P2.14-06 The Study of Rac3 Molecular Mechanism Through ERK Signaling Pathway in Lung Adenocarcinoma

Abstract

Background: Epidermal growth factor (EGFR) gene mutation status in lung adenocarcinoma has been demonstrated to reflect the therapeutic efficacy of tyrosine kinase inhibitors (TKIs). In this study, we investigated the association of EGFR mutation status with prognostic impact. Method: From January 2010 to December 2018, we retrospectively reviewed 450 patients with resected lung adenocarcinomas who underwent EGFR mutation status analysis. Clinicopathological factors analyzed included age, sex/gender, smoking history, serum carcinoembryonic antigen (CEA) levels, lymphatic invasion (Ly), vascular invasion (V), histological grade, malignant component, pathological stage, and EGFR mutation. Univariate and multivariate analyses of overall survival (OS) and recurrence-free survival (RFS) were conducted. Result: The study group comprised 450 patients (260 men, 190 women; age range: 32e88 years; mean age: 67.6±9.9 years). The median follow-up period was 35.4 months. A total of 282 patients were smokers and 168 were nonsmokers. EGFR mutation analysis identified 186 patients with EGFR mutation and 264 patients with wild-type EGFR. Preoperative CEA was elevated in 117 patients. Ly, V, high grade, high malignant component and advanced stage were observed in 72, 73, 209, 120 and 102 patients, respectively. The 5-year OS in patients with EGFR mutation was 80.6% compared with 75.6% for those with wild-type EGFR (p¼0.011). The 5-year RFS in patients with EGFR mutation status was 77.1% compared with 66.8% for patients with wild-type EGFR (p¼0.036). There were no significant differences in OS and RFS between patients with exon 21 L858R, exon 19 deletion and other mutation subtypes. In addition, there was no survival difference in patients with EGFR mutation who received TKI or not after lung cancer recurrence. In multivariate analysis for OS, EGFR mutation status was an independent significant prognostic factor, as well as age, Ly, and pathological stage. Conclusion: EGFR mutation status is an independent good prognostic factor in patients with resected lung adenocarcinoma regardless of TKI use. EGFR mutation subtypes did not show significant differences in prognosis.

Multiple Omics Analysis of the Rac3 Roles in Different Types of Human Cancer

“…Compared with normal tissues, Rac3 mRNA levels were significantly overexpressed in BLCA, CESC, DLBC, HNSC, LIHC, LUAD, LUSC, OV, PAAD, PRAD, SKCM, THCA, THYM, UCEC, and UCS, while it was underexpressed in KIRC and LAML. The results were further supported by previous studies involving in bladder cancer [10], [11], lung adenocarcinoma [14], [38], breast cancer [39], [40], prostate carcinomas [41], brain tumors [42], colitis-associated cancer [43], and acute myeloid leukemia [44]. Moreover, the protein expression of Rac3 was highly expressed in lung cancer, head and neck cancer, liver cancer, urothelial cancer, breast cancer, cervical cancer, ovarian cancer, lymphoma, and skin cancer from the HPA database.…”

“…Ramos et al revealed that Rac3 levels were increased in AML compared with healthy donors [44]. Rac3 was overexpressed and associated with more prolonged survival in LUAD patients [38], [46]. RAC3 was overexpressed in ERα-positive breast cancers and implied poor recurrence free survival [39].…”

“…Previous research showed that overexpression of RAC3 could activate Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway by PYCR1 to promote proliferation and invasion of BLCA cells [11] and regulate the ERK signaling pathway to promote proliferation and migration of LUAD cells [38]. It controlled the proliferation of breast cancer cells by the Rac3-Pak pathway [53].…”

“…Compared with the existing works, our study not only expanded the understanding of the Rac3 roles in pan cancers but also obtained new meaningful findings. Previous research that investigated differential expression of Rac3 focused on a single type of cancer, such as acute myeloid leukemia [44], bladder cancer [10], colitis-associated cancer [43], and lung Adenocarcinoma [38]. However, Pan-cancer analysis can provide a comprehensive insight into the Rac3 roles.…”