Actinin-4 Protein Overexpression as a Predictive Biomarker in Adjuvant Chemotherapy for Resected Lung Adenocarcinoma

Abstract

Aim:Although several clinical trials demonstrated the benefits of platinum-combination adjuvant chemotherapy for stage II-IIIA lung adenocarcinoma, predictive biomarkers for the efficacy of such therapy have not yet been identified. We evaluated protein overexpression of actinin-4 as a predictive biomarker of the efficacy of adjuvant chemotherapy in resected lung adenocarcinoma. Materials & methods: We measured actinin-4 protein levels in patients with completely resected stage II-IIIA lung adenocarcinoma using immunohistochemistry and then retrospectively compared survival between adjuvant chemotherapy and observation groups. Results: A total of 148 eligible patients were classified into actinin-4 positive or negative cases by immunohistochemistry. In the former, patients with adjuvant chemotherapy survived significantly longer than those with observation (hazard ratio [HR]: 0.307; p = 0.028). But, no significant survival benefit was noted with adjuvant chemotherapy (HR: 0.926; p = 0.876) in the latter. Conclusion: This marker could predict the efficacy of adjuvant chemotherapy for resected lung adenocarcinoma patients. Non-small-cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. Surgical resection is the most potentially curative treatment and is the standard treatment choice for patients with early stage NSCLC. However, despite curative surgery, the 5-year survival of NSCLC patients is 46-64% at stage IIA, about 36-49% at stage IIB and just 25% at stage IIIA [1,2]. Several meta-analyses and randomized controlled trials, including the JBR.10 and ANITA trials, have demonstrated the efficacy of adjuvant chemotherapy for NSCLC patients [3][4][5][6]. Although adjuvant cisplatin-based chemotherapy is recommended as standard care in completely resected NSCLC patients with stage II-IIIA [7,8], the relative reduction in the risk of death of patients undergoing adjuvant chemotherapy is modest in comparison with that of patients without adjuvant chemotherapy (hazard ratio [HR] for stage II: 0.83; 95% CI: 0.73-0.95; and HR for stage III: 0.83; 95% CI: 0.72-0.94). Therefore, the identification of predictive biomarkers for the efficacy of adjuvant chemotherapy for stage II-IIIA is required in the clinical setting. To identify companion diagnostic biomarkers for adjuvant chemotherapy, numerous prognostic factors as well as predictive factors for adjuvant chemotherapy have been investigated for early stage NSCLC [9][10][11][12][13][14].

Integrated analysis of lncRNAs and mRNAs reveals key trans-target genes associated with ETEC-F4ac adhesion phenotype in porcine small intestine epithelial cells

“…Similarly, actinin alpha 4 ( ACTN4) ubiquitous expression in the kidney is also reported in this study to be up-regulated in adhesive small intestine epithelial cells. This is coherent with many studies that reported the overexpression of ACTN4 in diverse biological conditions including diseases (such as cancers) compared to normal controls [ 22 – 24 ].…”

Role of ACTN4 in Tumorigenesis, Metastasis, and EMT

“…Taking into account the experimental data, the authors proposed that the therapy might impair metastatic activity of cancer cells with high ACTN4 expression. This notion was further supported by the following IHC study of lung adenocarcinoma patients after resection of the primary tumor [24]. The results also highlighted the possibility that the patients may benefit from therapy only when tumors exhibit high ACTN4 expression levels.…”

Actinin-4 as a Diagnostic Biomarker in Serum of Breast Cancer Patients

“…Okamoto et al showed that ACTN4 is expressed in small-cell lung cancer (NSCLC) and is obviously related to distant metastasis [16]. Miura et al found that ACTN4 is a promising predictive indicator for the efficacy of adjuvant chemotherapy in NSCLC [17]. In salivary gland carcinoma, ACTN4 expression level was increased and might be a contribute to the poor overall survival of patients [18].…”

“…The actinin-4 protein level is closely related to the poor prognosis in human cancers, such as thyroid cancer [13], lung cancer [14,15], and salivary gland carcinoma [16]. Additionally, in lung adenocarcinoma, immunohistochemistry showed that actinin-4 protein is overexpressed and can predict the efficacy of adjuvant chemotherapy for resection [17]. However, the expression of ACTN4 and its clinical outcome in BC has not yet been investigated.…”