Melanoma of Skin. Global Cancer Observatory, , http://globocan.iarc.fr/old/bar_sex_site.asp?selection=16120&title=Melanoma+of+skin&statistic=2&populations=6&window=1&grid=1&color1=5&color1e=&color2=4&color2e=&submit=Execute; (2018) Estimated Number of Incident Cases from 2018 to 2040: Melanoma of Skin. Cancer Tomorrow, , https://gco.iarc.fr/tomorrow/graphic-line?type=0&type_sex=0&mode=population&sex=0&populations=900&cancers=16&age_group=value&apc_male=0&apc_female=0&single_unit=500000&print=0; Domingues, B., Lopes, J.M., Soares, P., Pópulo, H., Melanoma treatment in review (2018) ImmunoTargets Ther, 7, pp. 35-49. , COI: 1:CAS:528:DC%2BC1MXhsVejs7vN; Van Hall, T., André, P., Horowitz, A., Ruan, D.F., Borst, L., Zerbib, R., Monalizumab: inhibiting the novel immune checkpoint NKG2A (2019) J Immunother Cancer, 7 (1), p. 263; Abdel-Rahman, O.P.D., PD-L1 expression and outcome of advanced melanoma patients treated with anti-PD-1/PD-L1 agents: a meta-analysis (2016) Immunotherapy, 8 (9), pp. 1081-1089. , COI: 1:CAS:528:DC%2BC28Xht1Krs7%2FF; Yang, J., Dong, M., Shui, Y., Zhang, Y., Zhang, Z., Mi, Y., A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients (2020) Cancer Cell Int, 20 (1), p. 96; Patel, S.P., Kurzrock, R., PD-L1 expression as a predictive biomarker in cancer immunotherapy (2015) Mol Cancer Ther, 14 (4), pp. 847-856. , COI: 1:CAS:528:DC%2BC2MXmtlCitrg%3D; Lee, H.H., Wang, Y.N., Xia, W., Chen, C.H., Rau, K.M., Ye, L., Removal of N-linked glycosylation enhances PD-L1 detection and predicts anti-PD-1/PD-L1 therapeutic efficacy (2019) Cancer Cell Int, 36 (2), pp. 168-178.e4. , COI: 1:CAS:528:DC%2BC1MXhsVWlurrN; Tang, Y., Xie, C., Zhang, Y., Qin, Y., Zhang, W., Overexpression of mRNA-decapping enzyme 1a predicts disease-specific survival in malignant melanoma (2018) Melanoma Res, 28 (1), pp. 30-36. , COI: 1:CAS:528:DC%2BC2sXitVWgurbP; Hoffmann, F., Zarbl, R., Niebel, D., Sirokay, J., Fröhlich, A., Posch, C., Prognostic and predictive value of PD-L2 DNA methylation and mRNA expression in melanoma (2020) Clin Epigenet, 12 (1), p. 94. , COI: 1:CAS:528:DC%2BB3cXhtlWgtbrE; Wan, X., Liu, R., Li, Z., The prognostic value of HRAS mRNA expression in cutaneous melanoma (2017) BioMed Res Int, 2017, p. 5356737. , PID: 29349077; Gupta, S., McCann, L., Chan, Y.G.Y., Lai, E.W., Wei, W., Wong, P.F., Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma (2019) J Immunother Cancer, 7 (1), p. 254; Vassilakopoulou, M., Avgeris, M., Velcheti, V., Kotoula, V., Rampias, T., Chatzopoulos, K., Evaluation of PD-L1 expression and associated tumor-infiltrating lymphocytes in laryngeal squamous cell carcinoma (2016) Clin Cancer Res, 22 (3), pp. 704-713. , COI: 1:CAS:528:DC%2BC28XitFeqs7c%3D; Meckawy, G.R., Mohamed, A.M., Zaki, W.K., Khattab, M.A., Amin, M.M., ElDeeb, M.A., Natural killer NKG2A and NKG2D in patients with colorectal cancer (2019) J Gastrointest Oncol, 10 (2), pp. 218-225; Taube, J.M., Anders, R.A., Young, G.D., Xu, H., Sharma, R., McMiller, T.L., Colocalization of inflammatory response with B7–H1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape (2012) Sci Transl Med., 4 (127), p. 127ra37; Audrito, V., Serra, S., Stingi, A., Orso, F., Gaudino, F., Bologna, C., PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR-17-5p (2017) Oncotarget, 8 (9), pp. 15894-15911; Robert, C., Long, G.V., Brady, B., Dutriaux, C., Di Giacomo, A.M., Mortier, L., Five-year outcomes with nivolumab in patients with wild-type BRAF advanced melanoma (2020) J Clin Oncol., 38 (33), pp. 3937-3946. , COI: 1:CAS:528:DC%2BB3cXisVKls7bN; Obeid, J.M., Erdag, G., Smolkin, M.E., Deacon, D.H., Patterson, J.W., Chen, L., PD-L1, PD-L2 and PD-1 expression in metastatic melanoma: correlation with tumor-infiltrating immune cells and clinical outcome (2016) Oncoimmunology, 5 (11); Massi, D., Brusa, D., Merelli, B., Falcone, C., Xue, G., Carobbio, A., The status of PD-L1 and tumor-infiltrating immune cells predict resistance and poor prognosis in BRAFi-treated melanoma patients harboring mutant BRAFV600 (2015) Ann Oncol, 26 (9), pp. 1980-1987; Badalamenti, G., Fanale, D., Incorvaia, L., Barraco, N., Listì, A., Maragliano, R., Role of tumor-infiltrating lymphocytes in patients with solid tumors: can a drop dig a stone? (2017) Cell Immunol, 2019 (343), p. 103753; Zaghi, E., Calvi, M., Marcenaro, E., Mavilio, D., Di Vito, C., Targeting NKG2A to elucidate natural killer cell ontogenesis and to develop novel immune-therapeutic strategies in cancer therapy (2019) J Leukoc Biol, 105 (6), pp. 1243-1251. , COI: 1:CAS:528:DC%2BC1MXpsFWhug%3D%3D; Borst, L., van der Burg, S.H., van Hall, T., The NKG2A–HLA-E axis as a novel checkpoint in the tumor microenvironment (2020) Clin Cancer Res, 26 (21), pp. 5549-5556. , COI: 1:CAS:528:DC%2BB3cXisVKmt7vP; Lee, H., Quek, C., Silva, I., Tasker, A., Batten, M., Rizos, H., Integrated molecular and immunophenotypic analysis of NK cells in anti-PD-1 treated metastatic melanoma patients (2019) Oncoimmunology, 8 (2); Jayawardana, K., Schramm, S.J., Haydu, L., Thompson, J.F., Scolyer, R.A., Mann, G.J., Determination of prognosis in metastatic melanoma through integration of clinico-pathologic, mutation, mRNA, microRNA, and protein information (2015) Int J Cancer, 136 (4), pp. 863-874. , COI: 1:CAS:528:DC%2BC2cXhtF2rs7%2FI

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