OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis.

BACKGROUND: Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied. PATIENTS AND METHODS: Three public CRC gene databases were applied for OLA1 mRNA expression detection. The clinical data of 111 CRC patients were retrospectively collected from the Second Affiliated Hospital of Zhejiang University (SAHZU) for OLA1 protein expression and Kaplan-Meier Survival analysis. OLA1 stably knocked out CRC cell lines were conducted by CRISPR-Cas9 for experiments in vitro and in vivo. RESULTS: OLA1 was highly expressed in 84% CRC compared to matched surrounding tissues. Patients with OLA1 high expression had a significantly lower 5-year survival rate (47%) than those with OLA1 low expression (75%). OLA1 high expression was an independent factor of poor prognosis in CRC patients. OLA1-KO CRC cell lines showed lower ability of growth and tumorigenesis in vitro and in vivo. By mRNA sequence analysis, we found 113 differential express genes in OLA1-KO cell lines, of which 63 were hypoxic related. HIF1α was a key molecule in hypoxic regulation. Further molecular mechanisms showed HIF1α /CA9 mRNA and/or protein levels were heavily downregulated in OLA1-KO cell lines, which could explain the impaired tumorigenesis. According to previous studies, HIF1α was a downstream gene of GSK3ß, we verified GSK3ß was over-activated in OLA1-KO cell lines. CONCLUSION: OLA1 was a new gene that was associated with carcinogenesis and poor outcomes in CRC by activation of HIF1α/CA9 axis, which may be interpreted by GSK3ß.

Clinicopathological features and prognostic value of CD276 expression in female reproductive system malignancies: A meta-analysis.

The relationship between CD276 and malignancies of the female reproductive system has previously been controversial. The purpose of this study was to evaluate the predictive value of CD276 expression in clinicopathological features and prognosis of female reproductive system malignant tumors through meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang databases were searched for studies published up to December 2022 on the role of CD276 expression in the clinicopathological features and prognosis of female reproductive system malignancies. STATA 14.0 was used for meta-analysis. A total of 10 studies were included, involving 840 patients with malignant tumors of the female reproductive system. The results showed that in terms of clinicopathological features: CD276 expression was closely related to lymph node status [OR = 2.33， 95 %CI = 1.32-4.11， P = 0.003], tumor differentiation [OR = 2.15， 95 %CI = 1.27-3.63, P = 0.004], and FIGO stage [OR = 2.58， 95 %CI = 1.44-4.61, P = 0.001] of reproductive system malignant tumors. In terms of prognosis: CD276 expression is strongly associated with shorter OS in patients with female reproductive system malignancies [HR = 3.33, 95 % CI = 1.36-8.15, P = 0.01]. CD276 may be a new target for immunotherapy and a biomarker for predicting poor prognosis of female reproductive system malignancies.

Evaluating overall survival and competing risks of survival in patients with early-stage breast cancer using a comprehensive nomogram.

BACKGROUND: Patients with early-stage breast cancer (BC) live long but have competing comorbidities. This study aimed to estimate the effect of cancer and other causes of death in patients with early-stage BC and further quantify the survival differences. MATERIALS AND METHODS: Data of patients diagnosed with BC between 2010 and 2016 were collected from the Surveillance, Epidemiology, and End Results database. The cumulative incidence function for breast cancer-specific mortality (BCSM) and other cause-specific mortality (OCSM) was estimated, and the differences were tested using the Gray test. The nomogram for estimating 3-, 4-, and 5-year overall survival (OS), breast cancer-specific survival, and other cause-specific survival was established based on Cox regression analysis and Fine and Gray competing risk analysis. The discriminative ability, calibration, and precision of the nomogram were evaluated and compared using C statistics, calibration plots, and area under the receiver operating characteristic curve. RESULTS: A total of 196 304 eligible patients with early-stage BC were identified in this study. Of these, 12 417 (6.3%) patients died: 5628 (45.3%) due to BC and 6789 (54.7%) due to other causes. Five validated variables were incorporated to develop the prognostic nomogram: age, grade, tumor size, subtype, and surgery of primary site (Figure 3). Age was a strong predictive factor, which was more obvious in OCSM. The effect of surgery was more prominent in BCSM. Increased tumor size was correlated with OS and BCSM and slightly correlated with OCSM. Grade and subtype differences were more predominant in BCSM than in OCSM. The established nomogram was well calibrated and displayed good discrimination. CONCLUSIONS: We evaluate OS and competing risks of death in patients with early-stage BC, establishing the first comprehensive prognostic nomogram.

Predictive value of a nomogram for melanomas with brain metastases at initial diagnosis.

BACKGROUND: Estimation of incidence and prognosis of melanomas with brain metastases (MBM) at initial diagnosis based on a large cohort is lacking in current research. This study aims to construct an effective prognostic nomogram for newly diagnosed MBM. MATERIALS AND METHODS: Patients diagnosed with melanomas from Surveillance, Epidemiology, and End Results program between 2010 and 2014 were enrolled in our study. Risk factors predicting brain metastases (BM) were identified using logistic regression analysis. Cox regression analysis was performed to identify prognostic factors of overall survival (OS). Nomogram for estimating 6-, 9-, and 12-month OS was established based on Cox regression analysis. The discriminative ability and calibration of the nomogram were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS: Sixty-two thousand three hundred and sixty-nine melanoma patients were enrolled, including 928 with BM. Sex, marital status, insurance status, subsite, surgery of primary sites, radiation, chemotherapy, bone metastases, liver metastases, and lung metastases were associated with MBM at initial diagnosis. On multivariable Cox regression, the following eight variables were incorporated in the prediction of OS: age, unmarried status, absence of surgery to primary sites or unknown, absence of radiation or unknown, absence of chemotherapy or unknown, with bone metastases, with liver metastases, and with lung metastases. The nomogram showed good predictive ability as indicated by discriminative ability and calibration, with the C statistics of 0.716 (95% CI, 0.695-0.737). CONCLUSIONS: The incidence and prognosis of MBM patients were well estimated in this study based on a large cohort. The nomogram performed well and could be a useful tool to predict prognosis.

[Effect of total anthraquinone in rheum on aquaporin 2 expression in rat distal colon].

OBJECTIVE: To investigate effect of total anthraquinone in rheum on aquaporin 2 expression in rat distal colon. METHOD: SD rats were randomly divided into control group, low dose group, middle dose group and high dose group. Gavaged to control group, and treated group were administered saline and total anthraquinone in rheum with dosage of 0.14, 2.5, 4.5 g x kg(-1) x d(-1), respectively. All rats were put sacrificed after 5 days and stool in full length colon was gently collected to detect water content stool. Distal colon was removed to detect AQP2 expression with immunohistochemistry, western blot and RT-PCR. RESULT: No diarrhea was found in low dose group and control group, there were not significant difference water content of stool and AQP2 expression between low dose group and control group. However, soft feces and loose stools occurred in diarrheic dose group, loose stools and watery stool appeared in high dose group. Stool water content increased in diarrheic dose group and High dose group, expression of AQP2 decreased evidently in these two groups (P < 0.01). CONCLUSION: Total anthraquinone in rheum can reduce the transcription and translation of AQP2 in rats' distal colon, increase fecal water content, which probably is one of the mechanisms of diarrhea caused by total anthraquinone in rheum.

[Occurrence dynamics of migratory pest insects Cnaphalocrocis medinalis and Sogatella furcifera in transgenic Bt rice field in Xing'an County of Guangxi Province].

An investigation was conducted in Xing' an County of Guangxi Province in 2010 to study the occurrence and damage characteristics of two unique migratory pest insects, rice leaffolder (Cnaphalocrocis medinalis) and white-backed planthopper (Sogatella furcifera), in a transgenic Bt rice (cv. HH1 with dual Cry1Ab+Cry1Ac genes) field, taking the corresponding non-transgenic parent (cv. MH63) field as the control. No significant differences were observed in the abundance of C. medinalis eggs and larvae in the two fields, but the percentage of fold-leaf plants and the fold-leaf rate per plant were significantly lower in transgenic Bt rice field than in the control, suggesting that transgenic Bt rice had higher resistance against the target pest insect C. medinalis. As for S. furcifera, its occurrence dynamics of nymphs, adults (including macro- and brachypterous forms), and whole population had no significant differences between the two fields, but the abundance of the nymphs and brachypterous adults at the peak stage of S. furcifera occurrence was obviously higher in transgenic Bt rice field than in the control, while the macropterous abundance was in adverse. The sex ratio of female of the macropterous adults at the late growth stage of rice was generally lower in transgenic Bt rice field than in the control. These results suggested that under the background of large area commercial production of transgenic Bt rice, the occurrence and harm of the non-target pest insect S. furcifera could become more complicated.