Background The status of targeted genes and the association between targeted genes and clinicopathological features in Chinese lung cancer patients remains to be elucidated. Methods The status of 10 targeted genes was evaluated by next‐generation sequencing (NGS) in 884 non‐small cell lung cancer (NSCLC) patients. The relationship between gene alterations and clinicopathological characters was analyzed. Results Overall, 684 (77.4%) patients harbored gene alterations, and EGFR (510, 57.7%) was found to be the most common type of mutation followed by KRAS (91, 10.3%), HER2 (38, 4.3%), PIK3CA (32, 3.6%), ALK (21, 2.4%), BRAF (10, 1.1%), ROS1 (5, 0.6%), RET (5, 0.6%), MET (4, 0.5%) and NRAS (1, 0.1%). Gene alterations were more frequent in females, non‐smokers and adenocarcinoma (P < 0.001). EGFR mutations were associated with women, non‐smokers, normal level of serum tumor markers, and adenocarcinoma (P < 0.001). Patients without lymph node metastasis (P = 0.012), or early stage disease (P < 0.001) exhibited a higher EGFR mutation rate. KRAS mutations tended to arise in men (P < 0.001), smokers (P < 0.001) and patients with higher levels of serum tumor markers (P = 0.048). A mucus‐producing component was associated with KRAS (P < 0.001), ROS1 (P = 0.033) and ALK (P < 0.001) alterations. ALK and ROS1 rearrangements were more frequent in micropapillary structures (P = 0.004, P = 0.012). BRAF mutation was associated with advanced disease patients and micropapillary structure (P < 0.001). PIK3CA mutation was more likely to be found in elderly patients (P = 0.014). Some patients had synchronous gene alterations, including EGFR/PIK3CA, EGFR/HER2, HER2/KRAS, EGFR/KRAS, EGFR/ROS1, EGFR/NRAS, KRAS/PIK3CA, KRAS/PIK3CA/HER2. Conclusions Most patients had at least one genetic alteration, and individual patients harbored synchronous mutation. Each gene alteration had unique clinicopathological characteristics. Key points Significant findings of the study This study revealed the frequency and distribution of 10 targeted gene abnormalities and their association with clinicopathological parameters of Chinese non‐small cell lung cancer (NSCLC) patients in eastern China. What this study adds Some rare synchronous mutations were detected in our study by next‐generation sequencing (NGS).

Background: Suppressor anaphase-promoting complex domain containing 2 (SAPCD2) is a novel gene playing important roles in the initiation, invasion, and metastasis of several malignancies. However, its role in colorectal carcinoma (CRC) still remains unclear. Method: In this study, we investigated the expression and biological function of SAPCD2 in CRC. Immunohistochemistry (IHC) for SAPCD2 was performed in 410 pairs of CRC specimens and corresponding normal epithelial tissues, and in 50 adenoma tissues. Clinical pathological factors were analyzed in relation to the expression of SAPCD2. The biological functions of SAPCD2 in CRC cells and its effect on cell cycle were investigated in vitro and in vivo through gain/loss-of-function approaches. Results: IHC showed that SAPCD2 expression was significantly higher in CRC tissues compared to adenoma and normal epithelium tissues and was correlated with tumor location (p = 0.018). SAPCD2 significantly promoted cell proliferation, migration, and invasion both in vitro and in vivo (p < 0.05). In addition, SAPCD2 knockdown in CRC cells was associated with reduced G 1 /S transition, while overexpression caused G 2 /M phase arrest (p < 0.05). Conclusions: In sum, SAPCD2 is overexpressed in CRC tissues and plays a critical role in CRC progression. Therefore, it might represent a promising therapeutic target for CRC treatment.

Colorectal cancer (CRC) has become a major health concern in China due to its increasing incidence and mortality. This study aimed to clarify the relationship between tumor locations and the clinicopathological molecular marker features in eastern China CRC patients. We continuously collected data on 2,356 CRC patients who underwent surgical resection from January 2017 to April 2019. Right-sided colorectal cancer (RCC), was located from the cecum to the transverse colon and left-side colorectal cancer (LCRC) was located from the splenic flexure to the rectum. The clinicopathological indices (including age, sex, pTNM stage, mucinous production, and distant metastasis) and frequency of molecular markers such as KRAS, NRAS, BRAF, and microsatellite instability (MSI) were statistically analyzed between the RCC and LCRC groups. The associations between clinicopathological characters and molecular markers were also investigated. LCRC and RCC proportions in eastern China CRC patients were 81.75% and 18.25%, respectively. RCC (vs. LCRC) was more frequently observed with higher frequencies of MSI-high (MSI-H) and BRAF mutations in female and younger patients, and was closely associated with metastasis, poor differentiation, and mucinous tumors. Tumor location also showed significant differences in bowel wall infiltration degree and pTNM stage. Mutation rates of KRAS, NRAS, MSI, and BRAF were 40.15%, 3.85%, 6.31%, and 2.30%, respectively. Patients with a KRAS mutation tended to be female, had mucinous, perineural invasive, and polypoid tumor. Those with NRAS mutation tended to develop well-differentiated ulcerative tumors. The BRAF mutation was more relevant with lymph node involvement, deeper infiltration of the bowel wall, mucinous, poorly-differentiated tumor with thrombus, and perineural invasion. Furthermore, MSI-H was more commonly found in younger patients with deeper bowel wall infiltration and a poorly-differentiated polypoid tumor, whereas MSS patients tended to develop lymph node involvement, and a mucinous and perineural invasive tumor. In our study, we found that LCRC and RCC showed different features on the clinicopathological and molecular markers in eastern China CRC patients. Since our data differ from those of Western countries and other

ObjectivesTo investigate the frequency and prognostic role of deficient mismatch repair (dMMR) and RAS mutation in Chinese patients with colorectal carcinoma.MethodsClinical and pathological information from 813 patients were reviewed and recorded. Expression of mismatch repair proteins was tested by immunohistochemistry. Mutation analyses for RAS gene were performed by real-time polymerase chain reaction. Correlations of mismatch repair status and RAS mutation status with clinicopathological characteristics and disease survival were determined.ResultsThe overall percentage of dMMR was 15.18% (121/797). The proportion of dMMR was higher in patients <50 years old (p < 0.001) and in the right side of the colon (p < 0.001). Deficient mismatch repair was also associated with mucinous production (p < 0.001), poor differentiation (p < 0.001), early tumor stage (p < 0.05) and bowel wall invasion (p < 0.05). The overall RAS mutation rate was 45.88%, including 42.56% (346/813) KRAS mutation and 3.69% (30/813) NRAS mutation (including three patients with mutations in both). KRAS mutation was significantly associated with mucinous production (p < 0.05), tumor stage (p < 0.05) and was higher in non-smokers (p < 0.05) and patients with a family history of colorectal carcinoma (p < 0.05). Overall, 44.63% (54/121) dMMR tumors harbored KRAS mutation, however, dMMR tumors were less likely to have NRAS mutation. Moreover, dMMR, KRAS and NRAS mutation were not prognostic factors for stage I–III colorectal carcinoma.ConclusionsThis study confirms that the status of molecular markers involving mismatch repair status and RAS mutation reflects the specific clinicopathological characteristics of colorectal carcinoma.

Background: Identification of genomic markers using NGS (next generation sequencing) technology would be valuable for guiding precision medicine treatments for pancreatic cancers. Traditional somatic mutation methods require both tumor and matched non-tumor samples. However, only tumor samples are available in most times, especially in retrospective studies. In this study, we tried to analyze the associations between clinical features and oncogenic somatic mutations in genome-wide from tumor-only samples. Method: 54 tumor-only samples derived from pancreatic cancer patients were used for whole-exome sequencing. An approach involving SNP filtering of variants included in Catalogue of Somatic Mutations in Cancer (COSMIC) database was used to identify oncogenic somatic mutations. The relationships between oncogenic mutations and clinical features were analyzed and simultaneously compared with those from the TCGA database. Results: By analyzing the mutations from tumor only samples, divergent mutation profiles were observed in different locations (head vs body/tail) of pancreatic tumors. The divergences between pancreatic head and body/tail cancers were also confirmed by the TCGA data. Furthermore, mutations of several genes were found significantly associated with clinical features, such as pathological stage and the degree of tumor differentiation. Conclusion: The results confirmed the efficiency of our approach for identifying oncogenic somatic mutations from tumor only samples and revealed the associations between somatic mutations and clinical features in pancreatic cancer.