Despite optimal and early surgical treatment of non–small-cell lung cancer (NSCLC), many patients die of recurrent NSCLC. We investigated the association between gene methylation and recurrence of the tumor. Fifty-one patients with stage I NSCLC who underwent curative resection but who had a recurrence within 40 months after resection (case patients) were matched on the basis of age, NSCLC stage, sex, and date of surgery to 116 patients with stage I NSCLC who underwent curative resection but who did not have a recurrence within 40 months after resection (controls). We investigated whether the methylation of seven genes in tumor and lymph nodes was associated with tumor recurrence. In a multivariate model, promoter methylation of the cyclin-dependent kinase inhibitor 2A gene p16, the H-cadherin gene CDH13, the Ras association domain family 1 gene RASSF1A, and the adenomatous polyposis coli gene APC in tumors and in histologically tumor-negative lymph nodes was associated with tumor recurrence, independently of NSCLC stage, age, sex, race, smoking history, and histologic characteristics of the tumor. Methylation of the promoter regions of p16 and CDH13 in both tumor and mediastinal lymph nodes was associated with an odds ratio of recurrent cancer of 15.50 in the original cohort and an odds ratio of 25.25 when the original cohort was combined with an independent validation cohort of 20 patients with stage I NSCLC. Methylation of the promoter region of the four genes in patients with stage I NSCLC treated with curative intent by means of surgery is associated with early recurrence.

Objective: Lung cancer is more common in HIV-infected patients than in the general population. We examined how effectively lung cancer was being diagnosed in our HIV-infected patients. Methods: Retrospective study assessing clinical diagnosis of lung cancer in HIV-infected patients at Johns Hopkins Hospital between 1986 and 2004. Results: Ninety-two patients were identified. Compared to HIV-indeterminate patients (n = 4973), HIV-infected individuals were younger with more advanced cancer. CD4 counts and HIV-1 RNA levels indicated preserved immune function. Mortality was higher in HIV-infected patients, with 92% dying of lung cancer (hazard ratio, 1.57; 95% confidence interval, 1.25-1.96), compared to HIV-uninfected patients. Advanced stage and black race were associated with worse survival. After adjustment for these factors, HIV infection was not associated with increased mortality (hazard ratio, 1.04; 95% confidence interval, 0.83-1.32). Of 32 patients followed in our HIV clinic, 60% of chest radiographs had no evidence of neoplasm within 1 year of diagnosis compared to only 1 (4%) of 28 chest computed tomography scans. Nonspecific infiltrates were observed in 9 patients in the same area that cancer was subsequently diagnosed. Conclusions: HIV-infected lung cancer patients have shortened survival mainly due to advanced stage. Low clinical suspicion and overreliance on chest radiographs hindered earlier detection. Aggressive follow-up of nonspecific pulmonary infiltrates in these patients is warranted.

Colorectal cancer (CRC) is one of the common malignant tumors worldwide. Both genetic and epigenetic changes are regarded as important factors of colorectal carcinogenesis. Loss of DACH1 expression was found in breast, prostate, and endometrial cancer. To analyze the regulation and function of DACH1 in CRC, 5 colorectal cancer cell lines, 8 cases of normal mucosa, 15 cases of polyps and 100 cases of primary CRC were employed in this study. In CRC cell lines, loss of DACH1 expression was correlated with promoter region hypermethylation, and re-expression of DACH1 was induced by 5-Aza-2'-deoxyazacytidine treatment. We found that DACH1 was frequently methylated in primary CRC and this methylation was associated with reduction in DACH1 expression. These results suggest that DACH1 expression is regulated by promoter region hypermethylation in CRC. DACH1 methylation was associated with late tumor stage, poor differentiation, and lymph node metastasis. Re-expression of DACH1 reduced TCF/LEF luciferase reporter activity and inhibited the expression of Wnt signaling downstream targets (c-Myc and cyclinD1). In xenografts of HCT116 cells in which DACH1 was re-expressed, tumor size was smaller than in controls. In addition, restoration of DACH1 expression induced G2/M phase arrest and sensitized HCT116 cells to docetaxel. DACH1 suppresses CRC growth by inhibiting Wnt signaling both in vitro and in vivo. Silencing of DACH1 expression caused resistance of CRC cells to docetaxel. In conclusion, DACH1 is frequently methylated in human CRC and methylation of DACH1 may serve as detective and prognostic marker in CRC.