Long non-coding RNAs (lncRNAs) are a kind of RNAs with regulation that participate fundamental cellular processes via diverse mechanisms. Despite the potential importance of lncRNAs in multiple kinds of cancer has been well studied, no comprehensive survey of cancer subtype associated lncRNAs. Here, we performed an array-based transcriptional survey of lncRNAs across 150 lung cancer samples comprising both adenocarcinoma and squamous cell carcinoma, and 306 breast cancer patients with clear clinical information. In lung cancer, 72 lncRNAs are identified to be associated with tumor subtypes and their functions as well as the associated proteins are predicted by constructing coding-non-coding co-expression network. The results suggest that they are mostly related with epidermis development, cell adhesion and response to stimulus. The validation results show the high concordance and confirmed the robust of the identification results. In breast cancer, we found 3 lncRNA genes are associated with estrogen receptor [agr] (ER) positive and ER negative subtypes and tumor histologic grade. Survival (Kaplan-Meier) analysis results suggest that the expression pattern of the 3 lncRNAs is significantly correlated with clinical outcomes. The current study provides the first large-scale survey of lncRNAs within cancer subtypes, and may offer new targets for their diagnosis, therapy and prognosis.

Immune checkpoint blockade‐related pneumonitis is a rare but potentially life‐threatening adverse effect, but its risk factors are not completely understood. This case‐control study was conducted to identify pneumonitis risk factors in patients treated with anti‐PD1 monoclonal antibodies (mAbs), including all the patients who developed pneumonitis after anti‐PD‐1 mAbs treatment in the Cancer Center of the Chinese People's Liberation Army from September 2015 to September 2017. Two controls per case were matched according to a propensity‐score matching algorithm to account for confounding effects caused by individual baseline variables. Demographic and clinical information was obtained from medical records. In total, 55 cases and 110 controls were included in the study. No association was observed between smoking status or primary lung cancer and risk of pneumonitis. Significant risk factors for pneumonitis related to anti‐PD‐1 mAbs were prior thoracic radiotherapy, prior lung disease and combination therapy with odds ratios of 3.34 (1.51‐7.39), 2.86 (1.45‐5.64) and 2.73 (1.40‐5.31), respectively. The associations remained significant in the multivariable logistic regression model. The risk of pneumonitis induced by anti‐PD‐1 mAbs is associated with prior thoracic radiotherapy, prior lung disease, and combination therapy. Clinicians should monitor these features in patients receiving anti‐PD‐1 therapy to optimize clinical safety and efficacy.

To examine the relationship between cytotoxic T lymphocyte antigen 4 (CTLA-4) expression and breast cancer prognosis, CTLA-4 expression was immunohistochemically detected in paraffin-embedded specimens of primary tumors from 130 patients with breast cancer who had a mean follow-up period of 112 months. CTLA-4 expressed in cytoplasm of breast cancer cells and in cytoplasm and cell membranes of interstitial lymphocytes. Univariate analysis (log-rank) associated higher density of interstitial CTLA-4⁺ lymphocytes with longer DFS and OS, but higher tumor CTLA-4 expression with shorter OS. After controlling for age, clinical stage, Scarff-Bloom-Richardson grade, tumor thrombus, ER, PR, HER2 and Ki-67, multivariate analysis (Cox) showed that density of interstitial CTLA-4⁺ lymphocytes independently predicted longer DFS (HR 0.315, P = 0.002) and OS (HR 0.313, P = 0.005), whereas tumor CTLA-4 expression independently predicted shorter DFS (HR 2.176, P = 0.029) and OS (HR 2.820, P = 0.007), i.e., patients with high CTLA-4⁺ lymphocyte density and CTLA-4^low tumor cells had the best prognoses. These results indicated that CTLA-4 expression in lymphocytes was associated with better prognosis, but that in tumor cells was associated with worse prognosis. Patients’ CTLA-4 profiles might thus be used to predict the benefits and toxicity of CTLA-4 blockade.

Background The V325 study showed that docetaxel, cisplatin, and fluorouracil (DCF) prolonged overall survival (OS) of patients with advanced gastric cancer, but with a high incidence of dose-limiting toxicities. We investigated the efficacy and safety of a modified DCF (mDCF) regimen for Chinese patients with advanced gastric cancer. Methods Untreated advanced gastric cancer patients randomly received docetaxel and cisplatin at 60 mg/m² (day 1) followed by fluorouracil at 600 mg/m²/day (days 1–5; mDCF regimen) or cisplatin at 75 mg/m² (day 1) followed by fluorouracil at 600 mg/m²/day (days 1–5; CF) every 3 weeks. The primary end point was progression-free survival (PFS). The secondary end points were OS, overall response rate (ORR), time-to-treatment failure (TTF), and safety. Results In total, 243 patients were randomized to treatment (mDCF regimen 121; CF 122). Compared with CF, the mDCF regimen significantly improved PFS and OS: the median PFS was 7.2 and 4.9 months, respectively [hazard ratio (HR) 0.58, log-rank P = 0.0008], and the median OS was 10.2 and 8.5 months, respectively (HR = 0.71, P = 0.0319). Additionally, the mDCF regimen improved the parameters used as secondary objectives: the ORR was 48.7 % with the mDCF regimen versus 33.9 % with CF (P = 0.0244); the median TTF was 3.4 months with the mDCF regimen and 2.4 months with CF (HR = 0.67, P = 0.0027). Grade 3 and grade 4 treatment-related adverse events occurred in 77.3 % of patients who received the mDCF regimen versus 46.1 % of patients who received CF (P < 0.001). Conclusions The mDCF regimen, compared with CF, significantly prolonged PFS and OS and enhanced ORR of Chinese patients with advanced gastric cancer. The mDCF regimen achieved efficacy comparable to that of DCF but with fewer toxicities, which is appropriate for the Chinese population.

While chemotherapy significantly improves the prognosis of breast cancer patients, it also damages otherwise healthy organs, such as the ovaries. Gonadotropin-releasing hormone (GnRH) agonists may have a protective effect against chemotherapy-induced ovarian toxicity in premenopausal women being treated for breast cancer; however, studies of its clinical efficacy have reported conflicting results. This meta-analysis was designed to assess the collective data from previous studies of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian toxicity in premenopausal women with breast cancer. Electronic literature databases (Cochrane Library, Medline, and Embase) were searched for relevant randomized controlled trials (RCTs) published prior to April 2012. Only RCTs that compared GnRH agonists plus chemotherapy to chemotherapy alone for premenopausal women with breast cancer were selected. A random-effects model was used to calculate the risk ratios (RRs) for premature ovarian failure (POF) within one year after chemotherapy treatment and rates of resumed menses and spontaneous pregnancy during the follow-up period after cessation of treatment. Five RCTs composed of 528 patients (GnRH agonist combination, n = 274; chemotherapy alone, n = 254) were included in the meta-analysis. Significantly fewer women treated with GnRH agonist experienced post-chemotherapy POF, yielding a RR of 0.40 (vs. chemotherapy alone, 95% confidence interval [CI] 0.21-0.75). In contrast, both treatment groups experienced similar rates of resumed menses (RR = 1.31, 95% CI 0.93-1.85) and spontaneous pregnancy (RR = 0.96, 95% CI 0.20-4.56). Concurrent administration of GnRH agonists during chemotherapy treatment of breast cancer in premenopausal women appears to protect against chemotherapy-related POF in the first year after treatment, but appears to have no effect on resumed menses or spontaneous pregnancy rates.