The role of ERBB4 mutations in the prognosis of advanced non-small cell lung cancer treated with immune checkpoint inhibitors

Abstract

Background Immune checkpoint inhibitors (ICIs) have witnessed the achievements of convincing clinical benefits that feature the significantly prolonged overall survival (OS) of patients suffering from advanced non-small cell lung cancer (NSCLC), according to reports recently. Sensitivity to immunotherapy is related to several biomarkers, such as PD-L1 expression, TMB level, MSI-H and MMR. However, a further investigation into the novel biomarkers of the prognosis on ICIs treatment is required. In addition, there is an urgent demand for the establishment of a systematic hazard model to assess the efficacy of ICIs therapy for advanced NSCLC patients. Methods In this study, the gene mutation and clinical data of NSCLC patients was obtained from the TCGA database, followed by the analysis of the detailed clinical information and mutational data relating to two advanced NSCLC cohorts receiving the ICIs treatment from the cBioPortal of Cancer Genomics. The Kaplan–Meier plot method was used to perform survival analyses, while selected variables were adopted to develop a systematic nomogram. The prognostic significance of ERBB4 in pan-cancer was analyzed by another cohort from the cBioPortal of Cancer Genomics. Results The mutation frequencies of TP53 and ERBB4 were 54% and 8% in NSCLC, respectively. The mutual exclusive analysis in cBioPortal has indicated that ERBB4 does show co-occurencing mutations with TP53. Patients with ERBB4 mutations were confirmed to have better prognosis for ICIs treatment, compared to those seeing ERBB4 wild type (PFS: exact p = 0.017; OS: exact p < 0.01) and only TP53 mutations (OS: p = 0.021). The mutation status of ERBB4 and TP53 was tightly linked to DCB of ICIs treatment, PD-L1 expression, TMB value, and TIICs. Finally, a novel nomogram was built to evaluate the efficacy of ICIs therapy. Conclusion ERBB4 mutations could serve as a predictive biomarker for the prognosis of ICIs treatment. The systematic nomogram was proven to have the great potential for evaluating the efficacy of ICIs therapy for advanced NSCLC patients.

Differential microRNA expression for diagnosis and prognosis of papillary thyroid cancer

“…In another study, Wang et al showed that overexpression of miR-551b, a regulator of the gene ERBB4 , may predict poor prognosis in patients with PTC ( 36 ). For instance, ERBB4 could be downregulated in thyroid tumors; hence, this miRNA could be considered a novel biomarker ( 49 ).…”

Mutational variant allele frequency profile as a biomarker of response to immune checkpoint blockade in non-small cell lung Cancer

“…The majority of gene alterations implicated in our model, including PTPRT , EPHA3 , ERBB4 , ATRX , PTPRD , AMER1 , TERT , HGF , POLE , NTRK3 , EPHA5 , ALK , and PGR , were positively correlated with the high-score group and favorable ICI responses. For some of these genes, like PTPRT [ 37 , 38 ], PTPRD [ 38 ], ERBB4 [ 39 ], ATRX [ 40 ], TERT [ 41 ], POLE [ 8 ], NTRK3 [ 42 ], EPHA5 [ 43 ], and ALK [ 14 ], previous literature has highlighted their potential roles as biomarkers for ICIs therapy in NSCLC. Our study firstly reported the significance of EPHA3 , AMER1 , HGF , and PGR alterations.…”

PTPRD mutation is a prognostic biomarker for sensitivity to ICIs treatment in advanced non-small cell lung cancer

“…Sun et al found that ARID1A mutation could serve as predictive biomarkers for the prognosis of ICIs [ 28 ]. Besides that, some studies show ERBB4 mutation and FGFR4 mutation could serve as a potential biomarker for the prognosis of NSCLC with ICIs treatment [ 29 , 30 ]. With the increasing routine of NGS in clinical practice, it is essential to explore predictors factors of response to immunotherapy.…”