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Integrin ?11 in non-small cell lung cancer is associated with tumor progression and postoperative recurrence.

ABSTRACT: Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin ?11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin ?11?1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non-small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT-PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence-free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.

SUBMITTER: Ando T

PROVIDER: S-EPMC6942423 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Integrin α11 in non-small cell lung cancer is associated with tumor progression and postoperative recurrence.

Ando Takahiro T Kage Hidenori H Matsumoto Yoko Y Zokumasu Koichi K Yotsumoto Takuma T Maemura Keita K Amano Yosuke Y Watanabe Kousuke K Nakajima Jun J Nagase Takahide T Takai Daiya D

Cancer science 20191218 1

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non-small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT-PCR in 80 sam ...[more]

PMID: 31778288

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Project description:Background: The clinical value and delineation of clinical target volume (CTV) of postoperative radiotherapy (PORT) in completely resected (y)pN2 non-small cell lung cancer (NSCLC) remain controversial. Investigations specifically focusing on the cumulative incidence and prognostic significance of initial disease recurrence at the supraclavicular region (SCR) in this disease population are seldom reported. Methods: Consecutive patients with curatively resected (y)pN2 NSCLC who received adjuvant chemotherapy from January 2013 to December 2018 at our cancer center were retrospectively examined. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was defined as loco-regional recurrence (LRR). Disease recurrence beyond LRR and SCR, was defined as distant metastasis (DM). Overall survival (OS1 and OS2) were calculated from surgery and disease recurrence to death of any cause, in the entire cohort and in patients with recurrent disease, respectively. Results: Among the 311 patients enrolled, PORT without elective supraclavicular nodal irradiation (ESRT) was performed in 94 patients and neoadjuvant chemotherapy was administered in 31 patients. With a median follow-up of 26 months, 203 patients developed recurrent disease, including 27 SCRs, among which 16 were without DM and 22 involved the ipsilateral supraclavicular region. The 1, 3, and 5-year cumulative incidence of SCR were 6.53, 13.0, and 24.7%, respectively. Chosen DM as a competing event, cN2, ypN2, not receiving lobectomy, and negative expression of CK7 were significantly associated with SCR using the univariate competing risk analysis, while ypN2 was identified as the only independent risk factor of SCR (p = 0.012). PORT significantly reduced LRR (p = 0.031) and prolonged OS1 (p = 0.018), but didn't impact SCR (p = 0.254). Pattern of failure analyses indicated that the majority of LRRs developed within the actuarial or virtual CTV of PORT, and 15 of the 22 ipsilateral SCRs could be covered by the virtual CTV of proposed ESRT. In terms of OS2, patients who developed SCR but without DM had intermediate prognosis, compared with those who had DM (p = 0.009) and those who had only LRR (p = 0.048). Conclusions: SCR is not uncommon and has important prognostic significance in completely resected (y)pN2 NSCLC. The clinical value of PORT and ESRT in such patients need to be further investigated.

Project description:BACKGROUND:The role of postoperative radiotherapy (PORT) in the treatment of patients with completely resected non-small cell lung cancer (NSCLC) was not clear. A systematic review and individual participant data meta-analysis was undertaken to evaluate available evidence from randomised controlled trials (RCTs). These results were first published in Lung Cancer in 2013. OBJECTIVES:To evaluate the effects of PORT on survival and recurrence in patients with completely resected NSCLC. To investigate whether predefined patient subgroups benefit more or less from PORT. SEARCH METHODS:We supplemented MEDLINE and CANCERLIT searches (1965 to 8 July 2016) with information from trial registers, handsearching of relevant meeting proceedings and discussion with trialists and organisations. SELECTION CRITERIA:We included trials of surgery versus surgery plus radiotherapy, provided they randomised participants with NSCLC using a method that precluded prior knowledge of treatment assignment. DATA COLLECTION AND ANALYSIS:We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. We sought data on all participants from those responsible for the trial. We obtained updated individual participant data (IPD) on survival and date of last follow-up, as well as details on treatment allocation, date of randomisation, age, sex, histological cell type, stage, nodal status and performance status. To avoid potential bias, we requested information on all randomised participants, including those excluded from investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. MAIN RESULTS:We identified 14 trials evaluating surgery versus surgery plus radiotherapy. Individual participant data were available for 11 of these trials, and our analyses are based on 2343 participants (1511 deaths). Results show a significant adverse effect of PORT on survival, with a hazard ratio of 1.18, or an 18% relative increase in risk of death. This is equivalent to an absolute detriment of 5% at two years (95% confidence interval (CI) 2% to 9%), reducing overall survival from 58% to 53%. Subgroup analyses showed no differences in effects of PORT by any participant subgroup covariate.We did not undertake analysis of the effects of PORT on quality of life and adverse events. Investigators did not routinely collect quality of life information during these trials, and it was unlikely that any benefit of PORT would offset the observed survival disadvantage. We considered risk of bias in the included trials to be low. AUTHORS' CONCLUSIONS:Results from 11 trials and 2343 participants show that PORT is detrimental to those with completely resected non-small cell lung cancer and should not be used in the routine treatment of such patients. Results of ongoing RCTs will clarify the effects of modern radiotherapy in patients with N2 tumours.

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Integrin ?11 in non-small cell lung cancer is associated with tumor progression and postoperative recurrence.

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Integrin α11 in non-small cell lung cancer is associated with tumor progression and postoperative recurrence.

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