BRAF mutations occur in 2–4% non-small cell lung cancer (NSCLC) patients and can be categorized into three functional classes based on signaling mechanism and kinase activity: RAS-independent kinase-activating V600 monomers (class 1), RAS-independent kinase-activating dimers (class 2) and RAS-dependent kinase-inactivating heterodimers (class 3). The association between functional classes and clinical features in Chinese NSCLC patients remains unexplored. Our multi-center study aimed to survey the BRAF mutation rate and analyze the associated clinical features in this population. Capture-based sequencing data of either plasma or tissue samples obtained from 8405 Chinese stage I–IV NSCLC patients were retrospectively analyzed. BRAF mutations were detected in 238 patients, revealing an overall mutation rate of 2.8%. Among them, 32%, 21% and 13% had BRAF mutant class 1, 2 and 3 respectively. The remaining 34% had other BRAF mutations. V600 (32%) and G469 (13%) were the two most predominant BRAF mutations. Patients with class 2 and 3 mutations were more likely to have concurrent KRAS mutations (P = 0.001). Collectively, BRAF mutations, including non-class 1–3 mutations, were more likely to occur in males (P < 0.01). However, females were more likely to harbor class 1 mutations (P < 0.02). We also compared the overall survival (OS) of first-line chemotherapy-treated advanced-stage patients and revealed comparable OS among the three groups. Our study revealed a 2.8% BRAF mutation rate in Chinese NSCLC patients. Our data also showed a male predominance when all BRAF mutations were considered collectively, and a female predominance for class 1 mutations. Furthermore, BRAF V600E is less likely to have concurrent KRAS mutations comparing to the other two classes.

Background: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. This study was designed to investigate the prognostic values of red blood cell (RBC)-associated indicators, including RBC, hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW) in resectable GC patients. Methods: In this retrospective study, a total of 104 pathologically confirmed GC patients were recruited. These cases were divided into two groups according to the median values of pretreatment RBC, HGB, HCT, MCV, MCH, MCHC, or RDW. To evaluate the changes in RBC-associated indicators values after treatment, we introduced the concept of post-/pre-treatment ratios (≤1 suggested RBC, HGB, HCT, MCV, MCH, MCHC, or RDW values were not increased after therapy, while >1 represented those in increased levels). Results: The lower pretreatment MCHC levels were correlated with worse overall survival (OS), while pretreatment levels of RBC, HGB, HCT, MCV, MCH, or RDW were not. The whole course of treatment (surgery plus adjuvant chemotherapy) significantly decreased the values of MCHC, and increased the values of MCV and RDW, whereas it had no obvious effects on the values of RBC, HGB, HCT, or MCH. Patients with post-/pre-treatment MCV ratio >1 had an increased survival ratio. Meanwhile, post-/pre-treatment RBC, HGB, HCT, MCH, MCHC, or RDW ratios were not correlated with outcomes. Multivariate Cox regression analysis revealed that the American Joint Committee on Cancer (AJCC) stage (III), and lower pretreatment MCHC levels were independent risk factors affecting OS. The receiver operating characteristic (ROC) curve analysis showed that an MCHC value of 341.98 g/L was the optimal cutoff value for prognosis, with a sensitivity of 58.3% and a specificity of 75.0%. Conclusions: Pretreatment MCHC levels could become a potential prognostic factor for resectable GC.

Background: The long non-coding RNA (lncRNA) RP9 pseudogene (RP9P) is a pseudogene-derived lncRNA that has never been reported in cancer, and its function underlying tumorigenesis in colorectal cancer (CRC) remains unknown.Methods: RP9P and miR-133a-3p were filtered through bioinformatics analysis. The level of RP9P, miR-133a-3p, and FOXQ1 in CRC cell lines was detected by real-time PCR. Cell Counting Kit-8 and flow cytometric analyses were used to detect cell proliferation and apoptosis, respectively. Interactions between RP9P, miR-133a-3p, and FOXQ1 were confirmed by a dual-luciferase reporter assay.Results: RP9P was overexpressed in CRC compared to normal control tissues and cells. Knockdown of RP9P inhibited CRC cell viability. RP9P directly interacted with miR-133a-3p, and miR-133a-3p downregulation abrogated the tumor-suppressing effect of RP9P knockdown. miR-133a-3p directly targeted FOXQ, which was positively regulated by RP9P. RP9P knockdown decreased FOXQ1 expression levels in CRC cells by directly targeting miR-133a-3p via a sponge mechanism. In addition, in vivo experiments in a xenograft model revealed that downregulated RP9P expression inhibited CRC cell tumorigenesis.Conclusion: RP9P promotes colorectal cancer progression by regulating the miR-133a-3p/FOXQ1 axis.

Afatinib has improved the prognosis of epidermal growth factor receptor-positive advanced non-small cell lung cancer and has been explored in the treatment of human epidermal growth factor receptor 2 (HER2)-amplified breast cancer. However, its clinical efficacy in HER2-amplified endometrial cancer has not been reported. Herein, we present the clinical benefit of afatinib in a case of stage IIIC endometrioid adenocarcinoma refractory to multiple lines of chemotherapy and eventually developed pulmonary, abdominal and pelvic metastasis. Upon referral to our clinic, capture-based targeted sequencing was performed on both blood and tumor samples and revealed HER2 amplification. The patient was administered with afatinib and achieved partial response (PR) after two months of treatment, reflected by a significant reduction in pulmonary lesions and serum levels of tumor markers including carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, 125, 15-3 and cytokeratin 19 fragment antigen 21-1 (CY211). The patient passed away after 3 months of afatinib treatment due to suspected complications of severe intestinal obstruction. Our report demonstrates the efficacy of afatinib in a heavily pre-treated HER2-amplified endometrial cancer patient with multi-organ metastasis. This case also highlights the need to include comprehensive mutational profiling in the standard management of endometrial cancer patients for treatment guidance.

Gastric cancer (GC) is among the malignant cancers with the highest incidence and mortality worldwide. As GC is not very sensitive to current chemotherapy drugs, there is an urgent need to develop new effective drugs. Raddeanin A (RA) is extracted from the traditional Chinese medicine Anemone raddeana Regel, which has an anti-cancer effect. The purpose of this study was to explore the effects of RA on GC in vitro and in vivo. We explored the targets of RA in GC through network pharmacology. MTT assay, flow cytometry, Western blotting, and other methods were used to detect the effects of RA on the proliferation, apoptosis, and autophagy of GC cells. After preconditioning with hydroxychloroquine (HCQ) and rapamycin, we observed the effects of RA-induced autophagy on apoptosis. We further verified the antitumor effect and safety of RA in vivo. Using SNU-1 xenograft tumor model in nude mice, tumor volume was observed and liver toxicity was observed by immunohistochemistry. Many cancer-related signaling pathways were visualized using Cytoscape software. Among them, the MAPK signaling pathway was one of the highest-ranked pathways. The MTT assay results suggested that RA could inhibit the proliferation of HGC-27 and SNU-1 cells effectively. Flow cytometry and Western blotting confirmed that RA could significantly induce apoptosis of HGC-27 and SNU-1 cells. Electron microscopy and Western blotting demonstrated that RA could induce autophagy of HGC-27 and SNU-1 cells. Further experiments suggested that HCQ, an autophagy inhibitor, could enhance the capacity of RA to induce apoptosis. In animal studies, we found that intraperitoneal injection of RA could effectively and safely inhibit gastric tumors. RA significantly inhibited the proliferation and induced autophagy and apoptosis of GC cells. In combination with HCQ, RA-induced apoptosis increased in vitro. The combined application of RA and autophagy inhibitors may serve as an added approach to the treatment of GC, but the underlying mechanism needs further exploration. In vivo, it was observed that RA has a good antitumor effect without increasing liver toxicity.