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Background: Src homology region 2 domain‐containing phosphatase 2 (SHP2) is a novel target for Kirsten rat sarcoma oncogene (KRAS) mutant cancer. We retrospectively studied the significance of SHP2 in KRAS mutant non‐small cell lung cancer (NSCLC) treated with immunotherapy and its relationship with tumor microenvironment (TME). Methods: Sixty‐one advanced KRAS mutant NSCLC patients who underwent immunotherapy were enrolled. Next‐generation sequencing (NGS) was used to profile mutation status. The expression of SHP2, phospho‐SHP2 (pSHP2), and programmed death ligand 1 (PD‐L1) were analyzed by immunohistochemistry (IHC). Quantitative multiplexed immunofluorescence cytochemistry (mIFC) analysis was conducted to describe the TME. Results: SHP2 was heterogeneously expressed in 32 samples in both tumor cells and immune cells and highly expressed (H‐score >10) in 25 (78.1%) samples. The expression levels of SHP2 and pSHP2 were positively correlated. Stromal SHP2 (s‐SHP2) was higher in tumors with PD‐L1 ≥50% versus PD‐L1 <50% (p = 0.039). By quantitative mIFC analysis, the expression of s‐SHP2 had positive correlation with CD8, CD4, CD68, and PD‐L1 levels in stromal area. Patients with high SHP2 expression made up 100.0% of the partial respond (PR) and 80.0% of the stable disease (SD), whereas 50.0% of the progress disease (PD). High SHP2 expression was associated with longer progression‐free survival (PFS) and overall survival (OS) (p < 0.001, p = 0.013). Patients with high expression of both SHP2 and PD‐L1 had longer PFS (p < 0.001). Conclusion: High SHP2 expression could predict the efficacy of immunotherapy and better survival in advanced KRAS mutant NSCLC. SHP2 may function in both tumor cells and immune cells, warranting further study on the potential diverse effects of SHP2 inhibition in TME. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the leading types of cancer that lead to mortalities in the male and female populations. The existing lung cancer-specific markers are not able to accurately predict the condition of the disease, and the response of these markers can vary under various pathological conditions. The ability for tumors to regenerate following treatment can be more aggressive, and this may be due to the remaining lung cancer-specific stem cells, which are resistant to chemotherapeutic drugs. Evaluating cancer stem cells under various pathological conditions, as well as prior and subsequent to treatment, can help to increase the understanding of the underlying mechanisms. In the present study, a mouse model with initial and advanced forms of lung cancer was developed using tobacco smoke carcinogen. It was observed from tissue sections that there were many actively dividing cells spread throughout the mouse lung tissue with the initial stages of lung cancer, and these cells aggregated in advanced stages of lung cancer. Furthermore, immunohistochemical staining indicated that there was an increased number of octamer-binding protein 4 (Oct-4)-positive cells present in mouse tissues with advanced stages of the disease compared with tissues without lung cancer or at the initial stages of disease. The cancer stem cell population following salirasib treatment was also investigated in two groups. The mice in the early treatment group were administered with salirasib following 1 month of tumor growth, and the delayed treatment group was treated following 2 months of tumor growth. The number of cancer stem cells was markedly reduced in the early treatment group. However, salirasib failed to have any observable effect in the delayed treatment group. Cancer stem cells were analyzed using the marker Oct-4 to improve an understanding of the proliferative ability of cancer stem cells under various pathological conditions, which may lead to the development of novel cancer therapeutics.

Apoptosis-related molecules can be abnormally expressed in cancers and underscore the hallmark of resisting cell death in cancer cells. This study was aimed to observe the expression patterns of apoptosis-related molecules in lung cancer and paired non-cancerous tissues, and to observe if there is a correlation between the expression of these apoptotic molecules and clinicopathologic parameters. Immunohistochemistry (IHC) was performed to analyze the expression level of CASP3, CASP8, CASP9, PARP1, Cleaved CASP3 (C-CASP3), Cleaved PARP1 (C-PARP1), XIAP, BIRC5 (Survivin) and BCL2 in lung cancer and paired non-cancerous tissues. We found that apoptosis-related molecules CASP3, CASP9, BCL2, BIRC5 and PARP1 are abnormally expressed in lung cancer cells and their expression were correlated with histology. BCL2, BIRC5 and PARP1 are expressed at higher levels in SCC than in non-SCC. C-PARP1 expression might be an independent prognostic factor for NSCLC.

Objective: To explore the effects of harmful factors in tank cabins on renal function of tank crews., Methods: One hundred and fifty two tank crews as the observation group and 37 soldiers without tank environment exposure as control group were selected in the study. α1-microglobulin(α1-MG), β2-microglobulin(β2-MG), IgG, N-acetyl-β-glucosidase (NAG) and urinary albumin excretion rate (UAER) in morning and 24 h urine were measured., Results: Compared to the control group, the levels of α1-MG, β2-MG, NAG, UAER in observation group were increased significantly (P < 0.05). β2-MG, NAG, UAER of Soldiers with more than 50 motorized hours in observation group were significantly higher than those of control group (P < 0.05). β2-MG, NAG and UAER of soldiers divorced from tank occupation more than 3 years decreased to the normal levels. β2-MG of soldiers divorced from tank occupation more than 10 years was significantly higher than that of 6-10 years group., Conclusion: Tank occupational exposure influences the renal function of tank crews but not to a degree of clinical kidney disease. The renal function of crews divorced from tank occupation may recover but dysfunction of renal tubular reabsorption still exists.