These authors contributed equally to this workPurpose: This study aimed to evaluate the role of colony-stimulating factor 2 (CSF2) in chemotherapy resistance, prognosis, and immune response and to identify its possible mechanisms underlying drug resistance. Methods: Drug-resistant cell lines were obtained by successively increasing drug concentration. RNA-Seq was performed to screen hub genes. CSF2 expression was analyzed via immunohistochemistry. Moreover, The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) dataset, and R2 platform were used to explore the correlations among CSF2 expression, prognosis, and immune response. Results: RNA-Seq indicated that microRNAs in cancer, P53 signaling pathway, and cell cycle were associated with FOLFOX chemotherapy resistance. Protein-protein interaction (PPI), molecular complex detection (MOCDE), and qRT-PCR analysis verified CSF2 as the hub gene in chemotherapy resistance. Moreover, CSF2 expression was lower in the normal tissue than in the cancerous tissue (P<0.05). Higher expression of CSF2 was associated with poor OS and DFS in colon cancer patients (P<0.05). We further found similar results in the Oncomine database and R2 platform (P<0.05). A higher expression of CSF2 in the CRC tissue may be caused by demethylation, which was verified using the TCGA datasets. Moreover, GSEA demonstrated that CSF2 was associated with immune response, which was consistent with results reported using TIMER datasets. Conclusion: CSF2 is a novel biomarker and a prognostic factor for the survival of CRC patients affecting the immune response, and an overexpression of CSF2 in CRC patients may be caused by DNA demethylation.

Purpose This study aimed to identify the risk factors associated with performing a difficult laparoscopic radical resection of rectal cancer, and to establish a predictive nomogram to help individual clinical treatment decisions. Methods A total of 977 patients with rectal cancer who underwent laparoscopic radical resection between January 2014 and December 2016 were enrolled in this study. The difficulty of laparoscopic-assisted rectal resection (LARR) was defined according to the scoring criteria reported by Escal. A logistic regression analysis was performed to identify the variables that may affect the difficulty of LARR, and a nomogram predicting the surgical difficulty was created. Results A multivariate analysis demonstrated that a BMI > 28 kg/m 2 , the distance between the tumor and the anal margin ≤ 5 cm, the maximum transverse tumor diameter > 3 cm tumor, interspinous distance < 10 cm, history of abdominal surgery, and preoperative radiotherapy were independent risk factors and they were, therefore, included in the predictive nomogram for identifying a difficult LARR. Conclusions This study defined a difficult LARR and identified independent risk factors for a difficult operation and created a predictive nomogram for difficult LARR. This nomogram may facilitate the stratification of patients at risk for being associated with a difficult LARR for rectal cancer.

Aim Laparoscopic total mesorectal excision (LaTME) following preoperative chemoradiotherapy (PCRT) in locally advanced rectal cancer (LARC) is technically demanding. The present study is intended to evaluate predictive factors of surgical difficulty of LaTME following PCRT by using pelvimetric and nutritional factors. Method Consecutive LARC patients receiving LaTME after PCRT were included. Surgical difficulty was classified based upon intraoperative (operation time, blood loss, and conversion) and postoperative outcomes (postoperative hospital stay and morbidities). Pelvimetry was performed using preoperative T2-weighted MRI. Nutritional factors such as albumin-toglobulin ratio (AGR) and prognostic nutritional index (PNI) were calculated. Multivariable logistic analysis was used to identify predictors of high surgical difficulty. A predictive nomogram was developed and validated internally. Results Among 294 patients included, 36 (12.4%) patients were graded as high surgical difficulty. Logistic regression analysis demonstrated that previous abdominal surgery (OR = 6.080, P = 0.001), tumor diameter (OR = 1.732, P = 0.003), intersphincteric resection (vs. low anterior resection, OR = 13.241, P \ 0.001), interspinous distance (OR = 0.505, P = 0.009), and preoperative AGR (OR = 0.041, P = 0.024) were independently predictive of high surgical difficulty of LaTME after PCRT. Then, a predictive nomogram was built (C-index = 0.867). Conclusion Besides previous abdominal surgery, type of surgery (intersphincteric resection), tumor diameter, and interspinous distance, we found that preoperative AGR could be useful for the prediction of surgical difficulty of LaTME after PCRT. A predictive nomogram for surgical difficulty may aid in planning an appropriate approach for rectal cancer surgery after PCRT.

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