Expression of Wnt-Related Long Non-coding RNAs ITGB2-AS1, HNF1A- AS1, and Lnc-MAP6-1:3 in Patients with Colorectal Cancer

Colorectal cancer, a disease affecting the colon and rectum, remains one of the most common and deadly forms of cancer worldwide. While doctors have made significant strides in screening and treatment, the disease continues to claim many lives, particularly because it is often detected too late. To improve outcomes, scientists are searching for better ways to spot the disease early by looking for specific molecular signals inside the body. One promising area of research focuses on long non-coding RNAs. These are strands of genetic material that are longer than 200 building blocks but do not contain instructions for making proteins. Instead of building cellular machinery, they act as regulators, turning other genes on or off and influencing how cells grow, divide, and move. In healthy bodies, these regulators work in balance, but in cancer, their activity often goes haywire, helping tumors to form and spread.

A central player in this biological drama is a signaling pathway known as Wnt. Under normal conditions, this pathway helps control cell growth and tissue repair. However, in colorectal cancer, this system often becomes stuck in the "on" position, driving cells to multiply uncontrollably. Because long non-coding RNAs can influence this pathway, researchers suspect that specific ones might serve as reliable markers to identify the disease. If scientists can find which of these RNA strands are present in high or low amounts in cancer patients compared to healthy people, they could potentially develop new, more accurate diagnostic tools. This is the precise question a team of researchers from several universities in Iran set out to answer.

The researchers focused their investigation on three specific long non-coding RNAs that are linked to the Wnt pathway: ITGB2-AS1, HNF1A-AS1, and Lnc-MAP6-1:3. To see how these molecules behaved in the context of colorectal cancer, the team collected tissue samples from thirty patients who had undergone surgery to remove their tumors. For each patient, they gathered two samples: one from the cancerous tumor itself and another from the healthy tissue right next to it. This paired approach allowed them to make a direct comparison, ensuring that any differences they found were due to the cancer rather than natural variations between different people. The team carefully extracted the genetic material from these tissues, converted it into a form that could be measured, and then used a sensitive testing method to count how much of each RNA was present.

The results revealed a clear distinction between the healthy and cancerous tissues for two of the three molecules they studied. The first molecule, ITGB2-AS1, was found to be present in dramatically higher amounts in the tumor tissues. In fact, the cancerous samples contained roughly thirteen times more of this RNA than the healthy samples did. The second molecule, HNF1A-AS1, also showed a significant increase in the tumors, appearing in much higher quantities than in the normal tissue. The third molecule, Lnc-MAP6-1:3, told a different story. While it appeared slightly more common in the tumor samples, the difference was not large enough to be considered statistically significant, meaning it could have happened by chance. This suggests that while the first two molecules are strongly linked to the presence of the cancer, the third one may not play a major role in this specific disease, at least not in the way the researchers expected.

Beyond simply counting the molecules, the team wanted to know if these findings could be useful for diagnosing the disease in a clinical setting. They used a statistical method to test how well the levels of these RNAs could distinguish between a patient with cancer and one without. The results showed that ITGB2-AS1 was an excellent candidate for this purpose. Its levels were so distinct between the two groups that it could correctly identify the disease with high accuracy, acting as a strong signal that the cancer was present. HNF1A-AS1 also performed well, offering a moderate level of accuracy, while Lnc-MAP6-1:3 did not provide a clear enough signal to be relied upon for diagnosis in this group of patients.

These findings add to the growing body of evidence that specific long non-coding RNAs are deeply involved in the development of colorectal cancer. The study confirms that ITGB2-AS1 and HNF1A-AS1 are significantly overactive in tumor tissues, supporting the idea that they could serve as valuable tools for early detection. However, the researchers are careful to note that their work is just the beginning. Because the study involved a relatively small number of patients from a single region, the results need to be confirmed in larger, more diverse groups of people before they can be used in hospitals. Furthermore, while the study measured the amounts of these molecules, it did not explore exactly how they cause the cancer to grow. Future research will need to uncover the specific mechanisms these RNAs use to influence the Wnt pathway and to determine if they can be detected in blood tests, which would make them even more practical for widespread screening. For now, the study provides a clear and encouraging signal that these molecular markers are worth watching as science moves toward better ways to fight colorectal cancer.