Clinicopathological and biomolecular characteristics of stage IIB/IIC and stage IIIA colon cancer: Insight into the survival paradox

Abstract

Background A survival paradox of stage IIB/IIC and IIIA colon cancer has been consistently observed throughout revisions of the TNM system. This study aimed to understand this paradox with clinicopathological and molecular differences. Methods Clinicopathological characteristics of patients with pathologically confirmed stage IIB/IIC or IIIA colon cancer were retrospectively reviewed from a database. Publicly available molecular data were retrieved, and intrinsic subtypes were identified and subjected to gene sets enrichment analysis (GSEA). Results Among the 159 patients included in the clinicopathological analysis, those at stage IIB/IIC had worse 3‐year disease‐free and overall survival than those at stage IIIA (59.3% vs 91.7%, P < 0.001 and 82.7% vs 98.5%, P < 0.001, respectively), even after adjusting for confounding factors. Data of 95 patients were retrieved from public databases, demonstrating a higher frequency of the microsatellite instable subtype in stage IIB/IIC. The consensus molecular subtype distribution pattern differed between the groups. The GSEA further suggested the protumor inflammatory reaction might be more prominent in stage IIB/IIC. Conclusions The survival paradox in colon cancer was confirmed and appears to be a multifactorial phenomenon not attributed to a single clinicopathologic factor. However, the greater molecular heterogeneity in stage IIB/IIC could contribute to the poor prognosis.

Preoperative Hepatic and Regional Arterial Chemotherapy in Patients Who Underwent Curative Colorectal Cancer Resection

“…It should be noted that the DFS rates of the control arm in our trial were poorer than previous trials of oxaliplatin-based chemotherapy, which is likely due to different prognostic factors for baseline characteristics, and there were more T4 patients in our trial (61% in our trial compared with 19% in the MOSAIC trial and 2% in the NSABP C-07 trial) 16,17 . Previous studies showed that patients with stage IIB/C (T4N0) colon cancer had significantly worse oncologic outcomes than those with stage IIIA (T1-2N1) colon cancer regardless of adjuvant chemotherapy 18–20 …”

Identification prognosis-associated immune genes in colon adenocarcinoma

“…SLC10A2, FABP4, ADIPOQ, and INHBA involved in lipid transport and lipid localization BPs [ 44–46 ]; INHBA, CXCL3, and NGFR participate in the regulation of the cytokine–cytokine receptor interaction pathway; FABP4 and ADIPOQ involved in the regulation of PPAR signaling pathway, which coincided with the previous report, PPAR signaling pathway might affect the recurrence of COAD patients [ 47 , 48 ]. The GSEA analysis further suggested that the pro-tumor inflammatory reaction might be more prominent in stage IIB/IIC of COAD [ 49 ]. The blockade of PD-L1 increased FABP4 expression in tissue-resident memory T (Trm) cells, promoting lipid uptake by Trm cells [ 50 ].…”

Tissue-Infiltrating Lymphocytes as a Predictive Factor for Recurrence in Patients with Curatively Resected Colon Cancer: A Propensity Score Matching Analysis

“…However, patients with stage IIB or IIC disease have poorer outcomes than those with stage IIIA disease. Therefore, factors other than the previously used T stage and N stage are consid-ered to determine outcomes [18]. Stage II disease was diagnosed in about 30-40% of patients who underwent surgery for colon cancer [19].…”