Jia Feng

KLF15 promotes the proliferation and metastasis of lung adenocarcinoma cells and has potential as a cancer prognostic marker

Lung adenocarcinoma (LADC)is a general form of non-small cell lung cancer that represents a significant threat to public health worldwide. The 5-year-survival rate for LADC is currently below 15%. The transcription factor KLF15, also called kidney-enriched KLF (KKLF), has been proven to play a role in inhibiting proliferation and diversification of carcinoma cells, including those of the endometrium, pancreas and breast, but the involvement of KLF15 in LADC has not previously been studied. In this study, we compared the in vitro expression of KLF15 in human LADC tissues and adjacent normal lung tissues. Expression of KLF15 was found to be abnormally high in LADC tissues and cells compared with adjacent non-tumorous tissues, and was correlated with tumor TNM stage and tumor differentiation (P = 0.003, P = 0.001, respectively). The effect of KLF15 on cell growth and migration were explored in vitro by Western Blotting, CCK8 and colony formation assays, flow cytometry analysis and transwell migration assays, and in vivo by analysis of tumorigenesis in 5-week old BALB/c nude mice. Knockdown of KLF15 significantly upregulated the protein levels of cleaved caspase-3, caspase-7, caspase-8 and PARP, thereby inducing apoptosis. Downregulation of KLF15 in A549 and NCI-H1650 cell lines resulted in these cell lines exhibiting markedly slower growth rates when injected subcutaneously into the flank of nude mice, compared with the comparator control groups (P < 0.05). Collectively, our findings suggest that KLF15 may have a significant effect on LADC cell survival, and that it represents a potential therapeutic and preventive biomarker for LADC prognosis and treatment.

Combination of cadherin-17 and SATB homeobox 2 serves as potential optimal makers for the differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma

BACKGROUND Pulmonary enteric adenocarcinoma (PEAC), a rare type of non-small cell lung cancer, has similar histological and immunohistochemical morphology to colorectal adenocarcinoma. Cadherin-17 (CDH17) and SATB homeobox 2 (SATB2) immunoexpression have recently been demonstrated in colorectal adenocarcinoma. In this study, we evaluated the value of CDH17 and SATB2 in the diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma. METHODS A total of 13 PEAC cases and 27 metastatic colorectal adenocarcinoma cases were enrolled in our cohort study. We analyzed the expressions of CK7, CK20, CDX-2, villin, cadherin-17 (CDH17), and SATB homeobox 2 (SATB2) using immunohistochemistry. Staining intensity and percentage of positive-staining cells were recorded. Sensitivity and specificity values for immunostains, individually and in combination, were computed and compared. RESULTS Combining CDH17 and SATB2 resulted in high sensitivity (76.92%) and specificity (100%). In our study, the use of CK7+, napsin A+, TTF-1+, napsin A+TTF-1+ in combination with CDH17-/SATB2- had a higher area under the curve compared to the combination CDH17-/SATB2-. However, no significant differences were observed between the combination CDH17-/SATB2- and other combinations (P>0.05). CONCLUSIONS In combination, CDH17 and SATB2 serve as potential optimal markers for the differential diagnosis of PEAC and metastatic colorectal adenocarcinoma.Background Pulmonary enteric adenocarcinoma (PEAC), a rare type of non-small cell lung cancer, has similar histological and immunohistochemical morphology to colorectal adenocarcinoma. Cadherin-17 (CDH17) and SATB homeobox 2 (SATB2) immunoexpression have recently been demonstrated in colorectal adenocarcinoma. In this study, we evaluated the value of CDH17 and SATB2 in the diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma. Methods A total of 13 PEAC cases and 27 metastatic colorectal adenocarcinoma cases were enrolled in our cohort study. We analyzed the expressions of CK7, CK20, CDX-2, villin, cadherin-17 (CDH17), and SATB homeobox 2 (SATB2) using immunohistochemistry. Staining intensity and percentage of positive-staining cells were recorded. Sensitivity and specificity values for immunostains, individually and in combination, were computed and compared. Results Combining CDH17 and SATB2 resulted in high sensitivity (76.92%) and specificity (100%). In our study, the use of CK7+, napsin A+, TTF-1+, napsin A+TTF-1+ in combination with CDH17-/SATB2- had a higher area under the curve compared to the combination CDH17-/SATB2-. However, no significant differences were observed between the combination CDH17-/SATB2- and other combinations (P>0.05). Conclusions In combination, CDH17 and SATB2 serve as potential optimal markers for the differential diagnosis of PEAC and metastatic colorectal adenocarcinoma.

Spondin2 is a new prognostic biomarker for lung adenocarcinoma

Spondin 2 (SPON2) is a member of the F-spondin superfamily of genes that encode an extracellular matrix protein. SPON2 has been identified by mRNA differential display screening of cancerous and noncancerous lung cell lines in vitro [1], however, its role in pulmonary adenocarcinoma (ADC) patients remains unclear. In our study, we evaluated whether SPON2 can be used as a biomarker for the diagnosis of pulmonary ADC and any association between SPON2 protein levels and clinicopathological characteristics. Firstly, the mRNA levels of SPON2 in pulmonary ADCs and normal adjacent tissue samples were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 60) assay and the expression of SPON2 protein were detected by tissue microarray immunohistochemistry analysis (TMA-IHC) (n = 280). Overexpression of SPON2 protein in cancerous tissues was associated with the clinical characteristics of ADC patients and their overall survival. Levels of SPON2 mRNA and protein were significantly expressed higher in ADC tissues than in adjacent normal tissues. Finally, through univariate and multivariate regression analysis, we found that overexpression of SPON2 protein levels correlates with differentiation, positive lymph nodes metastasis, higher serum carcinoembryonic antigen (CEA) level and poor overall survival. Overexpression of SPON2 protein is an independent prognostic biomarker in ADC patients. Our data revealed that SPON2 played an oncogene role in ADC development and progression. Inhibiting SPON2 might represent a new strategy for pulmonary ADC.

Expression of Kruppel‑like factor 8 and Ki67 in lung adenocarcinoma and prognosis

Kruppel-like factor 8 (KLF8) belongs to the KLF family and has various roles in the regulation of the cell cycle, proliferation and tumor genesis. KLF8 is overexpressed in gastric, ovarian, breast and renal cancer. Additionally, KLF8 may affect invasion and metastasis of tumors. However, whether KLF8 also acts as an ontogeny in lung adenocarcinoma (LAC) remains unknown. The aim of the present study was to determine the association between KLF8 expression and various clinical and pathological parameters. Western blot assays and immune histochemistry analyses revealed that KLF8 level in LAC tissues was higher than that in the normal lung tissues and KLF8 expression was significantly associated with clinical variables (P<0.05). Kaplan-Meier curves revealed that high expression of KLF8 was related to poor prognosis in patients with LAC. The present study also demonstrated that KLF8 was involved in the progression of lung adenocarcinoma. This data suggested that KLF8 may act as a prognostic factor in lung adenocarcinoma progression.

Lepidic component at tumor margin: an independent prognostic factor in invasive lung adenocarcinoma

Previous studies have proven that the lepidic component of lung adenocarcinoma is an independent prognostic factor and has a favorable effect on patient prognosis; however, no studies have reported the specific distribution of the lepidic component in lung cancer. In this study, we focused mainly on whether the lepidic component at the tumor margin was an independent prognostic factor for invasive lung adenocarcinoma. We reviewed 276 patients with invasive lung adenocarcinomas and divided them into 2 groups-181 with tumors of 3 cm or less and 95 with tumors of greater than 3 cm-to study their histopathologic and clinicopathological characteristics. The long lepidic structure at the tumor margin was designated as the marginal lepidic feature. In the group with tumors of 3 cm or less, the lepidic component and marginal lepidic feature were significantly associated with histologic subtype, TNM stage, and lymph node metastasis (P < .05), whereas in the group with tumors of greater than 3 cm, the lepidic component and marginal lepidic feature were not correlated with histopathologic or clinicopathological characteristics. Furthermore, the patients with tumors of 3 cm or less and marginal lepidic lesions demonstrated significantly longer overall survival than did those without the structure (P < .001). We concluded that the marginal lepidic feature of invasive lung adenocarcinoma is a significant histologic feature that suggests a better prognosis.

miR-335 inhibited cell proliferation of lung cancer cells by target Tra2β

Accumulating evidence has suggested that the dysregulation of miRNA is an important factor in the pathogenesis of lung cancer. Here, we demonstrate that miR‐335 expression is reduced in non‐small cell lung cancer (NSCLC) tumors relative to non‐cancerous adjacent tissues, while the expression of Tra2β is increased. In addition, clinical data revealed that the increased Tra2β and decreased miR‐335 expression observed in NSCLC cells was associated with poor patient survival rates. In vitro experimentation showed that the overexpression of miR‐335 inhibited the growth, invasion and migration capabilities of A459 lung cancer cells, by targeting Tra2β. In contrast, inhibition of miR‐335 or overexpression of the Tra2β target gene stimulated the growth, invasion and migratory capabilities of A459 lung cancer cells in vitro. Furthermore, overexpression of miR‐335 or inhibition of Tra2β decreased the phosphorylation of Rb‐S780 and Rb‐AKT. Overall, these findings suggest that the downregulation of miR‐335 in A459 lung cancer cells promoted cell proliferation through upregulation of Tra2β, mediated via activation of the AKT/mTOR signaling pathway, and suggest that miR‐335 may have potential as a novel therapeutic target for NSCLC.

Ectopic immature renal tissue in gubernaculum associated with undescended testis of a 1-year-old child: A case report

Rationale: Ectopic immature renal tissue (EIRT) is extremely rare in congenital malformations. Moreover, the fundamental pathogenesis of EIRT is still unclear and controversial. Patient concerns: The right scrotum of a 1-year-old man was found empty for a period of 1 month. B-ultrasonography revealed normal bilateral kidneys and a hypoechoic nodule in the right groin. Diagnoses: Based on B-ultrasonography, surgery and pathological examination, we concluded a case of abnormally located and EIRT in the inguinal canal. Interventions: After pathological diagnosis, the patient was not treated with drugs. Outcomes: One year after the operation, the patient recovered. Lessons: EIRT in gubernaculum is extremely rare. Because of the potential risk of malignant transformation, it is necessary to diagnose and treat it early.