RESUMO
Tumor mutation burden (TMB) is an independent indicator used to select patients sensitive to immunotherapy. The present study aimed to investigate the clinicopathological and molecular characteristics of patients with hypermutant lung cancer to identify an economical, simple and complementary method for predicting TMB and immunotherapy responses. In total, 1,000 patients with lung cancer were randomly selected, and their samples were submitted to next-generation sequencing, with their TMB status reviewed. The threshold of hypermutation was set to 17.24 mutations (muts)/Mb. The proportion of smokers was higher in the hypermutant cohort (n=67) compared with in the non-hypermutant cohort (n=933; 85.1 vs. 46.6%; P<0.0001). Compared with in the non-hypermutant cohort, the proportion of squamous cell carcinoma cases and small cell lung cancer cases was higher in the hypermutant cohort (22.4 vs. 13.1% and 6.0 vs. 2.6%, respectively). In addition, compared with in the non-hypermutant cohort, mutations in the low-density lipoprotein receptor-related protein 1B were more frequently observed in the hypermutant cohort (67.2 vs. 14.3%; P<0.0001). A similar trend was obtained for all genes tested, except for the EGFR gene. Furthermore, in the hypermutant cohort, the prevalence of microsatellite instability was extremely high (9.0%). The mutation frequency in DNA damage response (DDR) genes was notably higher in the hypermutant cohort, where several DDR-associated genes were enriched, compared with in the non-hypermutant cohort. The enrichment analysis revealed a strong association between mutations in Notch signaling and high TMB. To the best of our knowledge, the present study is the first to comprehensively investigate the clinical and genetic characteristics of patients with hypermutant lung cancer in a Chinese population. The results of the current study suggested that hypermutant lung cancer exerted distinctive clinical and genetic features, which may be used as complementary indicators for screening patients sensitive to immunotherapy.
RESUMO
Wild-type p53-induced phosphatase 1 (Wip1), also termed PPM1D, is a member of the protein phosphatase 2C family, which is characterized by distinctive oncogenic properties. Overexpression of Wip1 is observed in certain types of human tumors that are associated with significantly poor prognosis. The present study aimed to detect the expression of Wip1 in non-small cell lung cancer (NSCLC) and to analyze its prognostic value in such patients. The protein expression level of Wip1 was compared between NSCLC and normal lung tissue specimens using by immunohistochemistry, and it was found that Wip1 was highly expressed in NSCLCs but was absent or weakly expressed in normal lung tissues. Detailed clinical and demographic information of patients were retrospectively collected pre- and postoperatively, and Kaplan-Meier survival and Cox's regression analyses were performed to evaluate the prognosis of patients. Survival analysis revealed that the overall survival rate for patients in the Wip1-positive expression group was significantly lower than that of the Wip1-negative group, and Cox multivariate analysis indicated that positive Wip1 expression, pN classification and pathological stage were significant prognostic predictors. The results of the current study suggest that Wip1 may be associated with pathological diagnosis and prognostic evaluation of NSCLC.
RESUMO
The present study reports the local recurrence, distant metastasis, progression-free survival, overall survival and radiation toxicity between two arms of stage III non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT); one arm with clinical target volume (CTV) and the other without CTV. The two arms of local recurrence, distant metastasis, progression-free survival, overall survival, grade 3-4 radiation esophagitis and hematological toxicity had no statistical significance. However, the grade 3-4 radiation pneumonia rate of the group without CTV was significantly decreased. This supports the concept that stage III NSCLC treated with IMRT, which omitted CTV, can reduce the occurrence of radiation pneumonia. The aim of the present study was to analyze the feasibility of the smaller target volume for stage III NSCLC treated with IMRT. Data from 105 patients with stage III NSCLC who were hospitalized and received IMRT between January 1, 2008 and November 30, 2012 were retrospectively analyzed. A total of 55 cases were irradiated with target volume without CTV and 50 cases were irradiated with CTV. Dose prescription was 100% PTV at 54-63 Gy/27-35 F/5.4-7 weeks. The two arms of the patient characteristics and treatment deliveries had no statistical significance. The two arms of the patients were compared for local recurrence, distant metastasis, progression-free survival, overall survival and radiation-related toxicity. In the arms without and with CTV, the local relapse and distant metastases rates were 32.7 and 32.0% (P=1.000) and 56.4 and 48.0% (P=0.946), respectively. The median progression-free survival time for the two arms was 9 months (P=0.619). The 1-, 2- and 3-year survival rates of the arms without and with CTV were 74.5, 43.6 and 23.6%, and 70.0, 46.0 and 20.0% (P=0.956), respectively. In the two arms, grade 3-4 radiation esophagitis and hematological toxicity had no statistical significance. However, in the arm without CTV, grade 3-4 radiation pneumonia was only 5.5%, compared with 18.0% in the arm with CTV (P=0.044). In conclusion, the smaller target volume for stage III NSCLC treated with IMRT was feasible.
