Colorectal cancer is the third high-incidence of malignant tumors in the world, and also a kind of tumor with good biological behavior and good efficacy. Colorectal cancer heterogeneity is a very important trait of its biological behavior, which can be reflected in many different aspects, including tumor type, pathogenesis, molecular phenotyping and time-space heterogeneity. Different pathogenesis produces different tumor phenotypes, which are generated in the process of natural evolution and intervention. Various phenotypes show the difference among different individuals of colorectal cancer, in terms of clinical characteristics, treatment response and prognosis. Understanding the heterogeneity of colorectal cancer has important clinical value for individualized treatment.

Colorectal cancer is one of the most common malignant tumors in the world, threatening human health. The treatment strategy of stage II and stage III colorectal cancer has changed from surgery alone to multidisciplinary mode emphasizing perioperative treatment. The indication of adjuvant chemotherapy for stage II colon cancer is still defined by high-risk factors, but only microsatellite status and BRAF gene mutation can help predict efficacy of chemotherapy. Combined chemotherapy is the main adjuvant therapy for stage III colon cancer. The recommended course of adjuvant chemotherapy is 6 months. Based on the results of the IDEA study, the three-month CapeOX regimen (oxaliplatin and capecitabine) is recommended for the treatment of patients with T1-3 and N1 tumors. Neoadjuvant chemotherapy for locally advanced colon cancer is still in the exploratory stage of clinical trials. The difference between the treatment of rectal cancer and colon cancer lies in the application of radiotherapy. Chemoradiotherapy combined with TME (total mesorectal excision) surgery and adjuvant chemotherapy has become the standard treatment for locally advanced rectal cancer. Nowadays, the research hotspots in neoadjuvant therapy of rectal cancer include neoadjuvant chemotherapy and total neoadjuvant therapy (TNT). This article will review the progress of perioperative treatment for colorectal cancer.

OBJECTIVETo investigate the differences of clinical characteristics and molecular features among colorectal cancer subsides and provide evidence for colorectal cancer protection, diagnosis and treatment.

METHODSAll of 4 316 colorectal patients from Shanghai cancer center were selected for clinical character analysis, among which, 2 224 subjects for molecular feature analysis. Clinic pathological characteristics like age, gender, tumor types, histological types, differentiation and T-stage, as well as molecular features like hMLH1, hMSH2, CD44, p21, p53, COX2,E-cadherin, Her2 and Ki-67, were involved into this research.

RESULTSIt showed that compared with left-sided colon and rectal cancers, right-sided cancers occurred more in women (46.0% (541/1 176); 39.2% (424/1 083); 41.2% (848/2 057), respectively, χ² = 11.85, P < 0.01), had more mucinous or signet-ring carcinoma (12.0% (128/1 064), 5.8% (56/960), 4.0% (75/1 859), respectively, χ² = 31.27, P < 0.01), poor differentiated carcinoma (32.1% (343/1 069), 19.5% (201/1 033), 19.3% (380/1 967), respectively, χ² = 72.66, P < 0.01) , and advanced T stage (87.9% (992/1 129), 83.2% (869/1 045), 72.2% (1 486/2 057), respectively, χ² = 121.44, P < 0.01). Meanwhile, the rates of hMLH1 were higher in right-sided colon cancers when compared with rectal cancers (13.4% (59/439) vs 8.5% (88/1 035), OR (95%CI): 1.67 (1.18-2.37)), as well as the rates of hMSH2 negative expression (4.9% (22/452) vs 2.4% (26/1 083), OR (95% CI): 2.08(1.17-3.71)). The rates of p53 positive expression were higher in right-sided colon cancers when compared with rectal cancers (76.2% (321/421) vs 68.4%, (776/1 134), OR (95% CI): 0.68 (0.52-0.87)). Compared with right-sided colon cancers, the rates of Her2 positive expression were higher in rectal cancers (19.3% (176/913) vs 13.2% (45/340), OR (95% CI): 1.57 (1.10-2.23)) , as well as the rates of Ki-67 expression which was positive in more than 50% cells (73.6% (840/1 141) vs 65.6% (299/456), OR (95% CI): 0.68 (0.54-0.86)).

CONCLUSIONThere are specific characteristics in right-sided colon cancers. The difference of molecular features between right-sided colon and rectal cancers are more significant.

Adenocarcinoma, Mucinous ; Cadherins ; Carcinoma ; Carcinoma, Signet Ring Cell ; China ; Colonic Neoplasms ; Colorectal Neoplasms ; Female ; Humans ; Neoplasm Grading ; Neoplasm Staging ; Rectal Neoplasms ; Sex Factors

Objective To investigate the effects of different culture conditions(RPMI-1640,DMEM and DMEM/F12 medium)on the passage of MPM cells isolated from the tissues of Malignant pleural mesothelioma(MPM),and to study the effects of CDKN2B on the proliferation,invasion and apoptosis of MPM cells.Methods MPM cells were isolated from MPM tissues and cultured in RPMI-1640,DMEM and DMEM/F12 medium,respectively.Cell proliferation was examined by CCK-8,and the nuclei and chromosomes were observed by Wright-Giemsa staining.Fluorescence intensities of Calretinin,CD141,CK5,EMA and WT-1 were conducted by immunofluorescence assay.The mRNA and protein expression of CDKN2B were detected by RT-qPCR and Western blot,respectively.Transwell was used to detect cell invasion and flow cytometry was used to detect cell apoptosis.Results The established MPM cells showed good viability when passaged to the 10th generation in RPMI-1640,DMEM and DMEM/F12 cultures,and the MPM markers Calretinin,CD141,CK5,EMA and WT-1 were all expressed in the cells.The viability of MPM cells in RPMI-1640 culture medium was relatively stable.CDKN2B was downregulated in MPM cells(P<0.05),and overexpression of CDKN2B significantly suppressed the proliferation(P<0.05),invasion(P<0.05)and epithelial interstitial transformation of MPM cells(P<0.01),and promoted the apoptosis(P<0.01).Conclusion The established MPM cells were stably passaged in RPMI-1640 culture medium,and CDKN2B may be a potential target for the diagnosis and treatment of MPM.

Objective:To develop and validate a radiomics biomarker for the preoperative estimation of the tumor-stroma ratio (TSR) in rectal cancer.Methods:From January 2016 to March 2019, totally 149 patients with rectal cancer were enrolled retrospectively at Fudan University Shanghai Cancer Center. The patients were divided into two cohorts using a random number table, 119 in the training and 30 in validation cohorts. The patients were classified into the TSR-high group (TSR>50%) and TSR-low group (TSR≤50%) according to the content of tumor stroma in pathology. All patients underwent T 2WI, enhanced T 1WI and DWI. The lesions on the T 2WI, enhanced T 1WI, DWI and ADC images were delineated and radiomics features were extracted. A radiomics signature (rad-score) was generated by using the least absolute shrinkage and selection operator (LASSO) algorithm. The Spearman correlation coefficients were used to determine the association between rad-score and TSR. The area under the ROC curve (AUC) was used to assess the diagnostic performance of the rad-score. The reliability of the rad-score was quantified by calculating the sensitivity, specificity and accuracy of TSR. Results:With LASSO, a rad-score with 13 radiomics parameters was successfully constructed and was positively correlated with TSR score in the training ( r=0.72, P<0.001) and validation cohorts ( r=0.46, P=0.011). In the training cohort, the AUC of the rad-score was 0.940, with the sensitivity, specificity, accuracy of 100%, 87.3%, 92.4%. In the validation cohort, the AUC was 0.796, with the sensitivity, specificity, accuracy of 83.3%, 67.7%, 73.3%. Conclusions:The rad-score is of promising value for TSR estimation in rectal cancer. It is a promising supplement for patient stratification and may inform decision-making.